III INTERNATIONAL CONFERENCE ON ACQUIRED IMMUNODEFICIENCY SYNDROME (AIDS) June 1-5, 1987 Washington Hilton and Towers Washington, D.C. The purpose of the conference is to review and exchange information on AIDS epidemiology, virology, molecular biology, immunology, serology, hematology, animal models, neurological implications, neu- ropsychiatric aspects, oncology, diagnostic tests, clinical manifestations, behavioral and addiction aspects, public health, ethical and psychosocial implications, and prevention and control strategies. Sponsored by the: U.S. Department of Health and Human Services Public Health Service National Institutes of Health Alcohol, Drug Abuse, and Mental Health Administration Centers for Disease Control Food and Drug Administration Health Resources and Services Administration and the World Health Organization CONFERENCE COMMITTEES Steering Committee James B. Wyngaarden, National Institutes of Health Paul D. Parkman, Food and Drug Administration David N. Sundwall, Health Resources and Services Administration James 0. Mason, Centers for Disease Control Donald 1. Macdonald, Alcohol, Drug Abuse, and Mental Health Administration ' '~ Jonathan Mann, World Health Organization Organizing Committee George J. Galasso, Chairman, National Institutes of Health Kenneth Bridbord, Co-Chairman, Fogarty International Center, National Institutes of Health Peter J. Fischinger, National Cancer Institute, National Institutes of Health '5 John R. La Montagne, National Institute of Allergy and Infectious Diseases, National Institutes of Health Amoz I. Chernoff, National Heart, Lung, and Blood Institute, National Institutes of Health Gerald V. Quinnan, Food and Drug Administration Peter Bridge, Alcohol, Drug Abuse, and Mental Health Administration Samuel C. Matheny, Health Resources and Services Administration Walter R. Dowdle, Centers for Disease Control Gary R. Noble, Public Health Service Scientific Program Committee H.J. Alter, USA D. Armstrong, USA H. Bachmayer, Austria L. Barbosa, USA K. Bart, USA C. Bartholomew, Trinidad WA. Blattner, USA _ D.T. Bolognesi, USA S. Broder, USA J .B. Brunet, France A. Burny, Belgium L. Chieco-Bianchi, Italy J. Chin, Switzerland J .W. Curran, USA G. de The, France D. Des Jarlais, USA R.C. Desrosiers, USA F. Deinhardt, West Germany M. Donoghue, USA G.R. Dreesman, USA P. Ebbesen, Denmark M. Essex, USA A.S. Fauci, USA A. Fisher, USA R.C. Gallo, USA A.J. Georges, Central African Republic G. Giraldo, Italy J .C. Gluckman, France C. Grady, USA J. Graham, USA I.D. Gust, Australia J. Harris, USA W.A. Haseltine, USA D. Henderson, USA E.M. Hersh, USA J.C. Hill, USA Y. Hinuma, Japan M.S. Hirsch, USA C. Hostetter, USA G. Hunsmann, West Germany H.W. Jaffe, USA J. Jaffee, USA W.F.H. Jarrett, Scotland J .G. Joseph, USA W. Koff, USA H. Koprowski, USA K. Krohn, Finland H.C. Lane, USA R. Lanman, USA T. Lee, USA J. Leikola, Finland S.J. Lengel, USA P.H. Levine, USA J .A. Levy, USA M.A. Martin, USA H. Masur, USA C.R. McCarthy, USA L. Montagnier, France J. Mosley, USA T. Muyembe, Zaire G. Nemo, USA B. Oberg, Sweden G. Papaevangelou, Greece J .W. Pape, Haiti W.P. Parks, USA H.G. Pereira, Brazil P. Piot, Belgium F. Polk, USA J .D. Porter, USA R.W. Price, USA R.J. Riseberg, USA M. Roper, USA A. Rubinstein, USA G. Schochetman, USA N. Schram, USA W.G. Van Acken, The Netherlands P.A. Volberding, USA D. Volkman, USA S. Wain-Hobson, France R. Weiss, UK W. Winkelstein, USA F. Wong-Staal, USA D. Zagury, France V.M. Zhdanov, USSR CONFERENCE COMMITTEES Education/Service Group Subcommittee James C. Hill, Chairman, National Institute of Allergy and Infectious Diseases, National Institutes of Health Stephen Beck, National Association of People with AIDS Terry Beirn, American Foundation for AIDS Research Bernard Branson, HERO James Graham, Whitman-Walker Clinic, Inc. Paul Kawata, National AIDS Network Jeffrey Levi, National Gay and Lesbian Task Force Ann McFarren, AIDS Action Council Carol Sussman, American Red Cross Neil Schram, Los Angeles City/County AIDS Task Force Planning Committee for News Operations R. Anne Thomas, Chairman, National Institutes of Health Winifred Austermann, Alcohol, Drug Abuse, and Mental Health Administration Don Berreth, Centers for Disease Control Geraldine Blumberg, National Institutes of Health James A. Bryant, National Institutes of Health Mary M. Evert, Public Health Service Jack W. Martin, Food and Drug Administration Don Ralbovsky, National Institutes of Health Marc Stern, National Institutes of Health Conference Management Conference Secretariat Melissa M. Widerkehr Nancy E. Shapiro Courtesy Associates, Inc. Fogarty International Center 655 Fifteenth Street, NW. Building 38A, Room B2N13 Suite 300 National Institutes of Health Washington, DC 20005 Bethesda, MD 20892 Phone: (202) 347-5900 Phone: (301) 496-2517 The 111 International Conference on AIDS wishes to express its appreciation to the Agency for International Development for their important support of the Conference . . . and a special thank you to: Abbott Diagnostics Division, Abbott Laboratories for their contribution to Wednesday’s Reception/Buffet. Bio-Data Corporation, publishers of the AIDS Record, for their contribution to the poster session. Burroughs Wellcome Company for their contribution to the Abstracts Volume. E.R. Squibb & Sons, Inc. for their contribution to the Abstracts Volume. Genentech, Inc. for a general contribution to the Conference. Johnson & Johnson Biotechnology Center, Inc. for a general contribution to the Conference. Merck Sharp & Dohme Research Laboratories for a general contribution to the Conference. Merrill Dow Pharmaceuticals, Inc. for their support of the Stone House Committee Event. Organon Teknika for their contribution to the Final Program. The Upjohn Company for their contribution to foreign travel. TABLE OF CONTENTS ' 3333333333333: HHHHHOOOQOKMAwNH Ari—to HOOOQQMAWNr—t fififigfifififiég O 2 v-c 595: Opening Plenary Session ........................................................................................... 1 Plenary Session I .................................................................................................... 1 Epidemiology—Natural History .................................................................................. 1 Virology—Structure and Function I .............................................................................. 2 Psychosocial—Behavioral Studies of AIDS ..................................................................... 3 Prevention/Public Health—Impact of HIV Testing on the Behavior of Homosexual Males .............. 4 Roundtable Discussion—Communicating AIDS Education Across Cultural Barriers .................... 5 Epidemiology—AIDS in Developing Countries ................................................................ 5 Virology—Structure and Function 11 ............................................................................. 6 Immunology—Viral Proteins and Virus Specific Immune Responses ....................................... 7 Clinical Management—Cancer, Hemophilia and Cardiovascular Disease ................................... 8 Roundtable Discussion—Prevention and Control of AIDS in Developing Countries ..................... 9 Roundtable Discussion—The Status of Screening: Supplementary Tests for HIV Infections ............. 10 Roundtable Discussion—AIDS and the Media ................................................................. 10 Monday Poster Session ............................................................................................. 10 Plenary Session II ................................................................................................... 52 Plenary Session III .................................................................................................. 52 Epidemiology—Serology ........................................................................................... 53 Virology—~Antivirals ............................................................................................... 54 Clinical Management—Neurology ................................................................................ 55 Prevention/Public Health—Reaching the General Public ...................................................... 56 Epidemiology—Surveillance: Incidence, Prevalence and Trends ............................................. 57 Clinical Trials—AZT and Ribavirin .............................................................................. 58 Immunology—HIV-Specific Cytotoxicity ........................................................................ 59 Psychosocial—Psychosocial Research: At Risk Populations .................................................. 60 Roundtable Discussion—Access Issues Associated with AIDS: Discrimination, Services, Care ........ 61 Roundtable Discussion—Use of AZT in HIV Infections ...................................................... 61 Roundtable Discussion—Encouraging Physician Counseling for AIDS Prevention ....................... 61 Roundtable Discussion—Legal, Ethical and Public Policy Issues: International Perspective ............. 61 Roundtable Discussion—Psychological Distress and Maintenance of Behavior Change in HIV Illness ................................................................................................................. 61 Biology of HIV ...................................................................................................... 61 Tuesday Poster Session ............................................................................................. 62 Plenary Session IV .................................................................................................. 105 Epidemiology—Heterosexual Transmission ..................................................................... 105 Virology—Vaccines ................................................................................................. 106 Blood and Blood Products—Screening and Donor Characteristics .......................................... 107 Clinical Management—Pulmonary, Pediatric and Neurologic Implications ................................. 108 Roundtable Discussion—Hetrosexual Transmission of the AIDS Virus .................................... 109 Roundtable Discussion—Vaccine Related Issues ............................................................... 109 Roundtable Discussion—Legal, Ethical and Public Policy Issues: The American Perspective ........... 110 Roundtable Discussion—Assuring an Adequate Blood Supply of Healthy Blood Donors ............... 110 Roundtable Discussion—Meeting Gaps in Medical Needs .................................................... 110 Wednesday Poster Session ......................................................................................... 110 Plenary Session V ................................................................................................... 153 Virology—Related Viruses ........................................................................................ 153 Health Care—Patient Care, Attitudes, Knowledge, and Risks ............................................... 154 Clinical Studies—Opportunistic Infections ...................................................................... 155 TABLE OF CONTENTS Th. 5 Prevention/Public Health—Drug Users and Other High Risk Groups ...................................... 156 Th. 6 Roundtable Discussion—Developing Community- -Based Service Organizations ........................... 157 Th. 7 Epidemiology—Perinatal Transmission and AIDS ............................................................. 157 Th. 8 Clinical Management—Infections I ............................................................................... 158 Th. 9 Immunology—HIV Specific Antibodies ......................................................................... 159 Th.10 Blood and Blood Products—Transfusion Associated AIDS and Hemophilia .............................. 160 Th.11 Health Care—Issues in Health Care Delivery .................................................................. 161 Th.12 Roundtable Discussion—People Living With AIDS: Personal Perspectives ................................ 162 Th.13 Roundtable Discussion—Prevention of Perinatal Transmission of HIV Infection .......................... 162 Th.14 Roundtable Discussion—AIDS Education for the General Public ........................................... 163 Th.15 Roundtable Discussion—AIDS in the Developing World (Social/Economic) .............................. 163 Th.16 Roundtable Discussion—Hemophilia: Where Should the Preventive Effort Be Placed? .................. 163 Th.17 Roundtable Discussion—Current Issues in Drug Abuse and AIDS ......................................... 163 THP Thursday Poster Session ............................................................................................ 163 F1 Epidemiology—HIV-AIDS Cofactors ............................................................................ 206 F2 Virology—Diagnostics ............................................................................................. 207 F3 Clinical Management—Infections II .............................................................................. 208 R4 Immunology—Immunopathogenesis ............................................................................. 209 F5 Legal/Ethics .......................................................................................................... 210 F6 Epidemiology—Other Retroviruses .............................................................................. 211 F7 Virology—Animal Models ......................................................................................... 212 F8 Prevention/Public Health—Monitoring Changes in Sexual Behavior ........................................ 213 F. 9 Immunology—Viral Replication .................................................................................. 214 F. 10 Closing Plenary Session ............................................................................................ 215 Authors Index ............................................................................................................... 217 MONDAY, JUNE 1 Opening Plenary Session M.1 General Introductory, Welcoming and Keynote Remarks Speakers include: The Honorable George Bush, Vice President of the United States Robert E. Windom, Assistant Secretary for Health, U.S. Department of Health and Human Services, Washington, D.C. C. Everett Koop, Surgeon General and Director of the International Health Program Office, U.S. Public Health Service, Washington, D.C. Lowell T. Harmison, Deputy Assistant Secretary for Health, U.S. Department of Health and Human Services, Washington, D.C. Carlyle Guerra de Macedo, Director, Pan American Health Organization, Washington, D.C. George J. Galasso, General Chairman, III International Conference on AIDS and Associate Director for Extramural Affairs, National Institutes of Health, Bethesda, Maryland. Plenary Session I M-2-1 The AIDS Viruses Robert Gallo, National Cancer Institute, National Institutes of Health, Washington, D.C. ABSTRACT NOT AVAILABLE AT TIME OF PRINTING nfl.2.2 .Significance of variation between human immunodeficiency (HIV) isolates for serology 2nd vaccine development. ERLING NORRBY* GUNNEL BIBERFEL , JAN ALBERT* ***, FRANCESCA CHIODI*, KRISTINA LJUNGGREN*,****, EVA-MARIA FENYU*, *Dept. Viro ogy, Karo inska Institute, **Uept. Immuno ogy and *** Dept. Virology, National Bacteriological Laboratory, and ****Dept. Inmunology, Karolinska Institute, Stockholm, Sweden. Two groups of HIVs have been identified. The group of HIVs isolated from West Africans includes the strains HTLV-4, LAV-Z and SBL-6669. These strains have closely related envelope glycoproteins, which differ markedly from the corresponding proteins of HIVs represented by the strain HTLVIIIB. This difference is reflected in distinctive reactions in antibody—dependent cell cytotoxicity of antibodies against HIV and the HIV-related West African virus isolates. The internal components of HIVs of both groups share immunogenic properties, but certain distinguishing features have been identified. The occurrence of the two groups of HIVs need to be considered in development of accurate and sensitive serological tests and in attempts to introduce effective immunoprophylactic measures. Site—directed serology using synthetic peptides offers attractive possibilities for establishment of serological tests which can distinguish antibody responses to viruses representing the two groups of HIVs. In_2_3 The natural history and clinical manifestations of HIV—infection PETER PIOT. Institute of Tropical Medicine, Antwerp, Belgium. The clinical expression of HIV—infection appears increasingly complexe. It includes manifestations due to opportunistic diseases, as well as illness directly caused by HIV itself. Neurological disease may include involvement of brain, spinal cord and peripheral nerves, and is probably directly caused by HIV, as is lymphocytic interstitial pneumonia. The etiology of chronic diarrhea and a popular pruritic skin eruption associated with HIV—infection is unclear. Several clinical classification systems for HIV—infection have ben proposed. Between 2 and 8 Z of infected individuals per year progress to AIDS, with no apparent decrease in the rate of disease progression over time. Within 5 to 10 years of infection the majority of infected persons develop clinical disease. Reported risk factors and/or predictors of di— sease progression such as a decreased number of T—helper lymphocytes, an in— creased number of T—suppressor lymphocytes, a low level of HIV—antibody and a high titer of CMV-antibody, may be markers or reflect duration of infec- tion. A chronically activated state secondary to chronic viral and parasi- tic antigenic exposure may increase both the susceptibility to HIV—infection and development of disease. Increased HIV gene expression and persistent antigenemia may also be contributing factors in disease development. Per— sistent viral production in monocyte/macrophage cells in the brain and elsewhere may be a source of virus production in other organs. Infection of the brain implies that HIV may be protected from immune surveillance or therapeutic intervention. Epidemiology—Natural History In_3_1 The Natural History of Human Immunodeficiency Virus Infection in a Cohort of Homosexual and Bisexual Men: a 7-year Prospective Study. NANCY A. HESSOL*, GN RUTHERFORD*, PM 0'MALLEY*, LS DOLL**, NW DARROW**, Hw JAFFE**, gg gl., *Dept.of Public Health, San Francisco, CA, and Centers for Disease Control, Atlanta, GA. _ To determine the natural history of HIV infection, a stratified random sample of 6,700 homosexual and bisexual men originally recruited between 1978 and 1980 for studies of hepatitis B were evaluated. To date, 662 (9.9%) of these men have been reported with AIDS, and approximately 70% are estimated to be infect- ed with HIV. Of the 719 (11%) men randomly chosen from the entire cohort who participated in AIDS studies, 63 were known to have seroconverted before the studies began in late 1983. These 63 men have now been followed for a mean of 72 months since their initial seropositive specimen or estimated date of sero- conversion: 19 (30%) have been reported to have AIDS; 29 (46%) had generalized lymphadenopathy, oral candidiasis. weight loss, persistent idiopathic fever or diarrhea; and 15 (24%) were asymptomatic. Additional data were analyzed from 273 men who participated in hepatitis B vaccine trials, for whom multiple serum specimens were available. and who consented to have their old serum specimens tested for the presence of HIV antibodies. Of these 273 men. 112 (41%) were either seropositive on entry into the cohort (18 men) or had known seroconver- sion dates within a 24 month period (94 men). Combining these 112 men with the 63 men from the random sample, a Kaplan-Meier survival curve of the cumulative proportion of men without AIDS by duration of HIV infection was constructed. From analysis of these 155 men, an estimated 15% (95% confidence interval, 9 - 21%) of the HIV infected men in the Clinic cohort will develop AIDS over 60 months of infection, 24% (95% c.i., 17 - 31%) will develop AIDS after 72 months, 31% (95% c.i., 22 — 40%) will develop AIDS after 84 months, and 36% (95% c.i., 26 - 46%) after 88 months. “0.3.2 In a Cohort of HIV Seropositive Men Followed for 30 Months, Initial Ieu 3a T lymphocyte Counts Predict Subsequent Declines in T Cell Counts, Clinical Findings and AIDS WILLIAM IAbE*, R. ANDERSQV**, W. WINKEISTEIN, Jr.***, R. ROYCE***, H. PERKINS****, *Children's Hospital of San Francisco, CA, **California Departnent of Health Services, Sacramento, CA, ***UCB School of Public Health, Berkeley, CA, ****Irwin bknorial Blood Bank, San Francisco, CA. Fran the San Francisco Men's Health Study, a prospective study of HIV infec— tion in a population-based probability sample, 370 HIV-infected nan were recruited. A subset of 206 men attended examinations every 6 nrmths fron June 1984 through December 1986. Initial Ieu 3a ccunts were unincdally distributed and depressed ccnmaxed to uninfected men. CNer 30 months, the entire distribution shifted toward lower values. when the group was strati- fied according to initial Leu 3a ccunt, declines of 18 to 30% occurred in all quartiles indicating depletion of Ieu 3a cells regardless of initial values. To explore the relationship of initial Leu 3a values to developnent of HIV related synrdzns and AIDS, all 370 seropositive men were stratified into groups with less than 500 (n=100), 500—650 (n=92), 650-800 (n=81), and greater than 800 (n=97) initial Leu 3a cells. Ancmg participants with less than 2 symptons suggestive of HIV infecticn at outset, 25% with less than 500 Ieu 3a cells developed increasing sympbuns cxnmared to 12% of those with greater than 800 Ieu 3a cells. Twenty-four of the 37 AIDS cases occurred in the lowest group ccmpared to 5 in the highest. These findings suggest that HIV infection affects Leu 3a ccunts progres- sively in most people and that initial Leu 3a number is strongly predictive of clinical outcane in the ensuing 30 nrmths. MONDAY, JUNE 1 M 3.3 Progression to AIDS, predictors of AIDS, and seroconversion in a cohort of homosexual men: Results of a four year prospective study. MARTIE I $§HEQHZFEK W] BOYKO, MS WEAVER, B DOUGLAS, B WILLOUGHBY, WA MCLEOD, et al. The Vancouver Lymphadenopathy-AIDS Study, St. Paul's Hospital, University of British Columbia, Vancouver, BC, Canada. The Vancouver Lymphadenopathy-AIDS Study is an ongoing prospective study of over 600 homosexual men who were recniited through their CP‘s beginning in 11/ 82 and who have been seen since at roughly six-month intervals. A total of 323 men were seropositive at entry into the study. Through 11/ 86, a total of 36 cases of AIDS were diagnosed in this group, yielding a Kaplan-Meier (K-M) estimate for the 48 month cumulative incidence of AIDS of 18.6%. The following are the categories (and K-M estimates of the four-year incidence of AIDS) for the lab predictors of progression to AIDS: CD4 count <4IX) (33.6%) CD4/CD8 ratio <.75 (36.9%) lgG >16m(260%) >400 (14.3%) p=.0m1 >75 (11.1%) p=.0001 <16m (142%) p=.(I13 IgA >750 (373%) C1qbinding >8% (305%) I-Ibg <15.0 (28.4%) <250 (93%) p=003 <8% (6.1%) p=.034 >15.0 (72%) p=029 Cox regression revealed that CD4 cell depletion, lgG elevation, and IgA elevation, were significant and independent predictors of progression to AIDS in seropositive homosexual men. Of 345 men who were HIV negative at enrolment, 85 (25%) have seroconverted by the time of this analysis. The K-M estimate for the risk of seroconverting during 11/ 8207/ 86 was 22.5%. The seroconversion rates during 5 successive 9 month periods from 11/82 to 07/86 were 4.4%, 9.1%, 5.2%, 4.3%, and 1.7%. Cox regression analysis revealed the following significant risk factors for seroconversion: number of sexual partners, receptive anal intercourse, history of gonorrhea, use of illicit drugs, and age below 30 in ”/82. That men under 30 were twice as likely to seroconvert as older men appears to be due to lesser modification of behavior in the younger group. In fact, the proportions of men in the age groups <30, 30-34, 35-39, and 40+, reporting a decrease in the annual number of sexual partners were 49%, 56%, 61%, and 68% respectively. Additional counselling about safer sexual practices should therefore be selectively directed to younger members of the gay population. “a 3 4 Natural Histor of HIV Infection in Intravenous Dru Abusers (IVDAs) ' ' PETER A SELWYN , EE SCHOENBAUM*, D HARTEL*, T PETE **, RS KLEIN*, GH FRIEDLAND*, et al, *Montefiore Medical Center/Albert Einstein College of Medicine, Bronx, NY, **CDC, Atlanta, GA, USA. We are prospectively studying patients in s methadone maintenance program in NYC to characterize the natural history of HIV infection in this group ofIVDAs. From 7/85—4/86, 498 patients enrolled in an HIV seroprevalence study; we now present preliminary follow-up data. All subjects had an initial interview regard- ing drug use and sexual behavior, serum was obtained for HIV antibody (Ab) ands physicial exam was performed. Rescreening visits are scheduled semi-annually, with interview, repeat Ab tesn and exam. All patients receive on-site primary care and are monitored by clinical staff for the occurrence of AIDS/HIV disease. In the original group, there were 169 seropositives (SP) withoutAIDS,and 329 seronegatives (SN). 91 (54%) SP5 were male; mean age was 33 yrs.; 17 (102) were white (W), 54 (322) black (B), 98 (58%) Hispanic (H). 5 of 6 SPs with oral thrush (0T) at study entry developed AIDS at a mean of 4.7 mos. follow-up. 163 SPs with- out OT have been followed for a median of 15 months (range 10-20). of these, 6 (3.7%) developed AIDS and 2(1.2.Z) presumptive AIDS at a mean of 12.3 mos.fol— low—up. Among SPs without 0T, cumulative incidence of AIDS was thus ~51, with 2.7 cases/1000 person-monthsfollow—up. 0f 13 cases of AIDS/presumptive AIDS, 8 (622) were male; mean age 34 yrs.; 1 was W (82), 6 B (462), 6 H (462).Multip1e logistic regression analysis including demographic, drug use, and sexual varia- bles from initial interview data indicated that black race (p(.01),prostitution (p(.02), and drug use in a "shooting gallery" (p(.03) were all predictive ofthe development of AIDS among SPs. 44/169 (262) original SPs have been formally re- screened to date. 5/44 (112) had new generalized lymphadenopathy on exam and 2/44 (51) had new 0T at a median of 14 mos. follow-up. Results indicate that HIV-infected IVDAs progress to clinical disease at a substantial rate; AIDS was predicted by certain drug use and sexual behaviors. The observed association with race requires further explanation. In_3_5 Risk of Disease in Recipients of Blood from Donors Later Found Infected with Human Immunodeficiency Virus (HIV) J.w. wanna D. DEPPE*, H. PERKINS", s. KLEINMAN***, r HOLLAND", J Allen", *Centers For Disease Control, Atlanta, Ga,** Irwin Memorial Blood Bank, San Francisco,*** American Red Cross, Los Angeles, + Sacramento Blood Center, Sacramento CA. Recipients of blood from donors later found infected with HIV are unique in that their date of infection is known, and the natural history of HIV infection may be more easily observed. We have identified 777 recipients of blood from 131 donors later found to be infected with HIV. of 457 recipients investigated, 155 (341) survived less than 4 months post-transfusion, 249 (541) survived longer than 4 months, and 53 (122) were lost to follow—up. of those who survived longer than 4 months, 18 (71) developed AIDS 10 to 63 months after transfusion (median 28 months). of the 54 HIV-seropositlve recipients followed an average of 46 months after transfusion, 28 (521) have remained asymptomatic, 12 (221) have generalized lymphadenopathy, 9 (171) have AIDS-related complex, and 5 (9%) have developed AIDS. of these 54 recipients, 13 (241) had an acute illness compatible with acute retroviral syndrome. 0f 19 tested asymptomatic seropositive recipients, I4 (742) had low T-cell helper:auppressor ratios. The 49 seropositive recipients without AIDS were not significantly different than the 18 who developed AIDS by sex (472 male vs 391 male), age at transfusion (49 years vs 52 years), and total blood received (7 units vs 16 units). However, the 18 AIDS patients more frequently had blood and clotting disorders (usually autoimmune) than did the other seropositive recipients (281 vs OX, p(0.001). Blood recipients from infected donors are at high risk for HIV—related disease. The association of blood and clotting disorders with the development of AIDS is under investigation. M'3_6 Continuing Studies on the Natural History of HIV Infection in Zaire. BOSENGE WALY", R.W. RYDER", B. KAPITA“, H. FRANCIS"*, T. QIINN'", J.M. MANN** er a1., “Mama Yemo Hospital and Department of Public Health, Kinshasa, Zaire, *3CDC, Atlanta, 3'3 NIH, Bethesda. In November, 1986 2020 hospital staff members at Mama Yano Hospital were re-examined for HIV antibodies. Among the 44 employees who were asymptom- atically HIV-infected in 1984 and who were followed up in 1986, 2 had developed AIDS (2.3 cases/person years of observation [PYO]). During the 2-year period, an additional 18 of these 44 patients but only 1 of the 1958 persistently HIV(-) tients developed signs/symptoms consistent with AIDS- related complex [ARCfia (ARC rate of 20.4 cases/100 PYO in seropositives, .05 rate in seronegatives). Nine of 18 HIV(+) symptomar ic patients in 1984 had a marked decline in clinical status when re-seen in 1986. Ten (7.1%) of the 140 1984 HIV(+) employees on whom information could be obtained. in 1986 had died. There were 41 seroconversions during this period for an infection rate of 1.0/100 PYO. Fifty-eight percent of the new infections were in men. average age of patients with new infections was 41.4 years for males and 35.5 years for females. Nenty four percent of new female infections had had a spontaneous abortion compared with 4% of previously infected and 11 of non-infected women. Nine new‘infections had ARC at the time they were examined. New infections did not cluster in employee groups having the most contact with patients or their body fluids. In this representative urban, middle-class, African population with 1% yearly HIV incidence, an important rate of disease progression has been documented. Virology—Structure and Function I Pathogenesis of HIV Infection - Virus: Host Interactions nn'4'1 JAY A. LEVY, Department of Medicine and Cancer Research Institute, University of California, School of Medicine, San Francisco, CA, 94143. The human immunodeficiency virus (HIV) is a human lentivirus that has a variety of heterogeneous subtypes. They can be distinguished by replicating properties in different cell types, cytopathology. induction of a latent state, sensitivity to serum neutralization, restriction enzyme patterns, and nucelo— tide sequences, particularly in the envelope region. These properties of HIV contribute to the pathogenicity of some isolates. The immunologic responses of the host determine whether the infection with HIV progresses to disease, or whether the virus is kept under control. Strong cell-mediated immune re- sponses appear responsible for suppression of virus replication and spread. Other immune reactions may advance the state of the disease, such as autoanti- bodies against platelets, helper T lymphocytes and other host cells. The form- ation of immune complexes containing HIV antigens and viral proteins may com- promise immune function. The malignancies in AIDS may result from an enhanced response of certain cells in the immune system. B cell lymphomas may result from lymphokine or antiidiotype production, and Kaposi's sarcoma may represent proliferation of endothelial cells responding to enhanced angiogenesis—promot— ing factors. These malignancies may be linked as well to Epstein-Barr virus, CMV or papova viruses. The pathogenesis of HIV infection, therefore, is the end result of an interplay between particular HIV with specific host responses. An understanding of the factors involved is important in our approaches at control and prevention of HIV infection. M 4 2 Clonal Analysis of Functional Differences of Human ' ' Immunodeficiency Virus (HIV) SHINJI HARADA", N. YAMAMOT0**, Y. HINUMA", Institute for Virus Research, Kyoto University, Kyoto 606, ‘*Dept. of Virology and Parasitology, Yamaguchi University, School of Medicine, Yamaguchi, 755 Japan. Different isolates (HTLV—IIIB, LAV-l, ARV-2) of HIV were cloned by a novel plaque—forming method using a HTLV-I carrying cell line MT—4. All viral preparations were titrated by reverse transcrip- tase (RT) activity and plaque-forming unit (PFU). PFU/RT values which indicate the relative proportion of incomplete and infec- tious viruses were used for the determination of the viral infec- tivity. High values were obtained mainly from clones of HTLV-IIIB and LAV—l, while low values were from ARV-Z—derived clones, suggesting that ARV-2 and its clones were genetically less infec- tive. To assess cytocidal effect of the viruses, we selected and used 4 clones with similar PFU/RT value (infectivity) for prolife- ration assay of infected MT-4 cells, one (HTLV-IIIB-C~2) of which was found to kill more cells than others even at the same doses (More). Furthermore, plaques induced by the HTLV-IIIB—C—Z-hficoufi cell were larger than others, suggesting that release (prolifera— tion) of the progeny was maximum in HTLV-IIIB-C-Z—infected cell. Among clones tested, three were found to induce strong cytopathic changes (fusion and ballooning ) selectively to MT-4 cells. Thus, we concluded that infectivity, proliferation and cytopathic fusion-effect might be encoded by the viral genome and be separa- ble by the plaque-cloning method. MONDAY, JUNE 1 In 4.3 T4 Glycoprotein and T4 Messenger RNA in Human Immunodeficiency Virus-Permissive cells M. MALKOVSKV, KAREN PHILPOTT*, A. HsLLox‘, P.J. MAbb0N**, R. AXEL***, A.G. DALGLEISH, et al., Retrovirus Research Group and *Transplantation Biology Section, MRC Clinical Research Centre, Hatford Road, Harrow, Middlesex HA1 32% England; Department of Biochemistry and Molecular Biophysics and Howard Hughes Medical Institute, College of Physicians and Surgeons, Columbia University, New York, New York 10032, USA. The mere presence of the T4 molecule on the surface of both human lymphoid and non-lymphoid cells is sufficient to render the cells susceptible to human immunodeficiency virus (HIV) infection in vitro (Maddon et al., Cell 41, 333-348, 1986). Recently, we have identified a B-lymphoblastoid cell line (Gupta) which expresses neither T4 on the cell surface (FACS analysis) nor T4 mRNA (Northern blotting, SI nuclease protection assay). However, Gupta cells can be productively infected with HIV using a relatively low dose (10 infectious units per m1) of virus. Interestingly, the HIV infection of Gupta cells is not associated with syncytial formation, which is typically induced by HIV in T4-positive cell lines. Also, the CD4 monoclonal antibodies (anti-Leu-Ba and DAKO-T4), which block the cytopathic effect of HIV on T lymphocytes do not inhibit the HIV infection of Gupta cells. Finally, we have studied several monkey species and found that T lymphocytes of the olive baboon (Papio anubis) and the common marmoset (Callithrix jacchus) express certain epitopes pertinent to HIV infection, suggesting that these species could serve as a model of HIV infection in viva. RE 4 4 Delineation of a Region of the HIV gPlZO Envelope Protein which ' ' Interacts with the CD4 Antigen of the Helper T Lymphocyte LAURENCE A. LASKV, T. GREGORY, G. NAKAMURA, C. FENNIE, D. SMITH, P. BERMAN, et a ., Departments of Molecular Biology, Process Development, and Assay USvETopment, Genentech, Inc., 50. San Francisco, CA, USA. The most important initial event in the infection of cells by HIV is the interaction between the virus envelope protein, gPlZO, and its cellular receptor, the CD4 antigen. In order to understand this interaction, we have begun to investigate the regions of the envelope antigen which interact with the CD4 protein. Previously, we demonstrated that large quantities of a secreted form of the HIV gPl20 antigen could be produced in permanent mammalian cell lines. A radiolabelled form of this envelope protein has been found to bind to a recombinant CD4 antigen with high affinity, and this binding can be inhibited by the appropriate 0KT4 monoclonal antibodies as well as human neutralizing sera. A number of monoclonal antibodies specific for gPlZO have been tested for their ability to block this interaction, and one has been found to be effective. The gPlZO epitope which interacts with this blocking monoclonal antibody has been isolated by passing a mild acid hydrolysate of gPlZO over an immunoaffinity column which utilized the blocking monoclonal antibody. One peptide specifically bound to the column, and N-terminal sequencing revealed that it was located in the C-terminal portion of the envelope protein. In order to further analyze this region, 13 vitro mutagenesis of the HIV envelope gene was used to delete a small region of the envelope protein within the peptide which bound to the blocking monoclonal antibody. The resultant mutant gPlZO protein was unable to bind to the CD4 antigen. hfl.4.5 Reversion of a Non-infectious Envelope Mutant of the Human Immunodeficiency Virus in a Tissue Culture 5 stem. RONALD L. WILLEY', DANIEL J. CAPON**, THEODORE THEODORE , MALCOLM A. MARTIN“. Laboratory of Molecular Microbiology, NIAID, NIH, Bethesda, MD 20892; and MGenentech, Inc., South San Francisco, CA. Site specific mutagenesis has been used to introduce a single amino acid substitution within the £21 gene of the human immunodeficiency virus (HIV). The substitution of a glutamine for an asparagine codon at a potential N-linked glycosylation site within a highly conserved region of EEK gp120 resulted in the production of defective virions. Particles produced following transfection of the mutant clone into a colon carcinoma cell line were unable to infect T4+ lymphocytes. However, revertant infectious particles appeared in long-term cocultures of transfected colon cells and T4+ lymphocytes. In three of nine experiments, infectious virions were detected at 26, 35, and 35 days after the addition of lymphocytes. Revertant proviral DNAs were cloned and their en: genes sequenced. These results indicate that the HIV genome can undergo variation during replication in tissue culture in the absence of any immune pressure. ln_4_6 Structure/Function Relationships of the HIV Envelope Glycoproteins MARK KOWALSKI, JOSEPH POTZ, WEI CHUN GOH, LADAN BASIRIPOUR, CRAIG ROSEN, ANDREW DAYTON, ERNEST TERWILLIGER, WILLIAM HASELTINE*. JOSEPH SODROSKI Dana-Farber Cancer Institute, Dept. of Biochemical Pharmacology:_HE?VE?a_MEH: ical School, and *Dept. of Cancer Biology, Harvard School of Public Health, Boston, MASS. The HIV envelope glycoproteins play a central role in virus entry into the host cell and in the direct cytopathic effect of HIV infection on T4 bearing cells. Plasmids expressing mutant HIV envelope proteins were constructed and used to transfect human T and B lymphocyte lines. Expression and processing of the HIV envelope was monitored as well as the ability of the mutant envelope protein to bind to the T4 receptor and to induce the formation of syncytia by membrane fusion. Mutations affecting the association of the gp120 exterior protein and the gp41 transmembrane protein, mutations affecting the binding of the gp120 to the TA molecule, and mutations affecting post-TA—binding steps in the process of syncytium formation were defined. The ability of anti-peptide sera or sets from HIV infected individuals to interfere with the function of envelope proteins derived from divergent HIV strains was examined. Psychosocial—Behavioral Studies of AIDS “A‘s 1 Neuropeptides and the HIV receptor: Peptide T _ and its Pentapeptide Analogues are Potent CD4 Receptog Eigands Present in env of All HIV Isolates. MR RUFF, J HILL, C SMITH, P HALLBERG, E STERNBERG, N JELESOFF,JB O'NEILL, CB PERT Brain Biochemistry, CNB, NIMH, Bethesda, MD 203§2 USA We have previously reported on the deduction of peptide T as the putative attachment sequence by which HIV binds to macro- ages, T cells, and brain cells (Pert et al PNAS 83,'86). We have obtained E H -D-Ala -peptide T and developed specific receptor binding assays to the 60 kD T mdlecule present on rat, human, and monkey brain membranes as well as humafi T cells and mouse macrophages. The core sequence necessary for CD receptor activity is the pentapeptide TTNVT whose analogues appear in all HIV isolates obtained to date as well as HTLV I and II. Pentapeptides have been synthesized and demonstrated to have potent bioactivity in human monocyte chemotaxis (Ruff et al FEBS 211), and in displacement of f H] peptide T from human T cells, rat hippocampal membranes, and mouse macrophage membranes. T4 receptor binding can be detected only on T positive clones, but not on T4 negative clones. D—amino acid Tyr substitugion in the critical, highly conserved 4 position results in a virtual total loss of bioactivity. Requirements for tertiary structure for bioactivity will be described. The origanal anté-viral demonstration has been extended to A3.01 cells in which 10 to 10 M peptide T and its pentapeptide analogs reduce infectivity of the entire course of infection by 80-90%. VIP, a neuropeptide enriched in cortex and sacral autonomic ganglia, shares structural homology since VIP7—11 is TDNYT and this neuropeptide is active at C0,. We hypothesize that the VIP-mimetic properties of HIV env produce the profound immunological failure and psychotomimetic disorders chracteristic of AIDS. “H's-2 Carl Eisdorfer, University of Miami, Miami, Florida. ABSTRACT NOT AVAILABLE AT TIME OF PRINTING MONDAY, JUNE 1 In 5.3 PSYCHOIMMUNOLOGIC RESEARCH AND AIDS T. Peter Bridgel M.D., Intramural Research Program, National Institute of Mental Health, Bethesda, Maryland 20892 The neurotrophic nature of HIV infection has led to\numerous clinical descriptions of CNS correlates of AIDS, ARC, and HIV infection. These include cognitive, motor, and behavioral change believed secondary to HIV infection itself rather than to the opportunistic CNS infections consequent to the profound immunologic dysregulation of AIDS. AIDS treatments are proposed or being tested that are known to be associated with demonstrable neuropsychiatric sequelae. Not only the neurotrophic nature of HIV, but also the increasing documentation of the interdigitation of the immune, endocrine, and central nervous systems predict that an immunologic infection by HIV would have CNS consequences and that effective treatments will either be active in the CNS and/or have side effects in the CNS. Data will be reviewed addressing the biobehavioral basis for AIDS research arising from the integration of the immune and central nervous systems. Evidence for the identity of neurotransmitters and immunotransmitters will be presented as well as emerging research on the impact of behavior on immuno/neurotransmitters and the behavioral sequelae of immuno/ neurotransmitter modulation. This paper serves both to provide background for the other papers presented in this session as well as to discuss a future direction of AIDS research in the near tenm M.5.4 An unspeakable Disease.Self—Isolation of HIV infected pa: tients as a result of Conflicting Aspirations ' 3C.GHARAKHANIANTW.ROZENBAUM?A.VIALLEFONT§F.AIME;" GSPM,CNRS,Paris/‘Fac.de Médecine,Univ.Paris;"U-194,INSERM,Paris, France 104 patients (38 AIDS,14 ARC, 43 Lymphaden.,9 Asympt.)of a Paris hospital were interviewed in March and April 1986 about changes in their social and work relationships, psychological stress and their speaking about the diagnosis. Most patients including married men and gays living in couple relationships speak only with the closest persons, 50% of L and A aid 30% of ARC and AIDS with nobody about their illness. Except for a drastic decline in sexual activities, nothing apparently changes in their personal life and work before longer periods of hospitalisation. Although suffering from insomnia, depression and anxieties, only 6% of patients sollicit or accept psychological and psychiatric help, less than 10% support services offered by associations. Patients tend to refuse help because con= tinuing a "normal life" symbolizes hope. But this is only possible by hiding ones diagnosis.This attitude then hinders mobilizing sup= port around them.This suggests that patients live with contradicto= ry aspirations that compare to a double bind situation as seeking help and breaking the silence is easily identified with giving up one's hope and abandoning one'self in a situation overdetermined by the threat of death. Only wide social acceptance of HIV infection as a can help to solve this psychological dilemma. M 5' 5 An Intensive Psychoimmunologic Study of Long— Surviving Persons with AIDS ,J zxcu, or. SOLOMON, D..P STITES, UCsF School Med., CA. Given the increasing number of studies which link stress and/or behavioral factors with immune response and disease progression, psychosocial factors might be expected to play a role in AIDS. While there has been much interest and speculation about the relationship of psychologic and immunologic factors in AIDS, there are no completed studies in this area, to date. The present study is con- cerned with the interactions among psychosocial, immunologic, and psychophysio- logic parameters in persons with AIDS who have varying durations of survival. Initially, 5 subjects were diagnosed with AIDS for less than one year (i: 8 months), 8 were diagnosed between 1 and 2 years Iago (r: 19.9 months), and 5 "long-surviving" men were diagnosed more than 3 years ago (Y: 42.4 months). Blood was drawn prior to an initial psychosocial interview and 6 weekly interviews addressing recent emotional experiences and related coping patterns. Blood was assayed for helper-inducer and suppressor—cytotoxic T cell numbers and ratio, Natural Killer cell numbers and function, virus "specific" T cells, large granular lymphocytes, activated suppressor cells, activated helper cells, B cells, and cortisol levels. The six emotion-related interviews were videotaped and subjects were monitored—for heart rate, skin temperature, skin conductance, and respiration. Various psychosocial measures were administered to assess social support, stress, daily moods, health-promoting activities, and psychological "hardiness." Relationships among immunologic and cortisol levels, psychophysiological reactivity, emotional expressiveness, and stress/coping indices will be presented. The data analyses focus on within subject patterns of co-variation, as well as differences across subjects, particularly, patterns that distinguish "long-surviving" persons with AIDS. Further analyses will investigate factors related to actual duration of survival from time of diagnosis. "normal disease" Vlrll Ilpldo u I all. 01 acllon lor devoloplna novel antI-vlral open“: Sludles wIIII AL721 A. s LIppa‘ F T Crews2 M H. orieoo3. E Bulrnovlcl- Klelna. M. Lanoea. D. I. Scheer‘. andc. A. Klepner‘; 1Praxls Pharmacsullcals Inc Beverly Hills. 6A.. 2Unlverslly 0! Florida MsdIcaI School Gainesvllle FLA. 35L Luke‘s/Roosevell HospIIaI Center New York. NY. Vale University School oI Medicine. New Haven. OT A major underlying lhsme In biology Is lhe underslanding that many lmponanl processes Involve the recognition oI biologically relevant substances by spacllic receptor molecules This theme can be observed In such diverse as 1)Ihe L ol ’ lo their ,,,. ,. lam receplor proteins. 2) Ihe binding oI anligens lo anllbodies and 3) Ihe Inleclion oI host cells by vimses In lhese cases. successlul receptor blndlng ls hlghly dependenl on me orienlalion and tertiary conlcrmalion ol the Interacting molecules. which in [he case oI membrane prolelns ls regulated by the lipid r ilion ol the Human ImmI y vas (HIV). an enveloped retrovirus. attaches to T4 Iymphocyle receplovs with high speclliclly. Based on Ihe high llpld oomposllion (approx. 50%) 0I HIV. hs hypervisoous nature and abnormally high (21) cholesterol to phospholipid molar ratio (C/P). we believe lhal the viral envelope may have an lmponanl role In malnlaining lhe slruclural inlegrily and lnleclivily ol the virus by providing a rigid lipid matrix enabling lhe viral attachment prolelns to maimain the proper conlonnalionlorlenlallon Ior binding lo T4 receptors. AL721 is a unique mixture oI orally active lipids which has been shown previously lo modify membrane lipid composition and to enhance lipid bilayer membrane fluidity by the extraction ol cholesterol lrorn cell membranes with high C/P. Trealmenl wiIh AL721 decreased the cholesterol content and altered the biophysical properties of HIV envelope in parallel with ils abil'ny Io Inhibil lhe lnlecl'rv'ny of HIV. In eight ,. ,, with II ge- " lyrm ‘ r ,and who were seropos'nlve Ior anlibody and virus. eighl weeks treatment wllh AL721 decreased mean blood levels of reverse Iranscriptase aciivily by 60% and Increased the diminished lymphoprolileralive responses Io both pokswsed and calcanvalin A mllogens. These data support the hypothesis that the HIV membrane is a major structural componenl ol the vlrus and that modifications In viral lipld oomposltion by AL721 may prevem viral inleclion cl host cells. M.5.6 Prevention/Public Health—Impact of HIV Testing on the Behavior of Homosexual Males lfl.6.1 Effect of HIVab Serodiagnosis on Homosexual Men in The Netherlands GODFRIED J.P. VAN GRIENSVEN, R.A.P. TIELMAN, J. GOUDSMIT, J. VAN DER NOORDAA, F. DE WOLF, R.A. COUTINHO, et al., AIDS Study Group Amsterdam/Utrecht, P.0. Box 80l40, 3508 TC Utrecht, The Netherlands Between October 1984 and October 1986, 860 homosexual men, living in and around Amsterdam, The Netherlands, were surveyed every six months, regarding sexual behavior. At the start of the study 746 subjects learned their HIVab status, of whom 234 (31 per cent) were HlVab+ . In addition 114 individuals, recruited as controls, were not tested on HIVab. Regarding changes in sexual behavior, data were analysed with analysis of variance in a doubly multivariate repeated measures design. To improve the comparability between groups (obscured by pretest differences in group means and a differential "floor" effect) deviation scores were computed. These express the relative popularity of each sexual technique in relation to all other techniques. Reductions were found in the number of sexual partners and the number of partners on all measured sexual techniques. HIVab tested individuals reported greater reductions than did controls. Cases who were HIVab+ reported the greatest reductions. The relative popularity of masturbation active and passive and anogenital insertive and receptive intercourse remained constant. Ore-oral sexual contact and orcgenital insertive and receptive intercourse became less popular, while oroanal insertive and receptive intercourse became slightly more popular. No substantial differences between groups were found in this respect. Sexual Behavior in “n 6 2 Factors Influencing the Decision to Learn HIV Antibody Results in ' ' Gay and Bisexual Men DAVID W. LYTEH, R.0. VALDISERRI, L.A. KINGSLEY, W.P. AMOROSO, C.R. RINALDO,JR, University of Pittsburgh, Pittsburgh, PA. During the latter part of 1985, 1809 gay or bisexual men enrolled in the Pittsburgh cohort Of MACS (Multicenter AIDS Cohort Study) were invited by mail to learn their HIV antibody results. Participants were asked to complete and return a questionnaire designed to assess the factors influencing their deci— sion about learning results, their recent sexual behavior, their knowledge about AIDS and their attitudes towards AIDS risk reduction. 869 (48%) men ac- cepted the invitation, 160 (9%) declined and 780 (43%) failed to respond.There were no significant differences in demographic, behavioral and attitudinal characteristics or HIV seroprevalence between the men who accepted and those who declined. However, significant demographic differences were noted between the men who responded to the invitation versus those who did not. in that the latter group was comprised of a greater proportion of men who were younger, non—white or less well—educated. The most frequently cited reason (87%) why men wanted their results was to determine if they had been infected with HIV. of those who declined, 31% cited concerns about the psychologic impact of learning about a positive antibody result as being the most important reason for their decision to decline. The most frequently selected contributing rea— son for declining results (61%) was the belief that the test is not predictive of the development of AIDS. 24% believed that the test is inaccurate and 19% expressed concerns about confidentiality. These findings have relevance to the design and implementation of HIV screening programs. MONDAY, JUNE 1 M '6. 3 Sexual practices and condom use in a cohort of homosexual men: Evidence of differential modification between seropositive and seronegative men. BRIAN WILLOUGHBY MT SCHECHTER, WI BOYKO, KIP CRAlB, MS WEAVER, B DOUGLAS, et al. The Vancouver Lymphadenopathy-AIDS Study, St. Paul's Hospital, University of British Columbia, Vancouver, BC, Canada. We have been following a cohort of approximately 600 homosexual men recruited through 6 general practioners with six—monthly questionnaires, physical exams, and lab testing. To assess behavioral change, we compared sexual practices reported at the earliest visit (EV) during the period [03/84 - 12/84] with those reported at the latest visit (LV) during the period [05/85 - 09/86] in all 430 members of our cohort who had complete data for at least 2 visits during the observation period. This included 150 seropositive men with a mean interval between EV and LV of 19.4 months (range=8-28) and 280 serenegative men with a corresponding mean interval of 20.1 months (range=6~29). Overall, the mean annual number of sex partners declined from 7.7 to 6.4 (p<.001). This was confined primarily to the seropositives (9.2 to 5.8; p<.001), as compared to the seronegatives (6.9 to 6.7; p=NS). Because the seropositives had higher levels at EV and thus greater potential to decline, we restricted the analysis to the upper 50% at EV. in this analysis, the seropositives declined from 16.2 to 7.7 (p<.001) while the seronegatives declined from 15.6 to 10.9 (p<.001), with the decline being significantly greater in the seropositives (-8.5 vs 4.7; p=.043). To study condom use in high risk situations, we analyzed their use during receptive anal intercourse with casual partners among those men in the upper 50% of casual sexual contact. At LV, 35% of seronegatives and 7% of seropositives reported never using condoms during this activity (p<.001) while only 42% of seronegatives and 44% of seropositives reported always using condoms during this activity. These data suggest that the very people at continuing risk, namely seronegatives, may have modified their behavior to a lesser degree. Even within an AIDS related study with six monthly visits, less than half of scronegatives reported always using condoms during receptive anal intercourse with casual partners as of their most recent visit. The data suggest that we need to redouble our efforts at educating all people at risk regardless of their HIV status. lfl.6.4 The HIV Antibody Test: Influence on Sexual Behaviour of Homosexual Men. CHARLES F FARTHING”, W JESSON“, HeL TAYLOR", A G LAWRENCE‘, B G GAZZARD*. ”St Stephens Hospital, London, UK. *‘Public Health Laboratory, Collindale Laboratories, London, UK. There has been debate as to whether patients at risk of HIV infection should be execuraged to have an HIV antibody test performed. We therefore conducted a survey bv anonymous questionnaire which was completed whether or not the test was eventually carried out. All patients were counselled prior to being offered the test and a similar questionnaire was completed 3 months after the initial interview. of 324 homosexual men offered the test 87% agreed to be tested although 157 had come to the clinic without this intention. Only 4 patients did not wish to know the results. Sixty five per cent of patients had already modified their sexual behaviour but 93% thought they would be more likely to adhere to safer sexual practices if shown to be positive mheras 79% would do so if the test was negative. Three months later 16% of patients regretted having the test — all had had a positive result. Half of the 83% of patients practicing safer sex felt they were doing so as a result of the counselling, but the rest as a result of the test being positive. Our results suggest that the maiority of gay men (88%) wish to know their HIV antibody status and that having the test performed encourages the adoption of safer sex practices. M 6 5 Evaluation of Anti-HIV Testings in Sweden, 3 Country where HIV In- ' ' fecticns are Subjected to Legislation Professor M. BfiTTIGER M.D., Nat. Baet. Laboratory, Stockholm, Sweden In Sweden tastings for presence of anti-HIV are encouraged. However, all physicians earring out the tests must be able to give psychosocial help and advice both to the afflicted and those who are seronegative but at risk. In November 1985 the HIV infection was included among the veneral diseases sub- jected to legislation. The number of tests performed and the number of posi- tive test results in this country with 8.3 million inhabitants have been re- ported since then. Up to 1987 115,000 tests (blood donors excluded) were re- ported - 10,000 thereof from homosexual men and 13,000 from drug addicts. Persons at risk were as a rule investigated several times. The number of tests performed did not decrease significantly during the period before and after legislation. However the yearly number of new sero- positive persons diagnosed declined from 856 in 1985 to 570 in 1986. The num- ber of seropositive blood donors also successively decreased from 13 in the first 530,000 tested to none of the 200,000 tested the last half of 1986. HIV-infected persons are reported from the physicians to the central epide- miological department under a code. The same code is used in reports directly from laboratories. The two report systems are in agreement with each other. M_5.6 Safer Sex and acceptance of testind.Results of the nation= wide annual servey among French Gay Men Michael POLLAK:M.A.SCHILTZ",B.LEJEUNET ‘GSPM,CNRS,Paris ,FranceTGPH, Paris,France. - An annual nationwide survey among French Gay Men(sample size: 1200) shows considerable chanqes in sexual behavior between 1985 and 1986. Number of partners has decreased, condom use has increased from 5% to 33%, more than 10% no longer practice anal sex, some 30% never did.At the same time volontary testing is widely accep= ted, as revealed by more than 30% of the respondents already tested in 1986. One out of three tested gay men being HIV-positive. Knowing ones test results does not necessarily translate into safer 'sex practices. One can rather say that the same factors are con: ducive to both safer sex and testung: — Confidence in medical authorities and past regular STD surveillance; - self confidence and social acceptance of one's homosexuality; — proximity with AIDS victims; — existence of a 'privileqed' (although not necessa: rily exclusive) love relationship that provides emotional security. Roundtable Discussion M.7 Communicating AIDS Education Across Cultural Barriers Panel Organized By: Paul Kawata National AIDS Network Washington, D.C. Panel Moderator: Gil Gerald National AIDS Network Washington, D.C. Juan Ramos, National Institute of Mental Health, Rockville, Maryland Carl Bean, Minority AIDS Council of California, Los Angeles, California Gloria Rodriguez, NJ State Department of Health, East Orange, New Jersey William Smith, Academy for Educational Development, Washington, D.C. Jaime Sepulveda, Colonia Valle, Mexico Epidemiology—AIDS in Developing Countries M8.1 Infection 10 HIV among populations of six countries of Central a Africa. ** *** t M. MERLIN , R. JOSSE , E. DELAPORTE , J.P. DURAN) , C. HH‘KSY , A.J. GEDRGESHM, *O.C.E.A.C., Yaoundé, Cameroon, **C.I.R.M.F., Gabon, *** Pasteur Center, Cameroon, **** Pasteur Institute,Bangui, Central African Republic. From 1985 to 1987, O.C.E.A.C. carried out 25 serological cluster sanple sur— veys in joint authorship with Ministries of Health of the six Metnber-states of the Organization. More than 9000 randomly selected peoples living in six countries of Central Africa (Cameroon, Central African mpublic, Glad, Congo, Equatorial Guinea and Gabon) were concerned. Rural and urban areas were investigated in different climatic zones. Various group of age were studied. "me collected blood samples were first screened by ELISA test, then positive cases were confirmed by Western Blotting. Circulation of HIV within some of the populations of the Sub—region is con- firmed, with seroprevalence rates from 0 to 5 % with Western Blotting. Heterosexual spread of HIV is the major way of infection. Under the age of ‘15 seroprevalence rates are significantly (p = 0.01) lower than those observed in adults. Each sex is equally concerned. Urban areas are very significantly more affected than rural areas (p = 0.001) Incidence rates were evaluated by the comparison of the results of several surveys carried on in the sane place after intervals of 12 or 24 months. MONDAY, JUNE 1 IH.8.2 HIV Antibody Prevalence in Migrant Mineworkers in South Africa during 1986. BRIAN A. BRINK”, R. SHER“, L. CLAUSEN*. *Chamber of Mines of South Africa, Johannesburg, South Africa. **School of Pathology, University of the Hit- watersrand and South African Institute of Medical Research, Johannesburg, South Africa. Some 512 000 employees on the Gold and Platinum Mines of South Africa are black male migrant workers recruited from various countries in Southern and Central Africa. They live in male hostels for an average of 12.7 months and return home for an average of 3.3 months. Concern about a rising incidence of sexually transmitted diseases in these employees and reports of a high prevalence of HIV infection in Central Africa prompted this study. During 1986, 330 000 blood specimens were taken at routine medical examin- ations from all migrant workers returning to work. A total of 29 961 specimens were systematically selected for HIV antibody testing, yielding unbiased samples, stratified according to country of origin. The fresh sera were screened with Abbott or Nellcozyme EIA tests and positives were confirmed by other EIA's, indirect flourescence and Western Rlotting if necessary. HIV antibody prevalence was: Malawi 119/3165 (3.76%), Botswana 7/2063 (0.34%), Mozambique 2/2152 (0.09%), Lesotho 2/2246 (0.09%), Swaziland 1/1885 (0.05%), South Africa 4/18450 (0.02%). These results confirm that there is a low prevalence of HIV infection in Southern African blacks. Malawian mineworkers have a higher prevalence of HIV infection which is probably contracted in Malawi. There is as yet no evidence for spread of HIV infection in the hostel environment. M_8_3 Risks for Heterosexual. Transmission of Hl\ in Zimbabwe David_§4VhAIZEbSTEINX.A. LAiirx,M.i.BAssuTTx,J.(. hMMAhUELtt. tUniver51ty of Zimbabwe School of Medicine and XtThe Blood Transfusion Service. Harare, Zimbabwe. In Zimbabwe, interviews with 275 HIV seropositive patients showed that contact with prostitutes (80%), multiple sexual partners (96%) and a history of sexually transmitted disease (STU) (75%) were the risks identified in 200 men. In women, 18% admitted to multiple sexual partners and 51% had a STD history. We interViewed 75 married couples in whom the husband was the seroposirive index vase. In 15 both partners were seropOSJtive (T+l; in 30 the husband was seropOSitive and the hlfe aeronegative iT—l. T+ men had more sexual partners and episodes of STD in the past two years than T- men. History of genital ulcer in male partners carried a 3 fold excess risk of seroposirivity in the female partner (T+ 7l% vs. T— 27% p «.001). Syphyllis, genital Herpes were separately associated with transmission (p (.05). r'liannroid, or Multiple sexual partners and STDS are the primary risk factors for Hl\ infection in Zimbabwe. In 60% of couples HIV transmiSSIon had occurred, associated with a history of genital ulceration in men. identification of seronegative wives of HIV seropositive men presents an opportunity to prevent infection. In_8.4 Incidence of human immunodeficiency virus (HIV) infection and rel- ted disease in a cohort of Nairobi prostitutes FRANCIS A PLUMMER, JN SIMONSEN, EN NGUGI, DW CAMERON, P PIOT, JO NDINYA-ACHOLA Kenya Medical Research Institute, Univ Nairobi, Ministry of Health, Nairobi, Univ Manitoba, Winnipeg; Institute of Tropical Medicine, Antwerp In Africa HIV is a heterosexual sexually transmitted dis‘re. Although there are many studies reporting the prevalence of HIV infic;i0i in Africa, few studies of the incidence of HIV infection and the frequency of development of HIV related illness in Africa are available. We began a study of the epide— miology of STD in a cohort of Nairobi prostitutes in January 1985. Initially 65 Z of 535 women enrolled were seropositive for HIV. All women were asympto— matic. This cohort has now been followed prospectively for two years for the development of new HIV infections and illness related to HIV. Among initially seropositive women persistent generalizd lymphadenopathy was found in 47 2 one year after enrollment. The one year incidence of more severe illness among 298 women evaluated was 5.7 Z. These included herpeszoster (8), severe vagi— nal candidiasis (3), severe weight loss (I), undiagnosed pneumonia (1) and death (3). Among women who were initially seronegative for HIV the incidence of new HIV infection was 56 Z. HIV infection is epidemic among this group of Nairobi prostitutes. Illness associated with HIV is developing at rates similar to those observed in European and North American groups. Urgent measures to control this epidemic are required. In 8_5 The Association between HIV Seroposltivity, Blood Transfusions, and Malaria in a Pediatric Population in Kinshasa, Zaire. ALAN E. GREENBERG*, P. NGUYEN-DINH*, J.M. MANN**-***, N. KABOTE****, R.L. CDLEBUNDERS**r*****, T.C. QUINN******, et 31., *Malaria Branch, Centers for Disease Control, Atlanta, GA, **Projet SIDA, Ministry of Health and Social Affairs, Kinshasa, Zaire, ***AIDS Program, Centers for Disease Control, Atlanta, GA, ****Mama Yemo Hospital, Kinshasa, Zaire, *****Inst1tute of Tropical Medicine, Antwerp, Belgium, ******Laboratory of Immunoregulation, National Institutes of Health, Bethesda, MD. To investigate the role of blood transfusions 1n the transmission of HIV among African children, we studied 1046 pediatric patients presenting to Mama Yemo Hospital (MYH) 1n Kinshasa, Zaire. Overall, 147 (14.1%) had histories of previous transfusion, and 40 (3.81) were HIV seroposltlve; there was a strong, dose-response association between transfusions and HIV aeroposltivity (p<10‘6). To study the clinical indications for blood transfusions, we reviewed 1000 MYH Emergency Ward records and found that 332/480 (69.2%) of the children receiving transfusions had malaria, and 97.32 of all transfusions were given to patients with pte-transfuslon hematocrlte of 251 or less. We then surveyed 167 hospitalized children and found that 21 (12.6%) were HIV eeropositive, 78 (46.7%) had received transfusions during the current hospitalization, and 112 (67.1%) had malaria. Ten of the 11 HIV seroposltive malaria patients had received transfusions during the current hospitalization, and four of these children were documented to have been seroneytlve prior to transfusion. The treatment of malaria with blood transfusions is an important factor in the exposure of Kinshasa children to HIV infection. In 8.6 Pattern of HIV Infection in Haiti: 1977-1986 JEAN W. PAPE*, M.E. STANBACK*, M. PAMPHILE**, R. VERDIER**,M-M DESCHAMPS**, W.D. JOHNSON, JR.*, et al., Cornell Univ. Med. Coll., NY*. GHESKIO, Port-au-Prince, Haiti**. The prevalence of antibody to HIV (wv, p24, gplZO) was determined in 246A Haitians evaluated in Port-auvPrince in 1985-1986 and in 191 Haitians bled dur- ing 3 1977-79 dengue outbreak. Among AIDS contacts, seroprevalence was highest among heterosexual sex partners (N=l7ls, 55%). Rates in their siblings and friends were higher in males (N=163, 222) than in females (N376, 92). Among un- related groups, the seroprevalence was 62 for 329 healthy urban adults - 92 in 129 mothers of sick infants, 62 in 109 hotel and factory workers, and 0 in 91 persons of higher socioeconomic status. The rate was 32 in 130 healthy rural adults including 97 mothers of sick infants. Rates among urban tbc pts. (372) were higher than among rural pts. (152). 32 of 1037 individuals who had blood tests performed in 3 commercial labs were seropositive. None of the dengue pts. bled in 1977-79 were seropositive. This pattern suggests that HIV is of recent date in Haiti, and is more prevalent in urban areas and in lower socioeconomic groups. Groups No. tested 2 Seropositive AIDS patients 384 85 AIDS pts.‘ spouses I74 55 AIDS pts.‘ sibs. and friends 244 18 Healthy urban adults 329 6 Laboratory specimens 1037 8 Healthy rural adults 130 3 Tuberculosis patients 166 22 Dengue patients 191 0 Virology—Structure and Function 11 I“ 9 1 T-CELL ACTIVATION INCREASES GENE EXPRESSION DIRECTED BY ' ' THE HIV LTR: IMPLICATIONS FOR PATHOGENESIS IN AIDS Paul A. Luciwl, Sandra E. Tong-Sarksenz, and B. Matija Peterlin2 1 University of California, Davis CA 95616, 2 Howard Hughes Med— ical Institute, University of California, San Francisco CA 94143 The human immunodeficiency virus (HIV), 3 lymphocytopathic retrovirus, is the causative agent of the acquired immunodefic- iency syndrome (AIDS). In tissue culture systems with T4 lymphoid cells, the amount of HIV replication is related to the extent of T—cell activation. We have utilized transient expression assays in the Jurkat T-cell line to investigate the effects of T-cell activation signals on gene expression directed by the HIV long terminal repeat (LTR). Promoter activity of the HIV LTR was about lO-fold greater in activated T—cells (treated with lectin) than in unstimulated cells. These activation signals are specific for the HIV LTR since expression directed by the HTLV—I LTR, RSV LTR, and HSV thymidine kinase promoter is not affected. The region encompassing the HIV enhancer appears to be the target of T-cell activation signals. The kinetics of induction of expression di- rected by the HIV LTR closely parallel those for the 11—2 and 11—2 receptor genes. The affects of of T—cell activation signals and the HIV coded transactivator (TAT) gene were observed to be multiplicative. By acting on the HIV LTR, T—cell activation sig- nals may convert a latent infection to a productive infection; thus, T—cell activation may be significant with respect to the onset of clinical AIDS in individuals infected with HIV. MONDAY, JUNE 1 ll 9 2 Mapping of the Eisfacting Regulatory Regions Responsive to the HIV ' ' £55 gene product. CRAIG ROSEN, ERNEST TERWILLIGER, JOSEPH SODROSKI. and WILLIAM HASELTINE* Dana-Farber Cancer Institute, Dept. of Biochemical Pharmacology, Harvard Medi- cal School, and *Dept. of Cancer Biology. Harvard School of Public Health, Boston, MASS. The product of the HIV §££ gene is required in trans for the expression of virion capsid and envelope proteins. However, the block in expression of virus encoded protein in virus defective for the art gene is not absoulute as such mutants can produce a functional tat gene protein. To explain the observed regulatory effects it would suffice—for the repressive sequences to be within the env gene as all of the mRNA species that encode virion g_g and any protein contain these sequences whereas the mRNA for the tat and art genes does not. To test this hypothesis we designed a novel transient gene expression assay to identify the Eisfacting determinants necessary for regulation of gene expres- sion by the EEE protein. Our reSults demonstrate that sequences that confer re- pression of gene expression are dispursed throughout the genome and that these sequences are distinct from those sequences responsive to the art product. One art responsive element, designated ARE, is present within a 40 base pair sequence that contain a highly purine— rich stretch. We propose that the func— tion of £55 is to relieve repression of gene expression that results from the presence of intragenic repressor sequences. “H‘s 3 Human Immunodeficiency virus Protease ' S. Oroszlan, T.D. Copeland, L.E. Henderson, Laboratory of Molecular virology and Carcinogenesis, BRI-Basic Research Program, “CI-Frederick Cancer Research Facility, Frederick, MD. As for other retroviruses the 222 and gggfpgl polyproteins of human immuno- deficiency virus (HIV) are processed during virus maturation by the viral coded protease which together with RT and endonuclease is translated in a —1 frame relative to the open reading frame of the 32! gene. We have analyzed the primary structure of the proteins of human T-lymphotropic virus type-III (HTLV-III) grown in H-9 cells. Proteins were purified from sucrose density gradient banded virus by reversed phase liquid chromatography. Comparison of the determined N- and C-terminal sequences with published nucleotide sequences of proviral DNA identified the proteolytic cleavage products and their order in the Prssgag and Pr170939'P°1 polyproteins. As expected the amino acid sequences around the maturation cleavage sites were found to show substantial homology. A peptide corresponding to the C-terminal sequence of HTLv-III protease was synthesized. Antibody to this peptide is now being utilized to isolate the protease in quantities sufficient for further structural and enzymological studies. HIV protease shows sequence homology to other well characterized retroviral proteases which have been shown to have an important role in virus replication and infectivity. Retroviral proteases have conserved in their sequence one of the active-site sequences of aspartylproteases and can be inhibited by certain active—site—directed inhibitors of these enzymes. (Research sponsored by National Cancer Institute, DHHS, under contract No. N01—CO-239D9 with Bionetics Research Inc.). M 9 4 Functional Analysis of the HIV A (50R) Gene Ersduct a I ' KLAUS STREBEL , D. F. DAUGHERTY , T. M. FOLKS , K. A. CLOUSE , M. A. MARTIN‘. "Laboratory of Molecular Microbiology, and “"Laboratory of Immunoregulation; National Institute of Allergy and Infectious oDiseases, NIH, Bethesda, MD 20892; *‘University of Michigan, Ann Arbor, MI.; °Georgetown University, Washington, DC. We investigated the biological function of the HIV A-gene product by using a mutant of an infectious clone containing a 620 bp deletion in the A gene region (pAA) . when the infectious molecular clone of HIV and the AA mutant were separately transfected into the SW480 colon carcinoma cell line, the production of virus particles (as monitored by RT) was readily detected, but a cell-free lysate, containing AA progeny virus, could not he passaged into T4+ lymphocytes. In contrast, the AA HIV infection could be transferred to T4+ lymphocytes by cocultivation. To ascertain whether the A gene product could function in trans, cDNA clones expressing the A protein were cotransfected with the AA mutant and the resulting filtrates were evaluated for their infectivity in T4+ lymphocytes. In all cases examined, the AA mutant could be complemented with constructions expressing the A gene; however, the progeny virus from these cultures could not be repassaged in 14" lymphocytes. These observations suggest that deletion of the A-gene results in the production of particles that are apparently defective at an early step during their replication. m_g.5 The role of the E gene of HTLV-III/HIV AMANDA FISHERl, B.Ensol11, L.Ivanoff2, L.Ratner3 1. F.Hong-Staal1 1 Laboratory of Tumor Cell Biology. NCI, NIH, Bethesda, MD 20205 E.1.Dupont. willm1ngton, Delaware 3 Division Hematology 81 Oncology, Washington University, St.Louis, MI 63110 The role of the sor gene of HTLV- III/HIV and its product is not known although 1n1t1al reports have indicated that it, like 3' orf is dispensible for replication (Sodrosk1,1986). To 1nvestigate this—.— 1ssue we constructed a series of variants of HTLV- III in which either the entire cod1ng sequences of 501‘ had been removed or term1nation codons had been introduced into the sor r_ead1ng frame by site directed mutagenes1s. These mutants were capable B'f'generafing v1rus particles upon upon transfect1on. However, all the mutant clones were extremely l1m1ted in their capaciy to establish stable 1nfect1on in vitro ; less than 1% of cells consistently expressed HTLV- III antigen in cultures infected with sor mutant v1 ruses as opposed to 80-90% of cells 1n controls (all cultures We monitored for 8-12 weeks). Analysis of cos-1 cells transiently transfected with the mutated clones showed no change 1n either the quantity or quality of viral RNA, protein or particle expression. Further- more the ab1l1ty of these clones to trans- activate rema1ned unaltered when tested 1n lymhoid and in nonlymphoid cells. These data argue that (1) the sor gene has an important biological role undulating v1rus propagation W (11) that this gene most likely acts at a post translational level. M g 5 Direct mtagenesls Analysis of the Trans—Activator Genes of Human ' ' T Cell Lynphotropic Virus Type III M. REZA SADAIE, T. BENTER and F. me-STML, Laboratory of Tumor Cell Biology, Naf1ona| Cancer Institute, NIH, Bethesda, Maryland 20892. Himan T- lymphotropic virus is unique in containing multiple non- structural genes that are regulatory in function. Two of these (tat- Ill and trs) have been shown to be essential for virus replication based—En deletion mutant studies. However, independent roles of these genes in regulatlon of virus rep- lication have not been elucidated previously. In this study, we used the ap- proach of site directed mutagenesls to generate point mutations in desired nu- leotide positions. We obtaind a panel of tat and trs mutants and evaluated their functions by the following parametefi tranfilption, steady—state mRNA levels, protein synthesis and virus production. The following conclusions could be drawn: 1) Tat-III has a positive trans-acting role In both transcrip- tional and post-trafiriptional events. 2) A chain terminating mutation 1n the trs gene rendered the provirus defective resulting In a grossly modified viral s_pT1c1'ng pattern and unusually high levels of the viral 1.8 Kb mRNA species. Therefore, trs gene product may have a negative trans-acting role in regulat- ing the levFl—of the 1.8 Kb mRNA species. 3) Point mutant prov'lruses defective in tat or trs were complemented by a wild type tat and trs cDNA subclone al- lovdng thefitants to resume the nonnal transcr'lpfion pE'E'fern and subsequent virus production. 4) Both tat and trs function in a co-operative manner regu- lating the virus replicat‘IW, 1.e.fioth gene products are required for optimal trancrlptlon and translation of the viral structural genes. Immunology—Viral Proteins and Virus Speclfic Immune Responses Analysis with recombinant vaccinia viruses of CD4/HIV gp intaictkn M'1o'1 within individual cells. P.SALMON,R.OLIVIER,Y.RIVIERE,M.P.KIENNY,L.MONTAGNIER,J.C.GLUCKMAN,D.KLATZMANN. UFR Pitié—Salpétriere and Institut Pasteur,Paris,Transgene,Strasbourg,FRANCE. Interaction between HIV gp and CD4 occurs during virus—cell contact (tro— pism),during cell-cell fusion (syncitia) and,though less well documented,within individual cells (cell death?).In infected cells,the selective and progressive disappearance of CD4 at the membrane,contrasting with conserved CD4 mRNA levels and intracytoplasmic CD4/gp complexes have been noted, suggesting their causal relationship with cell death. We further investigated this point by infecting CD4+ lymphocytes with various recombinant vacdnia viruses that contained nomal cr nu- tated, partial or complete,§fly gene. Expression of various membrane markers,and gpthection with MAb, was assessed by cytofluorometry on viable cells.Progres— sive and complete disappearance of Leo 3a staining associated with a 3 to 10 fold decrease of OKT4 fluorescence intensity correlated with increasing expres— sion of gp, which indicates both reduction in the number of CD4 molecules at the membrane and their complexing with gp. Surprisingly, expression of the "na— tural" HIV gp 110—41 had no effect, and only uncleaved gp 160 or normal gp llO directly anchored in the membrane through its linkage to a homologous or hetero— logous transmembrane protein induced such effect. As after "natural" HIV in- fection, we could inmunoprecipitate intracytoplasmic CD4/gp complexes and show- ed unchanged CD4 mRNA but no cell fusion. Thereforelduring "natural" infection of CD4+ lymphocytes, while few cells express viral antigens, complete CD4 modu— lation indicates that all cells are finally infected, which directly leads to their death.0ur results are relevant to the selection of the proper recombinant for vaccination or innmne response analysis, and to understand the CD4/gp ccnr plex formation and cell death. MONDAY, JUNE 1 “n_10'2 Analysis of HIV Protein Presentation on Infected Cell Surfaces: Evidence for Group, Type, and Host Cell Specificity. §I§PHEN G. CARTER‘, ".6. HOBEY**, L.0. AHTHUH*, P.J. FISCHINGER**, AND M.A. GONDAt, *Program Resources, Inc., NCI—FCHF, Frederick, MD, *toffice of Director, National Cancer Institute, NCI-FCRF, Frederick, MD Development of a successful vaccine against HIV requires the identification of proteins on the virus envelope and cell surfaces involved in the immune recognition process. Antibodies were prepared to purified proteins (core and envelope) from HIV (strain HTLV—IIIB) and analyzed by flow cytometry. Anti— bodies to glycosylated or deglycosylated forms of gp120 bind to HTLV—IIIB— infected H—S cells, although those against the deglycosylated gp120 react to a lesser degree. Antibodies to gp41, the transmembrane protein, also recognize small amounts of gp4l. A polyvalent, monospecific antiserum to p24, the major core protein, did not detect any epitopes on HTLV-III-infected H-9 cells. These results suggest that epitopes of gp41 and glycosylated and nonglycosy. lated gp120 are involved in the immune recognition process. Thus, they may be important in evoking protective antibodies, whereas epitopes of p24 may not. We also investigated the reactivity of a sequential series of bleeds from a goat inoculated with HTLV-IIIB gp120 isolated from infected H~9 cells with various isolates (envelope strains) of HIV growing in H-S cells. Both type— and group-specific antibodies were demonstrated by flow cytometry, with the type—specific reactivity occurring (early bleeds) prior to the detection of group-specific (late bleeds) reactivity. Unexpectedly, these antisera showed a marked reduction in reactivity with HTLV—IIIH grown in Molt-3 cells, another human lymphocyte. This reduced reactivity could not be attributed to a lack of production of viral antigen; but rather may reflect cell-specific processing of gp120. Cell—specific processing of gp120 should be investigated further as it may directly influence the immune recognition of envelope preparations. Id 10 3 Cellular Immune Response to Viral Peptides in Patients Exposed to ' ' HIV. PAUL M. AHEARNE*, K.J. WEINHOLD*, T.J. MATTHEWS*, S. PUTNEY**, S. PETTEWAYf, N. Chang++, et al. *Department of Surgery, Duke University Medical Center, Durham, NC, **Repligen Corporation, Cambridge, MA, fCentral Research and Development Department, E.I. DuPont de Nemours & Company, Wilmington, DE, ++Center for Biotechnology, Baylor College of Medicine, Houston, TX. In order to study anti-HIV cellular as well as humoral reactivity in AIDS patients, we measured the proliferative response of peripheral blood lympho— cytes to a purified native gag p24 and four recombinant peptides representing various regions of the env gene. These peptides include Penv3 (gp120 amino terminus), PBl (gplZO midportion), Penv9 (gplZO carboxy terminus + a portion of gp41) and p121 (gp41 subportion). The patients were characterized by their HIV antibody status and general immunocompetence as reflected by the EB vitro response to tetanus toxoid (TT). P24 elicited 33 vitro blastogenesis in seropositive TT responders but not in TT non—responders nor seronegative controls. Fifty percent of the patients showed humoral reactivity to p24. All seropositive (Western) patients expressed strong humoral reactivity to Penv9 and p121 in contrast to the weak cellular stimulation to these two peptides. PBI elicited a variable humoral response and little if any cellular response. In sharp contrast to the very weak humoral stimulation, the most impressive cellular response was to Penv3. This showed good cellular reactivity in IT responders, slightly decreased reactivity in TT non—responders and poor reactivity in controls. The cellular response to Penv3 seems to continue after loss of TT reactivity; whereas, the immune response to the core protein p24 is decreased with loss of TT reactivity. These results suggest that regions of gp120 which are recognized by cellular elements (Penv3) may differ from those that stimulate a humoral response (Penv9). MH104 Cellular immune response and neutralizing antibodies towards HIV In infected individuals. SATU MATTINENs. A. RANK1**, v.6. ROBEY as”, J. ANTONEN! AND K.J.E. KROHN«,**, *Institute of Biomedical Sciences, University of Tampere, Finland. nflLaboratory of Tumor Cell Biology, NCI, Bethesda, MD, *xIFCRF, NCI, Frederick,MD. To study the relevance of Immune response towards HIV to the progression of the disease we measured neutralizing antlbodles and T cell responses to purified HTLV-III protelns gp120 and p24 as well as to Inactivated whole vIrIons In 28 HIV Infected Individuals. Neutralizing antlbodles, capable of preventing the cytolytlc effect of HIV on a sensltlve target cell line, ATH—B, were seen In 66% of the cases. The presence of neutralizing actIvIty correlated wlth western blot conflrmed antlbodies to gp120, gp41 and p17. In T cell prolIferatlve assays, a few Indivlduals responded to p24, but no response to the whole vIrIons or to gp120 was seen. not even In cases having remained asymptomatic for 3 years. Prevention of the vlral repllcation with 2’,3’—dldeoxyadenoslne dld not Increase responsiveness. Moreover, fin ' hybrldlsatlon revealed only a few Infected cells (10‘ . 10' ), morphologically belonging to the monocyte — dendrltic cell lineage. We have shown that the early energy to soluble recall antigen: In HIV Infection Is due to Infection of the above cells, but In the present materlal even persons showlng normal PPD response had HIV speclfic energy. The possiblllty, that man has an Inborn tolerance to the T cell epltopes In HIV external envelope. can be disproved only by direct Immunization experlments. HH.10.5 Common and Variable Neutralization Antigens of HIV-1 and HIV-2 PAUL R. CLAPHAM*, J.N. WEBER*, L. MONTAGNIER**, R.A. WEISS*, *Institute of Cancer Research, Chester Beatty Laboratories, London. ** Unite d‘Oncologie Virale, Institut Pasteur, 25-28 rue du Dr. Roux, 75724, Paris Cedex 15. We have shown that sera from HIV-1 infected individuals are capable of neutralizing a genetically diverse range of HIV—1 isolates (Nature, ggg, 572- 575, 1986). Some HIV-1 isolates (e.g. ARV-2) are far more sensitive to neutra- lization than others. Sera from HIV-2 infected individuals will cross-neutralize some isolates of HIV-1 but the neutralizing titres are significantly lower than those in the sera of HIV-1 infected individuals. HIV-1 sera fail to cross—neutralize the LAV-Z isolate of HIV-2. However, this isolate is poorly neutralized by autologous sera, and low-titre cross-neutralization would be missed. The identification of common neutralization antigens between diverse HIV strains is important for vaccine development. In 10 6 Antibody-dependent cellular cytotoxicity (ADCC)-1nducinq antibodies ' ' against human immunodeficiency virus (HIV). Kristina Ljunggren*, E-M. Fenyo**, B. Bottiger***, G. Biberfeld*** and M. Jondal*. Departments of Immunology* and Virology** at Karolinska Institute, Department of Immunology*** at National Bacteriological Laboratory. Stockholm, Sweden. A method to detect antibodies which mediate HIV-specific ADCC was established using HIV infected monocytoid U937 (clone 2) cells as targets. Simultaneously, the ADCC efficiency of the allogeneic effectorcells was tested with rabbit- anti-b2 microglobulin serum against the same U937 cells. It was found that approximately 40% of all anti-HIV positive sera could induce ADCC killing, irrespective of the clinical stage of the donor. Quantitative comparison of ADCC titers of sera from patients with different severity of HIV infection showed that high HIV specific ADCC titers were more common in symptomfree patients (75%) than in AIDS patients (42%). When the T4:T8 lymphocyte ratio was compared to ADCC titers, no correlation was found. Sera from AIDS patients which had lost antibodies to gag(p19,p24) and pol (p55) proteins, but which were still positive for gp160, 120 and 41, could mediate ADCC. In further studies, the fine specificity of ADCC active antibodies will be defined using target cells infected with recombinant virus expressing part of the envelope antigens. Also, evaluation of the clinical significance of HIV- specific ADCC antibodies will be needed. Clinical Management—Cancer, Hemophilia and Cardiovascular Disease In 11 1 The Clinical, Research and Public Health Applications of the Walter ' ' Reed Staging Classification of HIV Infection R REDFIELD WRAIR Wash DC In 1985, the Walter Reed Staging Classification of HIV infection was proposed. This staging scheme recognizes that HIV infection as an etiologic disease process in which the central pathogenic event resulting in immunodeficiency is the progressive destruction of the T helper cell population. In addition this scheme recognizes that central nervous system disease, complicating neoplasms, chrombocytopenia and severe constitutional symptoms may have pathogenic mechanisms of occurrence secondary to HIV but independent of functional intregity of the T cell system. The purpose of this talk Is to describe the proper excecutlon of this system, and to demonstrate its multiple applications outlined below. Data will be provided demonstrating its usefulness for each. I) ROUTINE CLINICAL: a) uniformity of clinical evaluation among health care system; b) pathogenic based framework to clinically approach, manage and follow patients; c) prognostic predictor for physician and patient; 2) RESEARCH: a) facilitate an understanding of the natural history of HIV infection; b) facilitate an understanding of the pathogensis and effect on outcome of associated disease processes; c) facilitate an understanding of the immune response to HIV and its biological significance; d) facilitate the evaluation of therapeudlc modalities; e) facilitate an understanding of the efficiency of transmission of different modes and stages of infection; 3) PUBLIC HEALTH: 8) facilitate accurate survalence of HIV infection and disease; b) facilitate accurate determination of the incidence of infection; c) facilitate early case identification; d) facilitate the implimentation of public health control programs; e) facilitate the evaluation of the effectiveness of public health invention stragities. MONDAY, JUNE 1 M.11_2 Update on AIDS—Associated Non-Hodgkin‘s Lymphoma (NHL) in San Francisco. LAWRENCE D. KAPLAN, PA VOLBERDING, DI ABRAMS, Dept of Medicine, San Francisco General Hospital (SFGH), UCSF Cancer Research Institute, SF, CA, USA. Forty homosexual men with NHL were treated at SFGH 10/82—12/86. Serologic studies performed in 28 patients revealed all 25, including all surviving patients, to be HIV seropositive. Histologic pattern included small noncleaved (5295), large cell (45%) and cutaneous T—cell (2.555) . Patients presented witn Stage IV disease (75%), Stage III (15%), Stage II (7.596), and Stage IE (solitary lung nodule) in 596. Extranodal sites included bone marrow (10) meninges ('1). liver (5), lung (3), stomach (4), epidural (2), soft tissue (2), nasopnarynx (1), other G: (3). Thirty—one were treated with aggressive chemotherapy and 2 received primary radiation therapy. Treated patients without a prior AIDS diagnosis (25) had a complete response (CR) rate of, 56% and a median survival of 18.5 mos. Those with a prior AIDS diagnosis (10) had a CR=16% and a med: n survival=2.9 mos (p=0.04 for survival). There was a direct relationship between relative dose intensity and freedom from relapse. Significant dose reductions were required in 6/9 or those with prior AIDS diagnoses, due to severe marrow suppression, opportunistic infection, or both. While aggressive therapy does prolong survival in some patients, those with prior AIDS diagnoses are less efy to tolerate such therapy, to achieve CR, and to remain disease free. M11_3 Clinical Course and Epidemiology of Hodgkin's Disease (HD) in Homosexual Men in San Francisco (SF) . Mimics D KAPM, DI ABRAMS, PA VOLBERDING, Dept of Medicine, “ co ~ .eral Hospital (SFGI-i), Cancer Research Institute Sen :3 UCSF, San Francisco, CA, USA. Thirteen homosexual men with ED have been diagnosed and treated at $96 between 5:83 and 12j86. All 9 patients tested were HIV seropositive. 9 (70%) had a prior b’story of generalized iymphadenopathy or thrusr and no patient had a prior AIDS diagnosis. Mixed celluLarity histology was present in 9 (70%), nodular sclerosis (NSED) in 3 (23%) and i was unclass d. Stage III or IV disease was presenf in 12 (92%) with bone .a: ow involvement in 9 (70%). Five (38%) were treated with. M P? and 7 (62%) with MOPEABVD. There were 7 (54%) complete responses, and one of these relapsed. PCP developed in a (6295), M. avium in 1 (8%). Three patients (30%) remain live with active disease at 1,5,. and 15 mos from diagnosis. Only one (8%) is disease—free at 24 mos. We compared this group to 35 cases of HD in never— married 5? males, age 20-49 diagnosed between 1973—1979. 22 (63%) were N533 and 8 (23%) were MCHD. Twenty—five (70%) had Stage III or IV disease. 21 patients (60%) and 13 (52%) of those with stage III or IV disease have survived disease free >5 yrs. The incidence of HD in this SF population has not increased during the period 1980—1985 (relative risk .2,1985), suggesting a lack of correlation between E v :.'ect . and development of ED. However, our c; cal data suggests a marked alteration in the natural history 0 ID in HIV—infected indil‘ uals, anfi thus, the importance of serologic testing in this group. c, “n 11.4 HIV Isolation from Hemophiliacs: Immunological and Clinical SCUdies. CHARLA ANDREWS, J. Sullivan, D. Brettler, A. Forsberg, F. Brewster, P. Levine. University of Massachusetts Medical Center, Worcester, MA. As part of a prospective study of human immunodeficiency virus (HIV) infection in hemophiliacs, blood from 72 individuals without AIDS or ARC was cultured for virus. HIV was isolated from 15 out of 66 (232) hemophiliacs who were seropositive for HIV, and none of 6 seronegative patients. Virus positive hemophiliacs had significantly reduced T-helper cell numbers, T- helper/T-suppressor ratios, pokeweed mitogen (PWM) responsiveness, total platelet count and a higher incidence of thrombocytopenia ((150,000/ul) when compared to virus-negative patients. MEAN DATA FROM SEROPOSITIVE HEMOPHILIACS HIV T-helper T-helper/ P’WM Platelets <150,000(%) isolation g cells ul T-sugpressor (cam Pltlul platelet/ul + u. 393., .603 7M8 187,000,‘ 7/11. (50%) , 763’ .2306“ 12910” 236,137‘ 9/51 (9.3%)" - 51 *p<.001; # p<.05 , The seropositive, virus-positive hemophiliacs also presented with more severe clinical findings than virus isolation negative hemophiliacs. One virus— positive hemophiliac developed AIDS during the study. The mean neutralizing antibody titer did not differ significantly between the virus-negative and virus-positive hemophiliacs. HIV was recultured from 5 out of 6 hemophiliacs up to 1 year later; 9 virus-negative hemophiliacs remained negative for HIV when re—cultured. The significant decrease of T-helper cells and the presence of thrombocytopenia in 502 of the virus-positive group may be a reflection of a heavier virus load, and might be an early marker of more unfavorable prognosis. I“ 11.5 International Surveillance for HIV Seroconversion in Hemophilia Patients Receiving Heat—treated Factor Concentrate Therapy. DALE N mmucal, s SCHULMANZ, c R 11122113, T mm“, E P MAUSER- BUNSCHOTENS, K RICKARDG, et 31., 1Centers for Disease Control, Atlanta, GA, ZSwedish Hemophilia Fdn, Stockholm, 3 Oxford Hemophilia Ctr, UK, 4H0pital Bicetre, Paris, FR, 5Van Creveldclinic, 311thoven, NL, 6Royal Prince Alfred Hospital, Sydney, AUS, et al. Scattered reports in 1986 described HIV seroconversiona in hemophilia patients receiving heat-treated factor concentrates (HtFC) produced before donated plasma was screened for HIV antibody. In late 1986, 14 regional and national hemophilia treatment centers in 7 countries of Europe and North America and Australia collaborated to characterize their seroconverters and to quantitate the risk associated with unscreened and screened HtFC. Most of the 1300 seronegative patients under periodic serologic surveillance had previously received unheated PC. of 450 initially seronegative severe hemophilia A patients, three children still aeronegacive 6 months after the exclusive use of (unscreened) HtFC, seroconverted thereafter (0.72 of hemophilia A; 0.2% of total). The latest seroconveraion was in November 1985. All 3 are asymptomatic, but at least 1 has severe T cell abnormalities and at least 1 other was HIV culture—positive. To provide reliable estimates of the risk of HIV eeroconversion associated with screened HtFC which was introduced in these centers between August 1985-July 1986, continued collaborative surveillance is underway to accunulate adequate numbers of patient-years of such therapy. To date, no seroconverslons have been noted in nearly 400 patient-years of therapy. By May 1987, the aggregate total for the centers will exceed 1500 patient-years, allowing analysis by type of hemophilia and severity level. M 11 6 mac Pathology and Cardiovascular cause of Death in Patients ' ' Dying with the Acquired Inmmdeficiency Wane (AIDS) plw wgnllunmsow, R. VIRMANI‘, A. M. m*, 'r. O'LEARY“, M. mammary, w.c. ROBERTS“. et al., *Azmed Forces Institute of Pathology. Washington, DC and “Carddmrascular Pathology, NHLBI, NIH, Bethesch, MD. The preserwe of cardiac pathology was retrospectively evaluated at necropsy in 82 patients dying with AIDS in the USA between 1981 and 1986. Myocarditis (MYO), defined according to the Dallas criteria as myomrdial necrosis surrounded by inflamnatory cells, occurred in 40 (5096) cases. Opportunistic myolzxdial pathogens were seen in only 14 cases (ngondii-a, H... capsulamn-S: 9.. mofomans-3 E... cation-1. cvtarlegalovims-2. and tera app-2). Dilated cardiaayopathy was diagnosed at necropsy in the presence of biventricular dilatation without significant coronary or valvular heart disease and occurred in 7 (9%) patients, all of kiln manifested MYO. In contrast, right ventricular dilatation in the absence of biventricular dilatation was found in 14 (1796) cases and was associated with riglt ventricular hypertrophy (p<0.05), perimrdial effusion (p<0.01) and amortunistic pulmonary infections (p<0.05) but thXO (p >o.os). A clinical cardiovascular cause of death was established in 7 (996) cases and included 6 patients with we (refractory ventricular tachycardia-1. dilated dazdiomyopathy with congestive failure—4, and swan death-1). Epicardial Kaposi‘s sarcala occurred in 9 (1096) cases and was generally not clinitally significant. Hovever, in one case extalsive pericardial and periaortic involva'rent led to hempericaxdium and death from cardiac tamponade. Conclusion: Myocarditis is a frequent necropsy finding in tatia'lts dying with AIDS and my lead to fatal dilated caniiomyopathy in this population. Roundtable Discussions M.12 Prevention and Control of AIDS in Developing Countries Kenneth Bart Agency for International Development Washington, D.C. Panel Moderators: M. Mukunyandela Tropical Diseases Research Centre Ndola, Zambia Donald Forthal, Department of State, Washington, D.C. Anthony Meyer, Agency for International Development, Washington, D.C. Bahman Habibl, National Center for Blood Transfusion, Paris, France T. Stephen Jones, Centers for Disease Control, Atlanta, Georgia King K. Holmes, Harborview Medical Center, Seattle, Washington James Shelton, Agency for International Development, Washington, D.C. MONDAY, JUNE 1 M13 The Status of Screening: Supplementary Tests for HIV Infections Thomas F. Zuck Food and Drug Administration Panel Organized By: Rockville, Maryland Panel Moderator: Ian Gust Fairfield Hospital Melbourne, Australia Panel Members: Experts from the United Kingdom, Europe, North America and Australia M.14 AIDS and the Media Panel Organized By: Terry Beirn American Foundation for AIDS Research New York, New York Susan Freinkel, Wichita Eagle—Beacon, Wichita, Kansas Herculamo Siqueira, Denison Advertising, Rio De Janeiro, Brazil Allen Wurtzel, ABC, New York, New York Ellen Levine, Women‘s Day Magazine, New York, New York Diana Kerew, Diana Kerew Productions Inc., Los Angeles, California J. G. M. Jagwe, Uganda National Committee on Prevention of AIDS, Entebbe, Uganda Poster Session MP1 INHIBITIDN OF REPLICATIDN 0F HIV 8V AVAROL AND AVARONE w;E.G; MULLER*, H=C. SCHRDDER' and P.S. SARIN# *Institut fur Physiologische Chemie, Universitat, 0-6500 FRG and #Laboratory of Tumor Cell Biology. National Cancer tute, Bethesda MD 20892. The sesquiterpenoid quinone avarone and its hydroquinone evarol, two natural products from the marine sponge Dysidea avara, have been identified as cyostatic agents that preferentially inhibit growth of T cell lymphoma lines (1). In the present study it is shown that these compounds have a dose-dependent inhibitory effect on the replication of HIV in H9 cells in vitro (2). Both compounds show a significant cytoprotective effect on HIV infected H9 cells at concentrations as low as 0.1 pg/ml (0.3 MM)? At this concentra— tion, no inhibitory effect is observed in human or murine periphe- ral blood or spleen lymphocytes (3). Both avarol and avarone block in a dose-dependent manner the expression of the HIV gag proteins p24 and p15 in the infected H9 cells, and block viral replication as judged by approx. 80% inhibition of reverse transcriptase acti- vity. The potential usefulness of these compounds in the treatment of patients with AIDS and ARC is supported by their following pro— perties (3): "T-lymphotropic“ cytostatic activity, B—lymphocyte activating property, antimutagenic activity, low toxicity in mice, high therapeutic indices, and penetration of the blood-brain barri- er. A clinical trial to determine the potential antiviral effect of avarol in patients with AIDS is in preparation= (1) M011er,w.E. G. et al.(1985) Cancer Res: 45, 4822; (2) Sarin,P.S.,Sun,D., Taguchi,V. and Muller.w;E:G.(1933) J. Natl: Cancer Inst..in press; (3)MUller,w.E.G. et al.(1986)Eur.J.Cancer ClinIOncol. 33,437 Mainz. Insti- 10 MR2 AIDS Subacufe Encephalitis : Identification of fl] Infected Cells ROSEMAY VAZEUX', N. BROUSSE", A. JARRY", L. MONTAGNIER', M.BRAHIC'. 'Institut Pasteur. Paris, “Inserm U239, Faculle Xavier Bichat, Paris. France Human iflmunodgficiency virus (HIV) RNA and proteins were detected in 5 brain tissues to 12 AIDS patients with subacule encephalitis. using in sifu hybridization and immunohistological labeling with monoclonal antibodies against p18, p25. gp41 and gp110. Staining patterns were superposable with the 2 techniques. A massive and diffuse HIV infection, with clusters of fl/ infected cells present in almost every tissue block studied, including spinal cord. was correlated with severe demence and was detected in 3 of these 5 HIV infected palients. The majority of infected cells were mononucleated and bore processes. Using single and double immunohistological procedures, we identified these cells as macrophages Leu M5+, EBM 11+, KB 90+, 9.4+. HLA-DFl+. T6-, DRC-. The majority of them had the phenotype of normal resident brain macrophages/microglial cells (Leu M3-, 004-), others were labeled with markers of circulating macrophages (Leu M3+, CD4+/-), were present in Inflammatory infiltrates and microglial nodules. and were associated with a few infected CD3+/CDa- T cells. We could not detect any Infected astrocytes or neurons. all Infected process bearing cells were labelled with macrophage markers thus it is very unlikely that oligodendrocyfes were infected. Effect of Diethylcarbamazine Feline Leukemia Virus Infected Cats LVNN ll. KITCHEN, Harvard School of Public Health, Boston, MA. Eight cats (2 sets of littennates) testing positive for feline leukemia virus (FeLV) antigen in perlpheral blood leukocytes were entered into prospective trials to evaluate the therapeutic effect of oral dfethyl- carbamazine citrate (DEC). Twenty-two additional healthy outbred FeLV cats were also treated with DEC. Pre and post treatment serum viral infectivity was determined for 24 treated cats. Fourteen of these 24 treated cats (58%) initially presented with high titers of serum infectious vlrus by the assay of Flschinger. Serum viral infectivlty became undetectable 1 month after initiating treatment in 12 cats, after 90 days in 1 cat, and after 300 days in 1 cat. Nine cats initially testing negative ((1:10 dilution) for antibody to feline oncornavirus associated cell membrane antigen (FOCMA) tested positive after treatment. Average survival was prolonged by 3 months with DEC treatment In 2 FeLV-inoculated cats in comparison to 2 untreated controls. Survival among cats treated without prospective controls was improved In comparison to an historical control study. DEC treatment has prevented lymphopenia (to date, age 9 months) in 2 naturally- 1nfected FeLV kittens; 2 untreated llttennates have both developed lymphopenla. Our results may have implications for humans infected with inmunosuppressive retroviruses. on MP.3 Anti—HIV Activity of 3'-Subst1tuted-2'.3'-Dideoxythymid1ne Analo- gues MP.4 RUDI PAUWELS, M. BABA, J. BALZARINI, P. HERDEWIJN, E. DE CLERCQ and J. DESHY- TER, Raga Inetitutn for Medical Research, 3-3000 Leuvcn. Belgium. In MT—A cells 3'—az1do—2',3'—d1deoxythym1d1ne (AzddThd, AZT) inhibits HIV replication at 0.06 pH, that is at a dose 50—fold lower than in ATHB cells (1-5 uM). No such increased activity was observed for 2',3'-d1deoxycyt1d1ne and 2',3'-d1deoxyadenosine when evaluated in MT-A cells. Therefore, this cell line was used to determine the structure-activity relationship of newly syn— thesized 2',3'-dideoxythymid1no analogues modified in the 3'-posit10n. From this study AzddThd, ddThd end its 2',3'-unsaturated derivative ddoThd emerged as the most potent inhibitors of HIV (complete protection at 0.04, 5 and 0.2 uM. respectively) with an almost identical selectivity index. 3'- Fluoro—ddThd effected 10—40 2 protection at 0.008 uM but proved extremely to- xic. None of the other 3'-helogenated derivatives of ddThd (1.e. 3'-chloro-, 3‘-bromo-, 3'-1odo—ddThd) had a significant HIV-inhibitory effect. The 3'-0- mesyl derivative of ddThd effected 50 Z protection against HIV at a concen- tration of 5 uM without any toxicity at 125 uM, whereas other 3'—0-11nked subotituenta (i.e. 3'-methoxy, 3'-ethoxy, 3'—0-carboxymethy1) virtually anni- hilated the entiretrovirel affect of ddThd. Substitution of - thiocyeno group at C-3' of ddThd led to a similar protective activity as seen with 3'-0-me— syl-ddThd, but 3'-th10cyano-ddThd proved also cytotoxic. 3'-Ethy1thio— and 3'—hydroxyethylth1o—ddThd were less active than 3'-thiocyano-ddThd. Our stu- dies thus revealed that any substituent at the C-3‘ position of ddThd, with the exception of azido, considerably decreased the entiretroviral effect of ddThd, suggesting a critical function of this part of the molecule in its in— teraction with its target enzyme(s). Katholieke Universiteit Leuvon, MONDAY, JUNE 1 MR5 Mismatched Double-Stranded RNA (Ampligen) Protects Target Cells from HIV Infection and Reduces the Concentration of 3'-Azido- 3'Deoxythymidine (AZT) Required for Virustatic Activity. WILLIAM M. MITCHELL, DAVID C. MONTEFIORI, W. EDWARD ROBINSON, and WILLIAM A. CARTER, Vanderbilt University, Nashville, Tennessee, and Hahnemann School of Medicine, Philadelphia,Pennsylvania. The biological response modifier rln~r(C12~U)n, generally referred to as mismatched double-stranded (ds) RNA or Ampligen® was able to protect target lymphoblastoid cells in vitro from infection by the human immunodeficiency virus (HIV). Significant protection of the highly HIV-permissive T-cell line C3 is observed with Ampli en in the 10-50 pg/ml concentration range, Similar results are observed at 50 pg/m in CEM cells. When administered simultaneously with sub-virustatic concentrations of azidothymidine (AZT), protection of target cells from HIV infection is increased. At higher doses of AZT tested, the virustatic activity observed appeared to be in a synergistic virustatic relationship with Ampligen. Moreover, in combination with Ampligen at least a five-fold reduction in AZT concentration can be used in order to obtain equivalent virustatic activities. Thus, combined therapy with Ampligen and AZT can be expected to be more beneficial to ARC or AIDS patients since current AZT regimens of apparent clinical effectiveness are associated with significant toxicities which undermine its therapeutic potential. MP3 Modification of HIV N-Glycosylation by the o-Mannosidase Inhibitor Swainsonine. DAVID C. MONTEFIORI, W. EDWARD ROBINSON AND WILLIAM M. MITCHELL, Vanderbilt University, School of Medicine, Nashville,Tennessee. The two envelope glycoproteins (gp41 and gp120) of human immunodeficiency virus (HIV) serve functions obligatory to the pathogenesis of HIV including attachment of virus to tar et cells and syncytium formation. Swainsonine is an indolizidine alkaloid foun in certain legumes and molds and alters protein N- glycosylation through its potent reversible inhibition of a-mannosidase II (Broquist, H., Ann. Rev. Nutr. g, 391-409, 1985). Our interest has been to investigate the si nificance of N-glycosylation in HIV pathogenesis using swainsonine and other in ibitors of glycoprotein processing as tools. We have found that swainsonine affects N~glycosy|ation of HIV glycoproteins without affecting virus yields. The concentrations of swainsonine utilized in these studies (1-10 pg/ml) had no effect on cell division or RNA and protein synthesis. Synthesis of virus in the presence of swainsonine was confirmed by reverse transcriptase activity in culture fluids and by density gradient centrifugation of [355] methionine labelled virus. Results of [3H] mannose labelling experiments and SDS-PAGE/fluorography demonstrated that swainsonine causes a reduction in the molecular weight of the HIV envelope gp120 reducing it to a gp'I 10 molecule. MR'] Comparative Study of Human Immunideficiency Virus (HIV) Strains VICTOR M.ZHDANOV, D.I.Ivanovsky Institute of Virology, Moscow, U.S.S.R. Human immunodeficiency virus (HIV) strains received from Fran- ce and the U.S.A. and isolated in the U.S.S.R. (including indi— genous and imported from Africa) were comparatively studied. In experiments with monoclonal antibodies a sertain homogeni- city of both standard and African strains was shown, and some difference of indigenous strains isolated in the U.S.S.R. was marked. Restriction analysis showed a more marked variability of the strains studied, although in experiments with molecular hybridi- zation they appeared to be more homogenous. This points to a high frequency of neutral mutations that do not affect amino- acid composition but do affect recognition sites for restriction endonucleases. Plasmids were obtained that contain non-infectious genome of HIV with removed LTRs and provirus was sequenced. Variations were revealed within all genes, particularly in env region. A hypothesis is proposed about the existence of a Northern HIV variant with low virulence as compared with American and African viruses. The virus causes predominantely asymptomatic infection. 11 MP3 HIV propogates in human neuroblastoma cells PAUL SHAPSHAK, D.T. IMAGANA, K. SANO, F. CALLEGARI, K. SUGITA, M. LEE, et.al., Harbor-UCLA Medical Center, Torrance, CA 90509 & Neurology Service, VAMC, Wadsworth Division, Los Angeles, CA 90073, U.S.A. There is evidence that HIV is neurotropic and that its persis- tence in the CNS is associated with AIDS encephalopathy and dementia in order to characterize HIV persistence in vitro, this laboratory undertook the propagation of HIV in four cell lines, two related and two unrelated to the CNS;it was found that HIV did not propogate in African Green monkey kidney (Vero) cells; human cervix carcinoma (Hela) cells, and human brain astrocytoma cells. However, HIV propagated in a neuroblastoma cell line and attained peak released reverse transcriptase activity 10-14 days post-infection. HIV was also detected using antigen capture Elisa. After prolonged growth in cell culture, there were additional dramatic peaks of released RT activity. 20-fold greater than the first, and lasting from 36 to 74 days and 110 to l4ondays post- infection. The neuroblastoma cell line used is susceptible to HIV and may be useful for HIV replication and isolation studies as well as for a model related to HIV persistence in CNS cells MP9 Early and late IgM response in H_I_V infection JOEP M. LANGE*, J.V. Parry**, A. Smith***, P.P. Mortimer**, R.S. Tedder***, J. Goudsmit*, *Department of Vi- rology, University of Amsterdam, The Netherlands, **Viral Refe- rence Laboratory, Public Health Laboratory Service, London, UK, ***Middlesex Hospital Medical School, London, UK. A total of 463 sequential serum samples from 57 homosexual men, who seroconverted for HIV antibodies (Ab) in IgG ELISA and Western blot assays, were tested by solid phase IgM antibody capture as— says. The IgM responses were confirmed by immunoblot, after ab— sorption of IgG Ab, and shown to be predominantly directed to core proteins. Samples were obtained approximately every 3 months and more often in the period following IgG Ab seroconversion. The mean follow-up time was 21 months (10-25 months). In 30 people no lgM response was found. In 20 people an IgM res— ponse, not lasting longer than 3 months, was found approximately concomitant with IgG Ab seroconversion. In 2 people an IgM respon— se occurred 5-9 months after IgG Ab seroconversion and persisted thereafter. In 5 people both a transient early and persisting late (occurring 5-15 months after IgG Ab seroconversion) IgM response were found. There was no relationship between the presence of "flu—like" disease at HIV—Ab seroconversion and the occurrence of an early IgM response. In 3/7 people with a late IgM response this coin— cided with expression of HIV antigen (EIA, Abbott Laboratories) and the development of serious HIV related disease. HIV-Ag expres— sion occurred in 5/50 people without a late IgM response and serious disease developed in 2 of those. MR“) Pathologic Features of Cytomegalovirus Retinopathy Following Treatment with the Antiviral Agent Ganciclovir Jay S. Pepose*, C. Newman*, S. Koen1g**, M.C. Bach***, T.C. Quinn**, R.F. Ambinder*, et al., *The Johns Hopkins Hospital, Baltimore, MD, **National Institutes of Health, Bethesda, MD, ***Maine Medical Center, Portland, ME. We studied the eyes of 3 AIDS patients with cycomegalovirus (CMV) retinopathy who expired while receiving ganciclovir therapy. Gross, microscopic and ultra- scruccural studies of these cases revealed varying degrees of retinal scarring and active cycomegalovirus lesions at the margins of the scars. CMV antigens were localized in cells at all layers of retina at the border of the lesions and in isolated cells in a perivascular location within histologically normal appearing retina. These areas probably represent sites of recrudescence when the drug is discontinued. In siCu hybridization using a cloned cDNA probe of human CMV corroborated the immunocycologic localization of virus. Ultrastruc- tural studies revealed megalic syncytial cells containing mostly capsids exclusively in the cell nucleus. In situ hybridization using an HIV riboprobe did not detect HIV-infected retinal cells, whereas brain tissue from other cases were positive using the same probe. The cytoplasmic electron-dense membrane bound bodies that have characterized untreated cases of CMV retino- pathy were absent in the created cases. An attempt to isolate CMV in tissue culture from the vitreous and retina of one of the cases yielded a negative result. Our results indicate that ganciclovir does not effectively eliminate CMV from the retina nor does it suppress expression of all viral genes. Ganciclovir appears to function by limiting viral DNA synthesis and subsequent packaging of viral DNA into infectious units, thereby acting as a virostacic chemotherapeutic agent. MONDAY, JUNE 1 nnR11 Human immunodeficiency virus isolates differ in replication poten- tial in vitro. FRANCESCA CHIODI*, E.M. FENY6*, J. ALBERT*, B. ASJ6*. *Department of Virology, Karolinska Institute, Stockholm, Sweden. Human immunodeficiency virus (HIV) has been isolated from 33 HIV antibody positive individuals with different clinical manifestations of infection. Peri- pheral blood mononuclear cells (PBMC) from AIDS or pre—AIDS patients yielded virus rapidly as detected by high reverse transcriptase (RT) activity in cul- ture fluids. These viruses were able to establish a persistent infection in several T4 antigen positive tumor cell lines (CEM, H9 and U937 clone 2) and were designated rapid/high. PBMC cultures from individuals with mild or no symptoms yielded virus more slowly and the RT activity was low. Cocultivation of PBMC yielding such slow/low viruses with the T4 positive tumor cell lines showed no or only transient virus replication, as a rule. Cell free trans— mission of viruses to PBMC from normal donors and to cell lines showed that viruses classified as rapid/high are readily transmitted whereas viruses of the slow/low type replicate poorly, if at all. In fact, slow/low viruses could be divided into 4 groups on the basis of their transmissibility and growth properties. Viruses in group 3 and 4 could efficiently replicate in the Jurkat/tat cell line allowing radioimmunoprecipitation and restriction en— zyme analySis. M212 HIV Entry into CD4+ T Cells Occurs Via pH-lndependent Viral Envelope Fusion to the Plasma Membrane EARRV S, §TEIN, S.D. GOHDA, J.D. LIFSON, R.C. PENHALLOH, K.G. BENSCH, E.G. ENGLEMAN, Stanford University School of Medicine, Palo Alto, CA. After binding to specific cell surface receptors, enveloped RNA viruses are known to deliver their genetic information into target cells via at least two distinct mechanisms: (i) by rapid internalization of virus into acidic endosomal vesicles where envelope proteins undergo requisite low pH-dependent conformational changes which facilitate direct virus envelope fusion with endosomal membranes, or (ii) by direct fusion of virus envelope with the plasma membrane of the cell in a pH~independent fashion. CD4 is the cell surface receptor which confers HIV target cell tropism through interaction with mature envelope (gplZO); however, the mechanism whereby this enveloped RNA retrovirus enters susceptible cells is not known. In our studies neutralization of acidic endosomal and lysosomal vesicles (pH > 6.4) with various lysosomotropic agents including chloroquine, NH4Cl, and monensin, did not prevent HIV entry. Viral entry was quantitated by Slot Blot analysis of cytoplasmic HIV DNA isolated from CD4+ T cells exposed to HIV for 4 hours in either the absence or presence of lysosomotropes. Speci- ficity of the HIV DNA detected was confirmed by Southern blot which revealed a 9.7 kb hybridizable fragment in each treatment group. EM studies of VB cells acutely exposed to HIV at neutral pH revealed direct fusion of virus envelope with the plasma membrane within minutes of mixing uninfected cells with free virus at 4°C. No endocytosed virions were visualized upon rewarming the virus exposed cells to 37°C. These results indicate that HIV preferentially enters C04+ T cells via pH-independent membrane fusion rather than by a low pH«dependent endocytic route. M213 Characterization of Genetic Mutants of HIV that. are Detective in 335 Gene Processing. RAUJL E. BENVH‘IISTEI. L.J. M31, K. NAGASHDlAttt, M.A. Will. XNational Comer Institute. Frederick. MD, ”Fairfax Hospital, Falls Church, VA, *throgram Resources, Inc., Frederick, MD. An HTLV—III/LAV isolate obtained from an AIIS patient was shown to be poorly infectious for humn lymphocytes. SDS—PAGE analysis of proteins associated with this virus, designated HIV(Fre—3), showed that it cmtained largeamunts of the a; viral protein precursor, Pr55. Electron microscopy (EM) of infected Hu'l‘ 78 cells revealed two populations of virus—producing lymphocytes. (he produced virus which natured and had a normal mrphogenesis, while the other produoed only aberrant "imture" extracellular virus particles. This lymplaocyte culture was cloned on sheep choroid plexus cells and 51 single cell clones were obtained. Some of the clones produce infec- tious HIV (reverse transcriptase positive, mature m proteins visualized on SDS-PAGE) which by E1 appear manual in all stages of maturation. other single—cell clones release non-infectious. structurally aberrant viruses which contain an electron-linent core surrounded by a sanielectron—dense inoanplebe ring of ribonmleoprotein, and thus resemble iii-nature extra— cellular virus particles. These clones lack detectable announce of the mature Egg proteins and munulate large ammts of the Pr55 gag precursor; some also lack reverse transcriptase activity. Clones producing the non-infectious particles cannot be superinfected by infectious HIV. Purified and lysed whole virus preparations have been shown to lack an intact protease; the addition of protease isolated from a "wild—type" virus results in the degradation of Pr55 to intact mature 39; proteins. These results suggest that the genetic defect may be in the protease gene itself. These HIV mutants might provide a useful model for the design of protease inhibitors. 12 M214 Helix Twist Angle Analysis of Retroviral LTR Sequences C.-S. TUNG and GERALD MYERS, Theoretical Biology and Biophysics Group, Los Alamos National Laboratory, Los Alamos, NM, U.S.A. Degeneracy in the coding regions of genomic sequences can be analyzed in terms of "silent mutations" and conserved amino acid substitutions. In this study, we are exploring an analytical approach to degeneracy in non-coding DNA: the equivalent of a "silent mutation" is a base change that preserves the helix twist angle of the double-stranded DNA. A structural homology is a series of helix twist angles that are equivalent in two or more DNA sequences, irrespective of whether they happen to be sequence homologues. Genomic LTRS (long terminal repeats) found at the 5' and 3' termini of retroviruses such as the HIV group, which utilize a trans-activating mode of control of viral replication in contrast to other LTR—directed mechanisms, offer an interesting class of sequences for this study. In particular, the TAR region (trans-activating receptor or target) found downstream from the mRNA start site has been the focus of our attention. with a very stringent criterion of structural similarity, one helix twist pattern can be identified in all human and simian viral TAR sequences, repre- sented by the consensus sequence ”ctccga.” The pattern is found at the same position for the most part; however, it occurs at a different position in HTLV—I and visna virus, in the former as "ggcch" and in the latter as "ctccgg." with exception of visna virus, this pattern is found only in cer- tain non-primate viral LTRs at yet a third position, which encourages us to pursue this mode of comparative analysis. MP15 In vivo Transmission Studies with MnIV, a Primate Lentivirus Partially ' Related to HTLV-III WILLIAM R. MORTON“, M.E. THOULESS”, E.A. CLARK", H.D. ocns", R. BEN— VENISTE***, *Regional Primate Research Center, University of Washington, Seattle, WA, * Department of Pediatrics, University of Washington, “*NCI, Frederick, MD. A retrovirus has been isolated after co—cultivation of a lymph node from a pig—tailed macaque (M. nemestrina) that died with lymphoma in 1982 at the University of Washing- ton Primate Center. This isolate, designated MnIV (M. nemestrina immunodeficiency virus) is partially related to HTLV-III, based on amino acid sequence homology and immunological cross—reactivity of the major gag protein, p28. 103 infectious MnIV particles from an end—point diluted virus preparation grown on HuT 78 cells were inocu— lated i.v. into two species of macaques (rhesus — M. mulatta and pig—tailed). All macaques (six animals) became viremic and MnIV could be readily isolated from their peripheral blood lymphocytes. Two of the six macaques have died with opportunistic infections, anemia and depleted T4+ cells at 4 and 15 months after inoculation. All macaques developed high titers of antibodies to MnIV, except for the animal that died at four months. In a second experiment, eleven young cynomolgus macaques (All; fascicularis) have been inoculated i.v. with MnIV isolated directly on human lymphocytes. Six of these animals had previously received vaccinia virus containing the envelope protein of HTLV—III and had antibody titers to gp120 and gp41. These animals are being monitored to examine whether the presence of HTLV—III antibodies protects against a subsequent challenge by the related virus MnIV. MP1s HIV verification testing:A comparative study of the inmunoreacti- vity of a cloned envelope protein (go 160) and commercially avail- able viral lysate M.V. 0'SHAUGHNESSY*, M. COCHRAN**, G. SMITH**, *Laboratory Centre for Disease Contro , Uttawa, Canada, **MicroGeneSys., West Haven, Conn. In most HIV antibody detection protocols, ELISA reactivity must be verified by one of several methods including immunoblot, indirect-immunoflourescence or radio-immune precipitation. In LCDC the immunoblot has been the standard verification assay with more than 25,000 sera having been tested. Deficiencies in the inmunoblot which will be described include: the presence of contamina- ting, co-migrating cellular products (e.g. a 24k polypeptide of cellular origin), batch to batch variation in antigen quality - including the propor- tion of individual viral components and unusual patterns of antibody reacti- vity against viral specific polypeptides. The envelope gene of HIV (LAV) has been inserted into a Baculovirus and a polypeptide of about 160k expressed in insect cells. The efficacy of this bioengineered product as a diagnostic reagent has been evaluated using an immunoblot format and a spot—blot variation of it. More than 500 sera have been analyzed by both the standard immunohlot using a commercially prepared viral lysate and the alternative procedures employing the cloned gene product. Sera that react with only a p24 antigen in an immunohlot are considered HIV antibody equivocal. 12 of 30 equivocal sera reacted with the gp160 protein. All 12 were confirmed as antibody positive by RIPA and 18 were antibody negative. Similarly all of the 20 sera that reacted with only HIV qp41 also recognized the qpl60 envelope protein. Our data indicate that both the sensitivity and specificity of procedures employing the cloned gp160 exceed those of protocols which rely upon a commercially prepared viral lysate. MONDAY, JUNE 1 “"217 Neutralizing antibodies and cellular immune response in goats immunized with native envelope gp120 or with recombinant envelope proteins. *, w.G. ROBEY**. S. PUTNEYxxs, P.J. FISHINGER** R.C.GALLO* AND A. RANKI* et al, *Laboratory of Tumor Cell Biology, NCI, Bethesda, MD, *Office of the Director, FCRF, NCI, Frederick, MD, «*xRepligen Corporation, Cambridge, Mass. Goats were immunized with native gp120. purified from HTLV—IIIB infected cells or with recombinant peptides representing various parts of the HIV ENV gene and produced in E. Coli or in an insect cells. Neutralizing antibodies were looked for by assessing the ability of the sera to prevent cytolytic action of HIV on a sensitive target cell, ATH-8. Cellular immune response to HIV was studied by assessing the proliferative responses of T cells stimulated with whole heat killed HIV, purified gp120 or with the recombinant peptides. Native gp120, two nonglycosylated recombinant peptides produced in E. Coli (P31 and 5-90) and a giycosylated envelope protein produced in insect cells all elicited neutralizing antibodies. If the recombinant protein contained sequences from gp41, the neutralizing response was group specific, otherwise only type specific antibodies were seen. A group specific cellular immune response to three HIV isolates were seen in animals immunized with giycosylated native gp120 or with the recombinant glycoprotein from insect cells. The results suggest, that in spite of the great variability observed in the external envelope of HIV, vaccines representing one isolate may elicit a broad, group specific protective immune response. hflRlB Preliminary Clinical Trial of Anti—Alpha IFN in Patients with AIDS: A Possible Approach for Immune Enhancement. JOSEPH A. EELIANEI*, SIMON V. SKURKDVICH**, STEPHEN M. PETERS*, SUMIT JOHL*, NEZIH CEREB*, AARON J. HSU“. *Georgetown University School of Medicine, Washington, D.C. and **ABC, Inc., Columbia, MD. Based upon the hypothesis that acid—labile alpha IFN may down-regulate the immune system (Skurkovich, S.V., Skurkovich, B. and Bellanti, J.A., Clin. Immunol. Immunopath., 1987, in press), a study was performed to evaluate the safety and clinical efficacy of anti-alpha IFN in patients with AIDS. Two pa— tients with CDC—defined AIDS who had recovered from 3. car i pneumonia, re— ceived three daily intramuscular injections of sheep anti-alpha IFN immunoglob- ulin (1.5 to 9 x 106 I.U./day respectively) for a 6-day period during which time and subsequently thereafter (3 months and 3 weeks, respectively), clinical and laboratory parameters were evaluated. Although no serious adverse or toxic effects were observed following treatment, both experienced a mild maculopapu— lar exanthem on the 9th to 10th day which disappeared within a week. In both patients on the 3rd day a mild transient lymphopenia was observed which disap— peared by the 6th day. Following treatment both patients had a sense of well being; patient #1 experienced an 8 lb weight gain within 14 days of treatment. Before treatment both patients had detectable serum levels of acid labile alpha IFN (125 IU/ml). During the 6—day treatment period no IFN could be detected in the blood of either patient. However, 7 days after the cessation of treatment serum IFN levels in patient #1 increased to 630 IU/ml which was predominantly gamma IFN. Although the results thus far are promising and suggest the approach is feasible with negligible side effects, the long term efficicacy of anti—alpha IFN in AIDS will require further studies of dosage and frequency of administration. M219 Herpesviral Transactivation of the Human Immunodeficiency Virus (HIV) Long Terminal Repeat Sequence. HOWARD E. GENDELMAN*, JOHN LEONARD*, KAREN WECK*, ARNOLD B. RABSON*, DANIEL CAP0N**, MALCOLM A. MARTIN*, JEFFREY M. OSTROVE***. 'Laboratory of Molecular MicrobiolOgy, and ***Laboratory of Clinical Investigation, NIAID, NIH, 9000 Rockville Pike, Bethesda, MD 20892; **Genotech, Inc., South San Francisco, CA. During the course of infection with HIV many individuals became coinfected with a variety of microorganisms. Since some of these pathogens may act as cofactors capable of stimulating HIV expression and thus accelerate disease, we examined one common coinfecting pathogen, herpesvirus type-I (HSV—l), for its ability to increase HIV gene expression. when an HIV LTR clone linked to the indicator gene chloramphenicol acetyl transferase (CAT) was transfected into Vero or SW480 cells, then infected with HSV-l, a 25-fold stimulation of CAT activity was observed. This effect was further increased by transfection of HIV Eat DNA into cells subsequently infected with HSV-l. In cotransfection experiments of HIV LTR—CAT or an infectious molecular clone of HIV and recombinant plasmids containing three HSV-l immediate early genes, segments encoding ICPO and ICP4 stimulated CAT expression or reverse transcriptase activity while ICP27 had no effect. Analysis of HIV LTR deletion mutations revealed that the target of the HSV-l encoded products was distinct from that responsive to the HIV tat gene. Primer extension experiments demon- strated a transcription component to the HSV—l transactivation. 13 MPZO Membrane Fusion Activity and Entry of HIV-1 MVRA 0. McCLURE*, M. MARSH*, A.G. DALGLEISH*, R.A. NEISS*, *Chester Beatty Laboratories, Institute of Cancer Research, London. Internalisation of enveloped viruses into cells proceeds by one of two mechanisms. Some viruses (e.g. Sendai) fuse with target cell plasma membranes in a pH-independent manner. For others, however, (e.g. influenza, VSV), the fusion is pH-dependent. In these cases virions are internalised by receptor- mediated endocytosis and fuse with endocytic vesicles (endosomes) to release the nucleocapsid into the cytoplasm. The low pH triggers a conformational change in the viral spike glycoprotein which renders them fusogenic. We have ascertained whether HIV-1 follows either of these mechanisms of entry. Weak bases (e.g. amantadine, NH4Cl) and carboxylic ionophores (e.g. monensin), which have been shown to inhibit the entry of pH-dependent viruses do not inhibit HIV-1 entry into CD4+ C8166 cells. Prolonged incubation in NH4Cl does, however, reversibly inhibit the production of infected virus, both in C8166 cells and in chronically infected H9 cells. Furthermore, the entry of VSV (HIV-1) pseudotypes is not inhibited by NH4Cl, even though non- pseudotype VSV is inhibited. These data suggest that HIV-1 induced membrane fusion is not dependent on low pH but that weak bases affect the maturation of virions. Immuno-electron microscopy for the CD4 antigen on C8166 cells indicates, however, that receptor-mediated endocytosis may be a method of internalisation of the virion-complex. MP21 A Simple Method for Detecting HIV-Antibodies Hidden in ' Circulating Immune Comp exes +* + + SUSAN R.HDLLAN ,G.FUST , B. BUKI ,A.HDRVATH ,E.UJHELYI ,G.KRALL + Natl.lnst.Haematol.Blood Transfusion,++Natl.Inst.Dermatol. Venerol.,Budapest,HUNGARY In early and late (AIDS) stage of HIV infection ratio of HIV— antibodies to antigens may be near to equivalence with no free antibodies in blood. In these periods negative or doubtful reac- tion can be expected in anti-HIV assays.We have worked out a method for detecting HIV—antibodies hidden in immune complexes. Immune complex—enriched fractions were prepared from the sera tested by PEG precipitation.F(ab')2 fragments were released from complexed antibodies by low pH pepsin treatment.HIV antibody activity of the F(ab')2 fragments was compared to that of the original PEG precipitates using plates of Vironostika anti- HTLV—III kits as solid phase antigen. Antibodies fixed to the plates were detected either directly by a peroxidase-labelled anti-human KuL—antibody or by a competitive assay, measuring the fixation of HIV—antibodies to plates pretreated by F(ab‘)2 or PEG precipitate. Using both methods significantly higher antibody activity was found in F(ab')2 fragments than in the original PEG precipitates in 9/10 sera of confirmed anti-HIV positive patients.lherefore, our method seems to be suitable for detecting HIV—antibodies hidden in immune complexes. MPZZ Regulation of HIV Long Terminal Repeat (LTR) Activity. ' K. WECK‘, K. CLOUSE****, H.E. GENDELMAN‘, J. OSTROVE**‘, T. F0LKS**, and A.B. RAasou*. *LMM, **LIR, & ***Lc1; NIAID; NIH; Bethesda, MD 20892; and ****Georgetown University, Washington, DC. The HIV LTR contains regulatory sequences that modulate viral gene expression. In order to delineate the sequences responsive to the viral £32 protein, a series of mutations in the LTR tar region have been constructed employing deletion mutations and synthetic oligonucleotides. when tested for their ability to drive the expression of the chloramphenicol acetyl transferase (CAT) gene in the presence of tag, it was observed that LTR sequences lying between +37 and +62 were required for tag responsiveness. Additional mutations in the Egg region are currently being studied both by CAT assays and in recon— structed viral genomes. Expression of the HIV genome may also be regulated by cellular transcription— al factors. We have been studying the activation of HIV expression in U1 cells, a cloned macrophage cell line containing integrated proviral DNA and expressing low levels of viral RNA. when Ul cells are treated with the super- natant from lipopolysaccharide (LPS)- induced macrophages, viral RNA levels increase approximately 40-fold. Thus, stimulated macrophages may produce factors that transcriptionally activate quiescent HIV proviruses, presumably by altering the cellular transcriptional milieu of latently infected cells. The ability of purified monokines to augment HIV transcription in infected cells is being studied and the location of LTR sequences required for this activation is being analyzed employing HIV LTR segments mutated in the £35 region and in upstream regulatory elements. MONDAY, JUNE 1 M223 structure/Function studies of Cloned HTLV-III/LAV from Zairian and French Individuals JOSEPH YOURNO,* S. F. JOSEPHSI *A. G. FISHER,* D. ZAGURY,‘* F. WONG-STAAL,* and R. c. GALLO,’ *Laboratory of Tumor Cell Biology, National Cancer Institute, NIH, Bethesda, MD, "*Universite Pierre et Marie Curie, Paris, France. Different isolates of HTLV-III/HIV, the etiological agent of AIDS have extensive genomic diversity in nucleotide sequence with greatest divergence centered in the en! regions and the most conserved regions in the gag and pol genes. Mechanisms which generate such diversity may allow the virusnto survive host immune surveillance. Consistent with this, variants have been selected for when the virus is grown in vitro in the presence of neutralizing antibodies. To better understand the genetic divergence responsible for this phenomenon and to prepare additional reagents which may be useful for vaccine development it is necessary to study a large number of HTLV—III/HIV isolates. We have isolated and cloned viruses from two individuals with AIDS, one from Zaire (JY—l) and one from France (JV-2). The clones were obtained by isolating 9 Kb HWLV-III SstI fragments stretching from the 5' leader to the 3' LTR from phage lambda libraries. Comparison of the restriction enzyme maps of JY-l and JY—Z and a prototype earlier American isolate, BHlO, show that the 5' gag and pol regions share 10 of 12 sites while the 3' portion is less well conserved with 7 of 11 sites in JY—l and 7 of 11 for JY—2. JY—l appears to be more closely related to the American isolate than previously described zairian isolates (Benn et al., Science 2&2, 949). substitution of the protein coding regions of these viruses into the biologically active clone pHXBZ-d yielded clones which produced virus after transfection into Cos—l cells. Nucleotide sequencing is in progress. MR24 Suppression of AIDS Virus Replication _i_n vivo by D-Penicillamine + P. Sarin*, Daisy Sun‘, M. Civeira*, R. Schulof, Allan Goldstein , P. Chandra . Laboratory of Tumor Cell Biology, National Cancgr Institute,* Bethesda, MD, George Washingtgg, University School of Medicine , Washington, D.C., University of Frankfurt , West Germany D—penicillamine (DPA) has been shown to inhibit HIV (HTLV-lIl/LAV) repli— cation in-vitro (Chandra and Sarin, Drug Res. 36: l, 184, 1986). It was therefore of interest to assess the in-vivo activity of DPA on virus repli- cation in HTLV-III-infected patients with generalized lymphadenopathy (LAS) or ARC. Patients were treated on a high-dose regimen (0.59 escalating to 29), or a low-dose schedule (0.59 daily) for 2 weeks to 4 months. A suppression of virus replication was observed in all cases, however the intensity of this inhibition was dependent on the dose schedule and the duration of treatment. In patients treated at low dose, the inhibitory response was in the range of 30-50%. which was reversed after two weeks of treatment termination. Three of five patients treated at high dose showed a complete inhibition of viral repli- cation, and this suppression of HTLV-III replication persisted up to 24 weeks after the treatment was stopped. MP25 Nucleotide Sequence of an Active m cDNA Clone of Simian T-Lympho- tropic Virus Type III SANDRA COLOMBINI * S. ARVA,* L. JAGODZINSKI,** M. S. REITZ,* B. BEAVERS,* R.C. GALLD,* and F. H6NG-STAAL,* *Laboratory of Tumor Cell Biology. National Cancer Institute, NIH, Bethesda, MD, **Biotech Research Laboratory, Inc., 3 Taft Court, Rockville, MD. The human T-lymphotropic viruses shared, among other common properties, the ability to regulate their own expression mediated by transacting viral regula- tory proteins. The prototype AIDS virus, HTLV-lII/HIV, has at least three pos- itive transactivating genes (Sgt-III, £5; and §9:) operating at various stages of virus expression. Recently, a second subgroup of primate retroviruses related to HTLV-III/HIV has been identified. The prototype of this subgroup is the simian T-lymphotropic virus type III (STLV-III GM) isolated by Kanki et al., from African green monkeys. In order to understand the transregulatory function of this new virus subgroup, we cloned and sequenced a functional transactivating cDNA from STLV-III. The complete cDNA clone is 2049 nucleo- tides in size. It comprises 4 exons and three open reading frames. These are analogous in position and size to the £31, tr; and 3'-9§f genes of HTLV—III. Alignment of the putative STLV-III tgt gene with EEE'3 revealed a highly con- served core sequence which likely represents the functional domain. We assayed the transactivating capacity of our cDNA clones by co-transfection with a plasmid pSVZCAT containing the putative transactivation target sequences (TAR) of the STLV-III LTR upstream of CAT. It showed marked transactivating function and this function is maintained when we substituted pSVZ CAT with the corres— ponding construct with HTLV-III LTR. We conclude that this new subgroup of primate retroviruses are similar to the HTLV-III/HIV viruses in their genomic organization and strategy for gene regulation. 14 M226 Transactivatlon of Human Immunodeficiency Virus by Herpesviruses C. BOHAN*, P. LUCIW**, P. PELLET*, A. SRINIVASAN*, *Centers for Disease Control, Atlanta, GA., **University of California, Davis, CA. We examined the interaction of human immunodeficiency virus (HIV) and herpes group viruses. For this purpose, a chimeric plasmid (pLTR-CAT) was constructed in which the long terminal repeat (LTR) sequences derived from a molecular clone of HIV were fused to a bacterial chlorsmphenicol acetyltrsnsferase gene (CAT). Transient expression assays in transfected tissue culture cells were used to monitor the activity of the LTR. Basal levels of CAT activity were measured in HeLa and human lung fibroblast (HLF) cells transfected with pLTR-CAT. when HeLa or HLF cells transfected with pLTR CAT were infected with herpesviruses, HIV-LTR directed expression of the CAT gene was detected. Activation of HIV-LTR directed expression of CAT was observed for herpes simplex viruses (HSV-l and usv—z), cytomegslovirus and varicella zoster virus. Activation of CAT expression directed by the LTR was observed by cotrsnsfection of subgenomic fragments derived from HSV-l, HSV-Z, and CMV genomes. We have also constructed a series of recombinant plasmids containing deletions and multiple point mutations in the HIV-LTR sequences linked to the CAT gene. HeLa cells were transfected with such plasmids and followed by superinfection with herpesviruses to identify the sequences required for transactivation by herpesviruses. HIV-LTR directed expression may be a useful model for studying the effects on HIV of various infectious agents known to be present in individuals with AIDS or HIV infection. MB21 SIV/Sim: Prevalence and Association with Disease in a Breeding Colony of Mangabey Monkeys. HAROLD M. MCCLURE*, D.C. ANDERSON*, W.M. SWITZER**, E.A. STROBERT*, J.L. ORKIN* AND P.N. FULTZ**, *Yerkes Primate Research Center, Emory University, Atlanta, GA, **AIDS Program, Centers for Disease Control, Atlanta, GA. A colony of mangabey monkeys at the Yerkes Center has a high incidence of in- fection with SIV/SMM, a T—lymphotropic retrovirus that is morphologically iden- tical and serologically related to HIV. This colony, established in 1969 with wildborn mangabeys, currently consists primarily of lab-born animals. There has been no difference in the incidence of disease in the mangabeys as compared to other species at Yerkes. Twenty-six of 76 deaths (34%) were due to clinical diseases, including enterocolitis, pneumonia, amyloidosis, septicemia and meningitis. Candidiasis, lymphadenopathy and splenomegaly were rarely encoun- tered. Two neonates were found to have a herpetic (CMV) glomerulitis. Two re— cently encountered diseases in mangabeys, amebiasis and necrotizing gingivitis (noma), suggest that the virus infection may be associated with clinical disease and death. Amebiasis occurred in an 11-year-old female; noma occurred in a 5-month-old infant. Both animals were seropositive for SIV/SMM and virus was isolated from blood and multiple tissues from both cases, including the brain from the name case. Although 88% of the adult mangabeys checked have been virus positive, this is the first virus isolation from an infant. The high infection rate in mature animals and occurrence of infection in an infant suggests that transmission of SIV/SMM may be comparable to the transmission of HIV (sexually or perinatally). This colony of naturally infected mangabeys may, therefore, serve as a model system for study of the epidemiology and pathogenesis of an HIV-like retrovirus, and for identification of cofactors that may be associated with the occurrence of AIDS (supported by NIH grant no. RR-00165). Polypeptides of determined by MP28 Structural Relationship between Core ' Human and Simian Immunodeficiency Viruses as Peptide Mapping ELKE JURKIEWICZ*, J. SCHNEIDER*, M. HAYAMI**, V. DHTA**, H. SCHMITZ***,C. HUNSMANN*, *German Primate Centre, Cottlngen, FRG, **The Institute of Medical Science, University of Tokyo, JapanY ***Bernhard-Nocht—Institut, Hamburg, FRG. Simian immunodefiCiency viruses (SIVs) are serologically and biochemically related to the human immunodeficiency virus type 1 (HIV-1) the cause of AIDS. The SIVs isolated from macaques (SIVmac) and sooty mangabey (SIVsm) induce an AIDS-like disease in rhesus monkeys. Recently, two novel human retroviruses, HIV—2 and HTLV-IV, were found in West Africa. They are antigenically more related to SIV than to HIV-l. In order to c19551fy HIV and SIV isolates, we have compared tryptic peptide maps of the core polypeptides p18 and p24 of HIV-2, three HIV-1 and five SIV isolates. Peptide maps of all isolates are distinguishable. Differences appear to be most prominent between the two groups of HIV-l isolates and SIVmac/SIVsm. HIV-2 IS very similar to SIVmac and SIVsm. SIVs of African green monkeys (SIVagms) are the most heterogeneous group. The core polypeptides of one SIVagm isolate is more related to HIV—l. The two other SIVagms also resemble more to HIV-l with respect to their p245, but their plBs are more similar to those of SIVmac /SIVsm/HIV-2 than to those of HIV- 1. Therefore, two SlVagm isolates could be gag gene recombinants between human and simian viruses or their ancestors. MONDAY, JUNE 1 MRZQ Biochemical Features of the 3'orf Gene Product of HTLv-III/HIV JONATHAN S. ALLAN, M.F. MCLANE, P.J. KANKI, M. ESSEX, Harvard School of Public Health, Eoston, MA. He previously identified a 27kd protein (p27) from an HTLV-IIIb infected cell line which was immunoreactive with antibodies from infected people and encoded by the 3'orf gene by amino acid sequence analysis. We have extended our studies to earn more of the biochenical character- istics of p27 in the hope of gaining some insights into the functional aspects of the 3'orf gene. Initially, levels of expression of p27 were evaluated among different HTLV-III/HIV isolates and those of STLV-III and HTLV-IV using radioimmunoprecipitation (RIP) techniques. It was found that multiple species of p27 exist in some cell lines which range in molecular weight from 26kd to 30kd. Additionally, p27 is modified by fatty acid myristylation as detected by 3[Hlmyristate incorporation and a similar species (p33) was found to exist in STLV-III and HTLV-IV infected cells indicative of a conserved 3'orf gene product. P27 was shown to be cell-associated and cerulenin, an inhibitor of lipid metabolism, was found to alter the migration of p27 by SDS-PAGE suggesting that this species represents the nascent polypeptide. Although greater than 20% amino acid variability in the 3'orf gene is seen between some isolates, highly conserved regions exist and from a search of gene bank sequences we observed limited amino acid homology with EIB, an early adenovirus gene involved in tumorigenesis. These homologous sequences were confined to the conserved regions between HTLV-III/HIV isolates suggesting either structural or functional constraints in the evolution of the 3'orf gene. Mesa Expression of Large Amounts of Native and Mutated Forms of the HIV Envelope Proteins Using a SV40 Late Replacement Vector DAVID REKOSH*, A. NYGREN***, E. LINDSTROM***, H. WIGZELL*** and M-L RAMMARSKJOLD**, *Departments of Biochemistry and **Microbiology, SUNY at Buffalo, N.Y. and ***Department of Immunology, Karolinska Institute, Stockholm, Sweden. An eukaryotic expression vector producing large amounts of the HIV envelope proteins (gp 160/120) has been constructed by introducing the Sal l/Xho I fragment from the BRIO isolate into a SV40 late replacement vector. The vector is a shuttle vector that replicates to high copy numbers in both E. coli and eukaryotic cells permissive for SVAO replication. Transfection of the HIV recombinant into CV1 monkey cells gave high levels of expression of gp 160 and gp 120 in approximately 302 of the transfected cells. By several criteria the proteins were indistinguishable from those produced during infection. The proteins were localized to both the cytoplasm and the plasma membrane and some of the gp 120 was shed into the culture me ium. Approximately 0.5 ug of envelope protein could be extracted from 10 cells. Thus this transient vector system provides an abundant source of native envelope protein for purification and characterization. In addition several recombinants designed to express mutated forms of the envelope proteins have been created. MR31 Simple, Rapid, Ouantal, Syncytium—Forming Micro—Assay for the Detection of Neutralizing Antibody Against Infectious HTLV~IIl/LAV. gigggggmganp, w.c. HATCH", N. DUNLOP“, w.<;. ROHEY“, AND P.J. FISCRINGER‘, ‘Office of the Director, Virus Control Unit, NCI-Frederick Cancer Research Facility (FCRF), **Program Resources, Inc., NCl—FCRF, Frederick, MD 2170L A need for a simple, rapid, quantal cell system for the sensitive detection of neutralizing antibodies and evaluation of various antiviral agents against HTLV-III/LAV is well recognized. Herein is described a syncytial —forming assay that directly correlates with more commlicated and cumbersome infectious virus assays. A syncytial sensitive clone of CEM cells was identified and made adherent to flat bottom 96—well microtiter plates. These cells exhibit one- hit kinetic syncytium formation at a multiplicity of infection of 0.005. These syncytium develop by 5 days on a confluent cell monolayer background and remain attached for easy quantitation. These syncytial fact are associated with complete virion production and focally positive p24 immunofluorescence. Five different HTLV—III/LAV isolates (IIIb, LAV, MN, RFII, and Rut-Z, includ— ing Illb reisolated from persistently infected chimpanzees, produce quantifi— able syncytium, which varied slightly in their morphology of formation. Various antiuHTLV~IIl/LAV sera from various species (man, chimpanzee, goat, equine, and rhesus) have been tested and found to contain titers comparable to immunofluorescent methods. Infectious virus can be accurately and rapidly titered in this assay and correlated to p24 and gplZO when microtiter well supernates are evaluated by competitive radioimmunoassay methods. This assay has the advantage of allowing numerous, small volume samples of either anti~ viral or suspect antisera to be tested in a rapid and sensitive fashion. Inherent with this system is a flexible method for studying various kinetics of antibody/viral interactions, blocking, and various interference studies. Research sponsored, in part, by NCI, DRRS, under Contract NOI—CO-23910, PRL 15 M232 SHUJI NAKAMURA*, B. ENSOLI*, z. SALAHUDDIN* and R. GALLO*. * National Cancer lnsfifute, Bethesda, ND. Epidemic HTLv-III related KS is an aggressive disease of young people and is a multifocal and histologically complex lesion consisting of spindle cells, endothelial cells and fibroblasts. So far, its origin and pathogenesis remain unknown. Here, growth of KS cells were compared to normal endothelial (NE% and fibroblast like (NF) cells. Cell growth was assessed by cell number, H thymidine uptake and mitotic index. Conditioned medium from HTLV—lI-trans- formed human T cell lines (HTLV-II—CM) stimulated the growth of 6 of 6 KS cells as well as NE cells, but was much more potent for the growth of the KS cells. These KS cells, although slow growing, have been cultured with the help of this factor(s) for over 9 months, and large quantities of cells have been harvested for study. Nine well known growth factors, including endothelial cell growth supple- ment (ECGS), basic fibroblast growth factor (FGF) and IL-1, were also tested for their growth promoting effects. ECGS and FGF induced the growth of NE and NF cells, but, they had little or no effect on the growth of KS cells. Con- versely, IL-l stimulated the growth of KS cells, although it plateaued early as compared to HTLV-II-CM and had little or no effect on NE and NF cells.In addition, molecular analysis revealed that the factor in HTLV-II-CM differed from ECGS and FGF, but whether it differes from other known lymphokines, in— cluding IL-1, is under investigation. In summary, we have developed an in vitro system for the study of KS. Our results show that KS cells have 5"” different growth factor dependency than NE and NF cells. This system should provide further clues to our understanding of pathogenesis of KS. In vitro produced factors promote the growth of Kaposi's sarcoma e MP33 Comparative Structural Analysis of the M Genes of Group B T- ' lymphotropic Retroviruses (STLV—III and HTLv-III) Marvin S. Reitz, Jr., C. Gurgo, G. Franchini, E. Collalti, H.-G. Guo, F. Nong— Staal, R. Gallo, Laboratory of Tumor Cell Biology, National Institutes of Health, Bethesda, MD 20892 Recently viruses have been identified in monkeys in Africa which by serology are related to HTLV-III. They have been designated simian T—lymphotropic viruses. type III (STLV-III), and appear to cause an AIDS—like disease in macaques. Viruses related to STLV-III have been identified in healthy and apparently immunocompromised humans from West Africa. In order to compare STLV-III and HTLV-III and to try to identify common structural features which might explain their similar pathobiology, We determined the complete nucleo- tide sequence of the gny gene of STLV—III. The overall nucleotide sequence homology to HTLV-III is 52%. The homology of the inferred amino acid sequence of the efly protein to that of HTLV-IlI was 34%, substantially greater than to those of the lentiviruses visna (15%) and equine infectious anemia virus (14%). The small transmembrane en! proteins were more closely related (40%) than were the external large envelope proteins (30%). Regions of homology between these gfly gene products tended to cluster within regions which are relatively strongly conserved among different HTLV-III isolates. This suggests that these code for genetic determinants which are of functional importance to parts of the viral life cycle, such as binding to the T4 receptor protein. In addition, there is a remarkable conservation of cysteine residues (2 out of 23 cysteine residues in the HTLV—III gfly proteins are also present in that of STLV-III). This strongly suggests that they play a critical role in estab- lishing or maintaining the proper conformation of the viral envelope. Other aspects of this work will be discussed. M234 HTLV—II in Patients with AIDS and Lymphoproliferative Diseases: Isolation and Characterization. S.Z. SALAHUDDIN', C. GURGO', P.D. HARKHAM", F. JENSEN"', R. FORD**', and R.C. GALLO‘, *NIH, National Cancer Institute, Bethesda, MD, "Cytotech, San Diego, CA, "*Texas Medical center, TX. HTLV—II was previously isolated from two patients with variants of hairy- cell leukemia (1,2) and one hemophilia patient with AIDS (3). However, recently serological (4) studies indicated that HTLv-II might be more widely disseminated. During the process of screening patients for antibody to HTLv—I/II and HTLv-III, several with diseases not previously associated with HTLV-I infection were found seropositive for HTLV-I/II. A retrovirus was isolated from peripheral blood or lymph node leukocytes of six of these selected patients which, upon further characterization, proved to be HTLv-II. Two patients with a history of intravenous drug abuse, diagnosed with dermato— pathic lymphadenopathy, had concomitant infection by HTLv—II and HTLv-III. HTLv-II was also isolated from one patient with prolymphocytic leukemia and from three patients with hairy-cell leukemia. These and previous observations demonstrate that in addition to its' association with, at least, some variants of hairy-cell leukemia, HTLV>II is more widely disseminated and possibly associated with other malignancies. l. Kalyanaraman, SE El., Science 2i£z571, 1982. 2. Rosenblatt, gg 31., N. Engl. J. Med., 315:372, 1986. 3. Kalyanaraman, st 33., anao J., 4:1455,'T?85. 4. Robert-Guroff, gt 23., J. Am. MEa. Assoc., 33;:3133, 1986. MONDAY, JUNE 1 M235 Analysis of Sera Exhibiting Atypical Reactions With HIV KATHLEEN SHRIVER, J. KLANIEKI, R. HOUGHTON, R. MASINOVSKY, J. McCLURE and A.J. WATSON, Genetic Systems Corporation, Seattle, WA, USA During clinical trials of a screening assay for antibody to HIV (Genetic Systems LAV EIA), a small number of atypical sera (n=6) were identified which were positive by EIA, negative by radioimmunoprecipitation (RIP), and positive only with single core antigens p25 or p18 (with or without precursors p55 and p40) by Western blot. A study was initiated to collect and charact- erize a larger sample group in order to assess the significance of this reactivity. In total, 91 atypical samples were analyzed. Twenty—five samples reacted with p25, 42 with p18, 19 with p18 and p24, 4 with p25 and p34 and one with p18 and p34. In nine individuals where sequential samples were avail— able, no significant changes in serum reactivity were observed over 6 mos. to 2 yrs., arguing that these samples do not represent seroconversions. Viral cultures attempted from cells of nine individuals were negative when analyzed by fluorescence, RT assays and antigen capture. Futhermore, no reactivity to STLV-III, HTLV-I, or LAV—II viral antigens was found in 26 samples tested. These results suggest that Western blot reactivity with core antigens alone, in the absence of RIP reactivity, does not indicate prior exposure to HIV. Atypical sera were further analyzed using a prototype second generation ELISA which incorporated synthetic peptide antigens containing sequences from ENV, (gp41), GAG (p25) and POL (p34). Only 5.5% (5/91) of atypical sera reacted in this assay, whereas a similar assay using E. coli recombinant p25 and p18 antigens detected 61% (16/26) of atypical sera. Immunoassays based on peptides may therefore offer the opportunity to significantly reduce false positives attributable to the reactivity of atypical sera. MR36 Analysis of the Reactivity of Human Sera to a HIV m Region Capable of Eliciting Neutralizing Antibodies in Animals Using Synthetic Peptides M.-C. GANFIELD. D.M. WASELEFSKY. W.R. KENEALY. D.L. REED. T. . MATTHEWS*. S.R. PE'I'I'EWAY. E.I. du Pont de Nemours, Medical Products Department. Wilmington. DE. and *Duke University Medical School, Durham. NC. Recent studies indicate that portions of the HIV m open reading frame encode protein sequences which can elicit neutralizing antibodies in goats. We have analyzed the reactivity of HIV positive human sera to these regions using overlapping synthetic peptides. A rapid peptide synthesis method was used to make overlapping peptides covering the entire gp120 region. Peptides of 15 to l6 amino acids with 5 overlapping amino acids on each end were made. Seventeen peptides. covering a region of [MB previously shown to elicit neutralizing antibodies in animals (PvuIl-Bglll). and thirteen peptides covering the same region of an envelope variant strain RF. which had sequences different than ”[3. were tested. Peptides were immobilized on ELISA plates directly by glutaradehyde and analyzed using normal and HIV ELISA positive sera. Three peptides from IIIB reacted strongly with 30-40% of the HIV ELISA positives. Selected sera were fractionated on affinity columns made of reactive peptides and the activity of eluted antibodies was assessed. In addition peptide conjugates were injected into guinea pigs: and the ability of anti-peptide antibodies to react with viral proteins and/or inhibit infectivity was tested. The results of these experiments will be discussed. M237 HIV Related Sequences in Insects from Central Africa JEAN-CLAUDE CHERMANN*, J.L. BECKER*, U. HAZAN*, B. SPIRE*, F. BARRE- SINOUSSI*, . et a ., * Institut Pasteur, Viral Oncology Unit, Paris, France, ** Institut Pasteur, Bangui, République Centrafricaine. We have studied the presence of HIV related sequences in more than 200 in- sects from endemic area for AIDS in Central Africa. This analysis has been per- formed using squash blot, dot blot and southern blot techniques. Viral sequen- ces have been found among insects from urban or suburban area, directly or in- directly in contact with humans. Positive insects included mosquitoes. antlions tsé-tsé flies, cockroaches, ticks and bed-bugs. Squash blot analysis indicated that up to 30 % of mosquitoes from endemic area contained such viral sequences. Studies on mosquitoes also suggested a transovarian transmission of the viral genes since positive results were observed both with males and females. Insects with specialized feeding such as termites or crickets were constantly found negative. Flies, bees. day-flies from Paris area were also negative. The spe— cificity of the hybridization signals has been confirmed using several probes as negative controls. Such controls included hybridization with pUClB, Kappa globulin, HILVl, type D SRV and M-MuLV probes. Hybridization with subgenomic HIVl probes also indicated that most of the viral genes are present in positive insects. However the restriction patterns observed by southern blot analysis is not similar to the one obtained with the prototype HIVt strain. These re- sults suggest that insects might be contaminated by infected human material and thus could be carriers of HIV genes but not vectors as clearly evidenced by previous epidemiological studies. ___ 16 M238 Cerebrospinsl Fluid (CSF) Studies in Adult and Pediatric HIV Infections CECELIA HUTTO, G.B. SCOTT, E.S. PARKS. M. FISCHL, H.P. PARKS, Departments of ediatrics and Medicine, University of Miami School of Medicine, Miami, FL Studies of cerebrospinal fluid (CSF) in virus—positive adult and pediatric patients were compared. The groups included 11 adults (20 specimens) enrolled in a trial evaluating 3'-Azido—3'-deoxythymidine (AZT) and placebo and 14 children (19 specimens) with HIV infections in whom lumbar punctures were done because of fever and possible sepsis. Sequential isolation attempts from CSF were made from 2 children and 7 adults. All patients were repeatedly virus-positive from peripheral blood leukocytes and all had HIV-associated clinical disease. All children had delay in growth and/or developmental milestones and 2 had progressive neurological dnene.HIV was recovered from the CSF of only 4/14 <29m children. Neither of the children with progressive neurological disease was CSF virus—positive. CSF cell count and protein were normal in 3/4 children with positive and 7/10 children with negative cultures. CSF cultures for HIV were positive in 8/11 (731) adults including 3 patients on multiple occasions. Although the CSF cell count was abnormal more often in virus- positive (1002) than virus-negative CSF (46%), cell counts even 'n virus positive CSF were only slightly elevated (mean — 9 lymphocytes/ mm L There was no significant difference in the proportion of virus—positive and virus-negative CSF with elevated protein. 622 (mean 57 mg/dl) and 502 (mean 52 mg/dl), respectively. Patients with Virus-positive CSF culture only became negative in patients receiving AZT (2/4). HIV is more readily recovered from the CSF of HIV-infected adults than children even if neurological abnormalities are present in the pediatric patients. The usual parameters of inflammation. elevated cell counts and protein. apparently are not predictive of the presence of virus MR39 and CD4: Binding Region in GP 120 and Role of Carbohydrates. Interaction between GP 120, the Major Env Protein of HIV, ANDERS NYGREN*, P.FLODBY*; T. BERGMAN**, K. LUNDIN*, H. J5RNVALL** , H. WIGZELL*.,*Dept of Immunologi, Karolinska Institute,Stockholm, Sweden. ** Dept of Physiological Chemistry,Karolinska Institute, Stockholm, Sweden. The interisolate variation of the env region of HIV is one of the major problems for the production of an AIDS vaccine. In order to find a conserved CD4-binding region in GP 120 we have performed enzymatic digestion of this protein for subsequent testing in a simple binding assay developed in our laboratory. Two fragments were found to bind to the CD4 receptor. Preliminary analysis of these fragments indicates that the bindingsite in GP 120 is located in the carboxyterminal region. Deglycosylated GP 120 (DC 120,MN 58- 60) has been shown to bind to the CD 4 receptor with much less avidity than GP 120 in its native form. Further studies including kinetics of the deglycosylation of GP 120 were carried out and revealed a significantly different efficacy depending on the enzyme used. DC 120 was tested in our bin- ding assay. Our conclusion is that carbohydrates stabilize the peptide con- figuration necessary for CD 4 binding to occur. ME40 Experimental assessment of bedbugs and mosquitoes as vectors of Human Immunodeficiency Virus (HIV) PETER G. JUPP and SUSAN F. LYONS, Department of Virology, University of the Witwatersrand and National Institute for Virology, Johannesburg, South Africa. In vitro experiments were conducted to assess whether the common bedbug (Cimex lectularius), the tropical bedbug (Cimex hemipterus) and the mosquito (Aedes aegypti) could act as vectors of HIV. The insects engorged through a membrane on a blood—virus mixture. At various intervals after feeding insects were killed, stored at -70°C and subsequently tested in pools of S for reverse transcriptase activity. This was done by inoculating each insect extract into H9 lymphocyte cultures, passaging the cells for 3-6 weeks and then testing culture supernatants for reverse transcriptase activity. HIV was thus shown to survive in Q. lectularius for up to 4 hours, in Q. hemipterus up to 1 hour but to remain undetectable in Ag. aegypt . Four attempts to transmit HIV by interrupted feeding, using groups of 100 g. lectularius, from a blood—virus mixture to uninfected blood failed. It is concluded that Ag. aegypti and probably other mosquitoes are not vectors of HIV. The results also tend to discount transmission by bedbugs. However, the survival of virus in bedbugs, especially in g. lectularius, would permit the bugs to transmit HIV mechanically between humans under natural conditions provided interrupted feeding were to occur and the virus was sufficiently infectious. Whether the former occurs is unknown but HIV is known to have a low infectivity. MONDAY, JUNE 1 M241 fl Infectim in Drug Addicts : an Epidaniological sum in Turin, Norm may. IVAN) DAL ME“, A. W“, S. (XDLCMBO‘, G. GIULIANI“, E. NIGRA“, R. DIE‘CDJJE', *U.S.L. 1% TORI“) Pss.San.Basc~Sen/izio Tossioodipenda'ize, Area di Epidemiologia, Lamratorio di Vixologia, Torino, Italy, WUl'lfivei’sit'é degli Studi—Istimto Walattie Infettive, Torino, Italy. IleBSwem‘derbookasm/eytoestinabemeprevala'iceofminfectimandtheriskfactorsas sociated with seropositivity in dag addicts (DA) attending the N.H.S. Centers, Turin. All 320 subjects enrolled were IV henoin dubxns on difflaxxm treabnsns. Mean age was 26.4 (S.D. 4.56). 78% "ales and 226 fenales. The prevalence of HIV antibody was 28%.. slig'itly higier in fe - mfles.ne hhgwstsaxpnawdewe us bide 204% a; gxmpvdflia new uidwnxme bioldm ¥@& Seroprevalenoe increases with duration of addiction up to 9 years, beyond which it dscmes. In spite of free sale and large availability of syringes in Italy, needle sharing ms referred by 81% of interviewed DA. The relative risk (RR) of this practice m 4.07 (01.95%: £642.25); 3.63 for occasional sharing (& 11.08) and 6.10 for frequent sharing (lg-20:31). Needle sharing in prismiwas naxxied by name than 33% of DA with history of buriso1mmts. Detailed ssqafl history danmrnzated a ourslatflribetween minxn‘of pmnrxms/year (P/Y) and sang positivity (RR 1.83 for 3—10 P/Y; RR 1.90 for 11—50 P/‘I; RR 4.65 for 51 P/Y). Standardization for sex and/or needle sharing coifhned this asxciation. Having a shrub partner, even if DA, qxxmued to be protective. Homosemality was infleqmntly reported and not associated with sempositivity. At clinical exanination, 3 or now enlarged lyndatic sites were fomd in 20.4% of DA (64.8% of these were positive). RR of being positive in preserve of lyrrphadenophathy was 10.34 (gs—2.437). Sinceneedlesharirgandmnberofsexper'tnersseentobefl'ienostinportantriskfactorsinDA and seroprevalence in Turin is still low carpered to other italian cities, a timely and well planned cmtml progran could limit the spread of HIV infection. A follow up, now in course, will detenrune the hmxnt of this policy.“Free needles" omvxm be be nainstay in preventing HIV spread anxg DA HIV ANTIBODY PREVALENCE IN BLACK MINERS BETWEEN 1970 - 19114 M242 SHER R", ANTUNES E“, REID B“, FALCKE H“ xDept of Immunology, School of'Pathology of the University of the Witwatersrand and the South African Institute for Medical Research, Johannesburg, South Africa xxRand Mines South Africa. Between 1970 - 19TH a pneumococcol vaccine trial was conducted in black mine workers in South Africa. Aliquots of serum collected during this trial were stored at -200C. In November 1986 these sera were tested for antibodies to HIV. Participants in the trial came from Mocambique (1191), Malawi (1080), South Africa (171), Lesotho (55), Botswana (32), Angola (29) and Swaziland (16). As initial screening with the Abbott HTLV—111 EIA gave many false positives, all sera were tested with the Wellcozyme anti-HTLV-111 and positives were confirmed with indirect fluorescence, Elavia-EIA and Western Blotting. Eleven sera were found to be positive with the Wellcozyme test, six of which were positive with indirect fluorescence. These sera were negative with Elavia and Western Blotting Two sera, positive with Abbott EIA and indirect fluorescence but negative with Wellcozyme and Elavia, gave moderate staining with Western Blotting to P17, 2h, 35, 55, 56 and GPh1 and 120. One was from Malawi and the other Lesotho. This study fails to provide convincing evidence of HIV infection in Malawi, Mocambique and other Southern African countries between 1970 - 75. In a comparable group of mine workers surveyed in 1986 the prevalence of HIV infection was found to be 3.71% in Malawians and 0.07% in Mocambicans. TRANSFUSION-ACQUIRED HUMAN IMHUNODEFICIENCY VIRUS (HIV) INFECTION in NEONATES. W, 11.17. WYKOFF", R.J. BOYLE‘. ‘University of Virginia Medical Center, Department of Pediatrics, Charlottesville, VA. 'ISouth Carolina Department of Health, Greenwood, SC. Eleven neonates received blood from two HIV infected donors. All developed laboratory and/or clinical evidence of HIV infection, usually in the first year of life. Nine of 11 had serum antibody to HIV when tested between 9 and 16 months of ago; two seronegstive infants were severely hypogammaglobulinemic when tested. Nine patients developed a variety of illnesses characterized by hepatosplenomegaly, lymphadenopathy, chronic diarrhea, failure to thrive, and thrombocytopenia. Infections, including pneumonia, mucocutaneous candidiasis, and sepsis were a major source of morbidity and mortality. Two children have remained continuously asymptomatic. In follow-up ranging from two to four years, five patients have died, four others had HIV associated illnesses, but recovered and are now healthy. All patients had immunologic abnormalities; the most consistent finding was a decreased proportion of T—helper cells Three patients had panhypogammaglobulinemia. These infants had significantly lower numbers of T-helper cells compared to patients with normal or increased serum immunoglobulin concentrations (P=OD12). We conclude that exposure to HIV via transfusion in the neonatal period results in an extremely high rate of infection with substantial mortality and morbidity, but clinical recovery occurs in some patients. Second, hypogammaglobulinemia may be more common in infants with HIV infection than previously appreciated. M243 17 MH44 Status of AIDS in the Americas ST. JOHN, R.K., ZACARIAS, R., Pan American Health Organization, Washington, D.C. In 1983, the Pan American Health Organization initiated regionwide surveil— lance for AIDS. Because AIDS was confined almost exclusively to the United States, a very simple reporting system was installed based on the Centers for Disease Control's case definition. Member Countries were requested to report the total number of cases of AIDS and deaths due to AIDS every six months. The objective was to follow the spread of AIDS within the Region. This report summarizes the available data based on the PAHO surveillance system, as well as data from several special studies carried out in some of the countries. The data are sufficient to define the overall picture of AIDS in the Americas, although the exact magnitude of the AIDS problem is not known precisely in each country. The occurrence of opportunistic infections as markers for AIDS is variable throughout the Region. With some exceptions, the specific frequencies of certain infections are essentially the same as in the United States. Diar- rhoeal illness is more common in Haiti and generalized Mycobaccerium tuberculosis infection is more common in Brazil and the Dominican Republic. The homosexual/IV drug user patient profile common in the United States (Western AIDS) prevails in Latin America and the Caribbean, with a greater proportion of homosexual and bisexual men and a much smaller proportion of intravenous drug abusers. In the Americas, AIDS is predominantly a sexually transmitted disease. AIDS is a growing problem in the Americas, whose overall pattern, with the exception of Haiti, appears to be following the pattern established in the United States. (Source: Health_Situation and Trend Assessment Program (PAHO). MP45 Prognostic value of HIV antigen capture assay in a ' long-term prospective study of seropositive hemophiliacs. JEAN-PIERRE ALLAIN", Y.LAURIAN", D.A.PAUL‘, F.VERROUST"‘, M.LEUTHER", C.GAZENGEL**, et al., *Abbott Laboratories, N.Chicago, IL, HAIDS-Hemophilia French Study Group. Ninety-six hemophiliacs positive for HIV antibody entered a 28:6 month prospective study. Every 4-6 months they were monitored for clinical and biological parameters including 3 HIV markers: HIV antigen (HIV Ag), p24 and gp41 antibodies (Ab). Eight subjects were HIV Ag positive at entry and 14 became positive during the study 7—47 months after seroconversion. HIV Ag containing samples had low titer or undetectable p24 Ab but high titer gp41 Ab. In the HIV Ag negative group, 66 subjects had high titer of both p24 and gp41 Ab and a had low p24 Ab titer and high gp41 Ab titer over a 2-3 year period. Clinical comparison between the 22 HIV Ag positive and 56 HIV Ag negative subjects showed a significant increase in AIDS cases (2/0 p<0.05), immunodeficiency related infections (7/1 p<0.001), immune thrombocytopenia (8/6 p<0.001) and severity of condition according to the Walter Reed staging system (p<0.001). In this group of mostly asymptomatic subjects at entry, neither T4+ lymphocytes nor T4/T8 ratio appear predictive of clinical severity. These results strongly suggest that the detection of HIV Ag associated with low titer or undetectable p24 Ab is an indicator of HIV related clinical complications and could be used to select patients for entry in drug trials prior to the development of ARC or AIDS. M246 Antibodies to Human Immunodeficiency Virus in Clinical Patients Presenting Mononucleosis-Like Syndrome. JOSEPHINE MUSIMANN,A. KELLER.A. FLAVIAND.M. JUNG. Institute Virion. CH-BBDB Ruschlikon/Zurich.Switzerland. Serological tests were performed with cars of 401 patients clinically presenting a mononucleosis-like syndrome. Antibodies to Human Immunodeficiency Virus [HIV] were detected in 15 cases [3.7 percent}. A close correlation of positive results was obtained among enzyme immunoassay,Wastern blot (performed in two diFfarent laboratories],immunobihding assay,comolement-Fixation and indirect immunofluorescence. The high degree of agreement among the results of tests using different methodologies contributes to the significance of these (unexpected) positive results. HIV positive sara were also tested for other agents Known to cause infections or be reactivated in immuhocompromizad hosts. Thirteen out of 15 were saror positive for Cytomagalovirus.7/1S for Toxoplasma gondii,12/15 for Herpes simplex virus.1S/1S for Epstein-Barr virus and 0/15 for human Polyoma virus. No IgM antibodies were found to the above agants.excapt for one with Epstein— Barr IgM,and one with border—line IgM to this virus. Syphilis serology was uniformly negative. These results should encourage the tasting of Bars for HIV antibody in patients outside the so-called "risk groups”. This is justified.avan if the test is not rauuasted,sinca it is the only way to accumulate more epidemiolo- gical data on the spread of this infection. Historically similar studies have been performed on many other infectious diseases with excellent results. HIV should be no exception. MONDAY, JUNE 1 lflR47 Perinatal HIV infection: preliminary report of prospective study on 71 infants. JACQUELINE MOK+, Carlo Giaquinto*, Ilse Grosch—wbrner‘, Anthony Ades**, Catherine Peckham**, +Department of Community Child Health and City Hospital, Edinburgh, U.K., *Universita di Clinica Pediatrica, Padova, Italy, “University of Berlin Children's Hospital, West Germany, **Institute of Child Health, London, U.K. To define the natural history of perinatal HIV infection, three European Centres collaborated in a prospective study to determine the prevalence of infection in infants born to seropositive mother, and to document the clinical and immunologic outcome. Seventy-one children were identified at birth, and seen 3 monthly. Twenty—seven (38%) have been followed up for longer than 8 months. Forty—eight infants were delivered vaginally, 21 by caesarean section. Breast feeding took place in 7 infants. The clinical outcome in the infants could be grouped into the following: I - Asymptomatic (n = 60) II - Non specific signs (n = 4) which included unexplained lymphadenopathy, hepatosplenomegaly, neurodevelopmental abnormalities. III — HIV syndrome (n = 7). These infants presented with signs in II as well as recurrent/unusual infections, opportunistic infections, recurrent/protracted diarrhoea. No correlation was seen between outcome and mode of delivery, or breastfeeding. We propose a uniform classification for HIV disease in infants and children, separate from the one currently used for adult disease. MP48 AIDS in developing countries RICARDO MI. raculty of Medicine, University of 530 Paulo, Brazil. Brazil. with a population of 136 millims inhabitants has, in 1986.the secmd largest number of AIDS patients in the world. Around one thousand cases were notified up to Dec-bet 31,1986. sixty percent of such figures been notified in She Paulo. Considering the evident underreporting of infectious diseases and the fact that AIDS was not yet made compulsory for notification in this country. vary probably such numbers should be raised 50-1008. The perspectives for AIDS in Brazil, and as an extension in the amoral. are very pessimistic. Poor socioeconomic and cultural patterns of most of the po- pulation, added to poor housing. promiscuity and high prevalence of malnwri- shed people allow us to raise such dark predictions. Preliminary serological H.I.V. antibodies surveys have shown 53% of homosexuals, 39‘ of transvetites , 43‘ of hamophiliacs, at of renal haemodyalisis patients, 0.2-10! of blood d2 nets, 2‘ of prostitutes and 100% of full-blown AIDS patients, to be positive . Brazilian indi- living in the border to Venemsla did not show any evidence of past infection with the H.I.V. Also, blood drawn from Brazilian Navy sailors in l974, resulted negative for H.I.v. antibodies. Around 200.000 serological tests carried out in private blood banks in SEo Paulo city showed a 0.25% posi- tivity. In Rio 0.36% tests among 14.756 blood donors resulted positive for 11.1. V. antibodies. It was estimated that, in 1987, between 500.000 and one million Brazilians will be infected by the H.I.V. Based on an observation of one case of hepatic-splenic Schistosomiasis with AIDS we can speculate on the changing patterns of the histopathological pictures of a few endemic diseases such as Leishmaniasis, chagas' disease, Malaria, Tuberculosis, Leprosy, Dengue, Yellow fever and Paracoccidioidomycosis. MR49 Risk of HIV Seropositivity in Relation to Specific Sexual Activities of Sexual Contacts of Men with AIDS or ARC. RANDALL A. COATES, L. CALZAVARA, S.E. READ, M.M. FANNING, F.A. SHEPHERD, M.M. KLEIN, JR: JOHNSON, C.L. SOSKOINE, Faculty of Medicine, University of Toronto, Toronto, Ont., Canada. 244 male sexual contacts of men with either AIDS or ARC were recruited into a prospective study between July, 1984 and July 1985. At induction, data were col- lected on the sexual relationship between the sexual contact and his primary case, as well as data relating to sexual activity with other men. At recruitment , 141 sexual contacts had antibodies to HIV while 103 were seronegative. All seronegatives had last had sexual exposure to their primary cases at least three months prior to antibody testing. After adjusting for the number of sexual en— counters with primary cases and the number of other male partners, the following sexual activities with the primary case were significantly associated with sero- positivity in sexual contacts: receptive anal intercourse (O.R. (odds ratiol=3.4 , p<0.0001); insertive anal intercourse (O.R.=2.3, p<0.01); receptive fisting (0.R.=4.3, p<0.01); receive a dildo in anus (O.R.=3.9, p=0.002); mutual masturb- ation solely (O.R.=0.45, p(0.05). Similar results arose Wnen analysing data on sexual activities with men other than the primary case. Also, seropositivity was associated with sexual contact with men from U.S. centres (New York City O.R.= 2.4, p=0.003; Houston/Dallas 0.R.=3.7, p=0.002). Further, logistic regression models which simultaneously adjusted for sexual activities with primaries and other men, revealed that seropositivity was significantly associated with only receptive and insertive anal intercourse with the primary cases and sexual con— tact with men from Houston or Dallas. All seropositive contacts had either rec— eptive or insertive anal intercourse with primaries or other men. Oral sexual contact was never associated, significantly, with HIV seropositivity. 18 MP5“ Risk of HIV Seropositivity in Relation to History of S'I‘D's and Recr- eational Drug Use in Sexual Contacts of Men with AIDS or ARC. RANDALL LCOATES, L. CALZAVARA, S.E. READ, M.M. FANNING, F.A. SHEPHERD, M.M. KLEIN, J.K. JOHNSON, C.L. SOSKOLNE, Faculty of Medicine, University of Toronto, Toronto, Ont., Canada. 244 men who had had sexual contact with men with either AIDS or AIDS-related complex (ARC) were recruited into a prospective study between July, 1984 and July, 1985. At induction, data were collected on the sexual relationship bet- ween the sexual contact and his primary case, as well as data relating to sex- ual activity with other men, history of sexually transmitted diseases (STD's), and use of a variety of recreational drugs. At recruitment, 141 of the sexual contacts had antibodies to HIV while 103 were seronegative. All seronegatives had last had sexual exposure to their primary cases at least three months prior to antibody testing. After adjusting for number of sexual encounters with the primary case and other men, the following variables were associated significan- tly with HIV seropositivity in contacts: history of rectal gonorrhea (0.R. (odds ratio)=2.8, p 0.001); history of syphilis (O.R.=2.3, p=0.006); history of hepatitis (O.R.=2.9, p<0.0001); use of ethyl chloride (O,R.=2.8, p=0.007); use of 'uppers' (O.R.=2.3, p=0.006); and use of MDA (O.R.=2.4, p=0.004). Logis- tic regression models which controlled for confounding by specific sexual act- ivities with the primary case and other men revealed that history of hepatitis, history of syphilis, and use of MDA remained significantly and independently associated with HIV seropositivity. M251 The Epidemiology and Clinical Manifestations of AIDS in Israel. YARDENA SIEGMAN-IGRA*, S. MAAYAN**, S.D. PITlik***, T. SCHNARTZ#, C. COSTIN#, D. MICHAELI#, * Tel Av1v Med1cal Center, Tel Aviv, ** Hadassah University Hospital, Jerusalem, *** Beilinson Medical Center, Petah Tikva, # Ministry of Health, Jerusalem, Israel. As of Dec 11986, 23 cases of AIDS have been reported to the Israeli Ministry of Health among persons residing in Israel. In contrast to the experience in the United States and Europe, rates of AIDS were low and have progressed slowly during the last four years (0.5 - 0.75 cases per million). Risk factors for AIDS were identified in 22 patients: hanosexuality in 12 , hemophilia in 8 and receipt of blood transfusions in 2. Eleven of the 12 homosexuals have. most likely, been infected abroad, and all hemophilia patients had received imported connercial clotting factors. The two cases associated with blood transfusions received blood donated in Israel. The spectrum of clinical presentations and opportunistic pathogens was si- milar to that reported in the Western World, except for one case of Mycobac- terium Simiae systemic infection. Seroepidemiologic studies in 198 —86 suggest a low prevalence (<10%) of HIV antibody among homosexuals and IV drug abusers. Sexual relations abroad of persons at risk for AIDS and receipt of imported clotting factors are the most important risk factors for AIDS in Israel. Transmission of the virus among Israeli homosexuals seems to be infrequent at the current level of exposure to the virus. The low prevalence of HIV antibody in homosexuals and IVDA's suggest that Israel is a pre-epidemic area for AIDS. MP52 Assessing and Modelling Heterosexual Spread of the Hmnan Immunodeficienzy Virus in the United States VICIUR DE GRUTIOIA“, K. MAYER“, *Harvard Medical School, Bostm, MA, **Erown W RI. Epidemiological investigation of the AIDS epidenic among heterosesmals has been chiefly of two types: 1) studies of partners of individuals infected with the Hunan Immmodeficiency Virus (HIV) and 2) population surveillance. Although heterosexual partners of infected individuals (imluiing those without other risk factors) appear to be at high risk of infection, only a Shell proportion of total number of cases of AIDS have been attributed to heterosamal contact in the United states and Europe. To reconcile these findings, we develop an epidanic model for heterosecual spread of HIV infection and fit to airveillance data. Fitter parameter values are restricted to a range that is consistent with findings fran partner studies. Because, at present, most HIV—infected heterosexuals ard bisexuals have been infected through other means (IV drug use or hmosemal contact), the nodel considers two interacting populations: a $1611 pcpulation of jrflividuals rapidly infected by high risk activity and a large population of individuals at risk only frqn heterosexual contact. No precise predictions concerning the future of the AIDS epidanic among heta'osacuals is possible at this time, but current epideniological firdings do not appear to preclude a major heterosecual epidemic. Projections depend strongly on the delay between infection and infectivity. In addition to using the model for projection, it can also be used to examine the assumptions required for interpretation of results of case-control studies of HIV infection. MONDAY, JUNE 1 M353 HIV Antigenemia: Association with Decreased Numbers of T4-cells and Increased Risk for AIDS FRANK DE NOLF*, J. GOUDSMIV, D.A. PAUL“, J.M.A. LANGE*, C. HO0VKAAS***, ** et al. *Academic Medics) Centre, University of Amsterdam, “Abbott Laboratories, North Chicago. Ill., ***Dept. of Infectious Diseases, Municipal Health Ser- vice, Amsterdam, The Netherlands Sequential serum samples of 256 HIV antibody (HIV-Ab) seropositive and sero- converted homosexual men, participating in a prospective study on the preva- lence and incidence of HIV infection and risk factors for AIDS, were tested for HIV antigen (HIV-Ag). Forty (20.2%) of 198 HIV-Ab seropositives were HIV antigenenic throughout the study period of an average of 19.3 (t 0.5) months. Among the remaining 158 HIV-Ah seropositive individuals and 58 HIV-Ab serocon- verters 28 became HIV-Ag seropositive (attack-rate 14.3%). 114 (44.5%) of the 256 remained asymptomatic during the study period. Constitutional disease developed in 39 (15.2%) and was seen more frequently among HIV-Ag seropositive than among HIV-Ag seronegative individuals (p ( 0.00001). AIDS developed in 15 men; the AIDS attack-rate was 23.9% in the HIV-Ag sero- positive and 1.3% in the HIV-Ag seronegative group (p 4 0.00001; 0 = 23.292). The wean number of T4+ cells declined during HIV-Ab seroconversion and stabi- lized at a significant (p < 0.05) lower level in individuals seroconverting or seropositive for HIV-Ag than in individuals without HIV-Ag after HIVva sero- conversion. This indicates that low and declining numbers of T4+ cells may herald HIV-Ag seroconversion. The risk to develop AIDS and related disease appears to be strongly associated with persistent HIV antigenemia. MP54 Natural History of HIV Infections in l-Iaerophiliacs AKNSIAM, A; VESSEF, M; ROY, A. Treloar Haenophilia Centre, Holybourne, Alton, Hampshire, U.K. The natural history of HIV infectim omtdnues to unfold and ongoing data is crucial. We have studied 48 HIV positive haerophiliacs. In 32 of these we were able to postulate the of semcmversim through retrospective sanpling. These were 1980 (1), 1981 (5), 1982 (10), 1983 (11) and 1984 (5). In the renaming 16 patients the year of serooonversion was no later than 1980 in l, 1983 in 3, 1984 in lo and 1985 in 2. No case of AIDS has developed in our group. Seventeen (35%) have persistmt generalised lynphaderxpathy (Pm) and 7 (15%) are thrurbocytopenic. Pat. was first noted within the Imawn year of setooonversion (year 0) in one patient, year 1(1), year 2(1), year 3 (3), andyear 4 (3). ’l‘hepresenoe ofPGLwas not significantly correlated with tine since semcmversion nor with T helper cell ('1‘4 ) levels, although 5 of the 9 patients with lowest 'I‘4 levels had PGL. levels were measured in 36 patients and were subnormal in lo (28%). Seréccxwersion year was known in 21 of these and a significant negative correlation between tine since serocmversion and '1‘ levels was found (r = .55 p =<.001). ‘IheneanT level in 9patie1tswmwere lam tohave seroconverted more than 4 years pgeviouslywas .91 x 10 9/L, while the mean level in 12 patients who had sezooonverted less than 4 years previously was 1.8 x 10 9/L. The difference is highly significant (p = «(131). InspiteoftheabsenceofAmSsofarmourpatients,webelievethatthe progressive reducuon 1.11 T levels with time portends an ultimately high incidence of serious AIDS, althmgh the incubation period appears to be longer than in other high risk groups. MP55 Continuing Surveillance of HIV Associated Morbidity and Mortality in 3 Well Defined Population PETER JONES, MAUREEN A FEARNS, LINDA MCBRIDE, P HAMILTON, Newcastle Haemophilia Centre, Royal Victoria Infirmary, Newcastle Upon Tyne, United Kingdom. In September 1985 we reported Clinical and laboratory Findings in 337 people in Northern England, including 143 multi—transfused haemophilic patients (Jones P, et al, AIDS and haemophilia: morbidity and mortalityin a well defined population, British Medical Journal 1985, 291, 695-9). Of 99 severely affected haemophiliacs 76 were anti—HIV seropositive; 3 of 36 female sexual partners then tested were also seropositive. At the time of publication 3 of 4 patients with AIDS had died. 15 months later a further 9 patients have developed AIDS; 4 are dead. One of these patients was the wife of a sero— positive haemophiliac who developed pneumocystis carinii pneumonia and dementia A further seropositive partner has given birth to a seropositive but clinically well child. The third seropositive female remains clinically well. 51 other female sexual partners have been tested and are seronegative; A1 had sero- positive and 10 seronegative partners. Four of those presenting with AIDS had no clinical markers suggesting impending illness other than seropositivity at the initial survey; 2 presented with extra-cerebral lymphoma. A further patient with abdominal lymphoma is presently receiving treatment. Whilst the prognosis for anti-HIV seropositive haemophiliacs remains un- certain these results suggest that AIDS may prove to be more common than earlier predictions for this population first indicated. Heterosexual trans- mission of HIV is less common than expected. 19 MP56 Heterosexual Transmission of HIV in Switzerland I ALINE JANETT, T. STUTZ, B. SOMAINI, H. VORKAUF, M. KAUFMANN, Swiss Federal Office of Public Health, Berne, Switzerland Various sources are drawn on in Switzerland for the evaluation of the epide- miological situation. In addition to the case of AIDS reported, we also recei- ve information on the persons who attend the anonymous test units or of blood donors whose HIV antibody tests show a positive result. Furthermore, all posi- tive laboratory results are submitted in collective reports. The following re~ sults were obtained by end 1986. Cases of AIDS: of the 165 cases of AIDS in adults, 150 (=91 a) were men and 15 (=9 %) women. In the case of 6 of the Swiss men and 5 of the Swiss women, heterosexual transmission of HIV is reported as the sole risk situation. Blood donors: of the 52 cases of HIV antibody p051tive blood donors analyzed to date, 43 (=83 t) are male and 9 (=17 %) female. 5 (=12 %) of the men and 2 (=22 %) of the women reported heterosexual contacts as the sole risk situation. Anonymous test: 335 of the men tested reported Varied heterosexual contacts as sole risk situation. 4 (=1.2 %) of these were HIV antibody positive. of the corresponding 178 women tested, 3 (=1.7 %) were HIV antibody posxtive. Laboratory reports: Of the 4,268 HIV antibody positive reports, 3,lll (=73 1) are accounted for by men and 1,157 (=27 9) by women. Summary: Heterosexual transmiSSIon of HIV can already be well documented to- day. The relevant measures to prevent increasing heterosexual transmission are imperative. HIV Antibodies in Seroconverters Followed by Weekly Intervals MR57 MR LAURITZEN*, B. KVINESDAL', B.®. LINDHARUI‘“, A—G. POUISEN", *AIDS-Iaboratory, Rubella Department, Statens Senmdnstitut, Copenhagen, "La— boratory of ‘Iunour Virology, ’Ihe Fibiger Institute, Copenhagen, Denmark. Sera frcm 26 patients were analysed for HIV—antibodies by five different me— thods. The patients were initially sermegative and became positive. The ana— lyses were an indirect ELISA with HIV—antigen from H—9 cells (A), a oarmercial indirect ELISA, BLAVIA, with antigen fro-n (324 cells (B), a comercial carpeti— tion ELISA, Wellcozyne (C), a western blotting for HIV specific IgG (D), and a western blotting for specific IgG, IgA, and IgM antibodies (E). The first serum sanple, which was positive by the screening test, (A), defined the day of serooonversion. Sera frcm 10 different patients were collected within 1—4 weeks before sero— conversion, where 4 were positive by (B) and 3 by (D) 1-2 weeks before (A). A singular reactivity on HIV-antigen p24 was observed for 6 patients by (D) and for 7 patients by (B) 1—3 weeks before (A). Sera fron 9 patients were collected 5—10 weeks before seroconversion. In this period 4 were positive by (B), 2 by (C), and 2 by (D) and (E), while they were borderline by (A). In the same period 3 sera were borderline by (A) and p24 reactive in (D). Only four sera shamed borderline reactivity before this period. Western blotting analyses were reactive earlier than the ELISA screening test. Sane patients were clearly seropositive 1-2 weeks before they were iden- tified by the ELISA screening method. These patients would escape the HIV an— tibody screening test. M258 Absence of HIV infection in two sentinel cohorts of high—risk black South Africans. SUSAN F. LYONS, BARRY D. SCHOUB, ALAN N. SMITH, SYLVIA JOHNSON, GILLIAN M. MCGILLIVRAY, MRC AIDS Virus Research Unit, National Institute for Virology, Private Bag X4, Sandringham 2131, South Africa. As at the end of 1986 no cases of AIDS had been recognised in black South African individuals; all 38 reported AIDS cases in South Africans have occurred in white males belonging to the high-risk groups characteristically seen in Western countries. To determine the possible introduction of HIV infection from African countries to the north, two cohorts of promiscuous African women, 56 black prostitutes "servicing" a large industrial complex north=east*of Johannesburg and 195 black females attending the major Johannes— burg clinic for sexually—transmitted diseases (STDs) were investigated for the presence of HIV infection. All sera were examined for HIV antibodies, both by ELISA (ELAVIA - Pasteur Institute) and by indirect immunofluorescence (IF) using HIV-infected H9 cells (obtained from Dr R Gallo). None of the prostitutes and only one of the STD attendees were positive for HIV antibodies (both by ELISA and IF); the latter individual was, however, a migrant Malawian and not South African. Examination of these specimens for other STDs revealed prevalences consistent with those seen for similar populations elsewhere in Africa. In the prostitute cohort, 24 of 56 (43%) were HBsAg or anti-HBs positive and 53 of 56 (95%) were positive for chlamydia antibodies. Similarly, in the STD cohort, 81 of 195 (421) were positive for HBsAg or anti—HBs, 27 of 108 (252) were HR positive and 179 of 195 (92%) were positive for chlamydia antibodies. There thus appears to be still no evidence of the spread and establishment of endemic African AIDS in South Africa. MONDAY, JUNE 1 M259 T-Lym hocyte Subsets in HIV Infected Drug Abusers and Long-Term B aine A st rs J.R. ROBERTSON*, CAROL A.SK|DMORE*, M.STEEL**, D. BEATON**, *Edinburgh Drug Addiction Study, Scotland, **Western General Hospital, Edinburgh, Scotland A study group of HIV infected IVDA, unique in 2 ways. Firstly, we have been able to pinpoint seroconversion dates, thereby excluding the possibility of different subgroups with different lengths of seropositivity. Secondly, the group comprises some long-term abstainers who are antibody positive, thus it has been possible to follow the clinical course of infection in both abstinent and current lVDA. In infected IVDA the presumption is often that continued use of drugs may increase the likelihood of progression to AIDS. To determine the relationship of continued drug use to apparent disease progression, as measured by Tu/Tg cell ratio, 10 abstinent and 10 current drug abusers had blood samples tested for Th/Tg ratio. Both groups had been sero- positive for the same length of time. Significant differences emerged in the ages of the two groups, the abstinent group being older (p< .05, 18 df). This group also had a significantly shorter length of heroin use (p< .005, 18 df). The Th/Tg cell counts were not significantly different. These results suggest that no advantage is shown in those stopping heroin use, since in a comparable seropositive group abstinent from opiates (including methadone) Th/Tg ratios continued to be unfavourable. The provision of methadone for seropositive IVDA may be less appropriate than reducing the risks to those who remain seronegative. Mnso Early Indications of Unidirectional Heterosexual Transmission of AIDS in Botswana WILLIAM D. OSEI, E. T. MAGANU, W. MANYENENG, R. K. VYAS, J. VAN DAM, L. MAHLOANE et al., Ministry of Health, Gaborone, Botswana. Botswana is situated south of the high prevalent regions of AIDS in Africa but has identified only 7 cases in the past 2 years. Transmission is presumed to be predominantly heterosexual. 23 sexual partners of these cases have been followed and tested. 211 in— fectious diseases in-patients at 10 selected health facilities in the country were also screened for HIV infection. The majority of cases (85.7%) are females who also constituted 61.5% of the positives among the health facility surveys. Approximately 62% of all known HIV infected individuals are females. 3 females who had evidence of HIV infection.maintained one positive sexual partner each and at least another who remained uninfected over the period. In ocrly stages of AIDS in Botswana,it appears that males are more difficult to be infected than females who are therefore at a higher risk in a hetero- sexual relationship. This female preponderance is in excess of the sex dis— tribution in the general population as well as the study population. Differences in the anatomy and the physiology of the sexes and the varying have been given as SBEETZE_EEE'?EEEors for this male to female transmission in Botswana. Definitive conclusions must await further follow—up. M261 HIV Infection in African Children with Sidtle Cell Anemia BOSENGE N'GALY*, K. KAYEMBE", J.M. MANN***, R.W. RYDER’, H. MBESAfifi, H. FRANCIS* et al., *Projet SIDA/Zaire, **University Hospital, Kinshasa, **0 CDC, Atlanta. To assess the importance of transfusions and injections in the trans- mission of HIV and to define the clinical spectrum of HIV infection in children with sickle cell anemia (SCA), we studied 241 children with SCA (aged 1-12 yrs; mean 6 years). We compared these patients (124 boys, 117 girls) with 126 non-sickle cell (NSCA) children (64 girls, 62 boys) of the same age. Thirteen SCA children were HIV(#) (5.4%) compared to l (0.8%) of the NSCA group. Seropositivity in the SCA roup was associated with increased lifetime numbers of transfusions Imean 5.8 in HIV(+) patients(P) vs 3.4 in HIV(-)P] and the receipt of blood from paid donors (67% in HIV(+)P vs 52% in HIV(-)P) but not with the number of injections during the last 5 years (mean 76.5 in HIV(+)P vs 78.7 in HIV(-)P. Among SCA children HIV(+), patients were more likely than HIV(-) patients to present with failure to thrive (62% vs 21%, p<.001), polyadenopathy (62% vs 37%, p4.05), weight loss (38% vs 24%) or unexplained fever (23% vs 11%) Transfusions in Africa appear to be a more important source of HIV infection in patients with sickle cell disease than injections. The pediatric spectrum of HIV infection in African sickle cell patients is similar to the one described in African children without sickle cell disease. 20 Inpsz Detection of HIV Antibodies in Whole Blood Impregnated ' Filter Paper Discs BJARNE fl. LINDHARDT*, I.C.BYGBJERG**, H.D.PETERSEN**, I.LAURSEN**, B.FREDERIKSEN**, *The Fibiger Institute, pitalet, Copenhagen, Denmark. Eluation of HIV antibodies from whole blood impregnated filter paper (Whatman SMM Chr) was performed by punching out a 14mm disc from the filter paper and eluating the antibodies in 2.5 ml PBS + 0.1% Tween 20 + 12 normal rabbit serum + 0.015 M NaN for 2 hours at room temperature. This correspond to a serum dilugion of ap- proximately 1:100, and the eluate is tested in ELISA (undiluted) and immunoblotting (diluted 1:5). Corresponding serum and whole blood discs from 15 Danes and 16 East Africans were tested, as were serum discs and whole blood discs from 42 Central Africans. A 100Z correlation was found in both ELISA and immunoblotting by testing serum and whole blood discs from Danes and East Afri— cans, of whom 5 and 3 were found HIV antibody positive, respecti- vely. Likewise, testing of serum discs and whole blood discs from Central Africans, of whom 4 were antibody positive, revealed full agreement in both ELISA and immunoblotting. Whole blood eluates produced a slight but insignificant increase in 0D values of the ELISA as compared to ordinary serum. No significant loss of antibody activity was observed neither in the eluates after storage for 3 months at ~20 C nor in the filter paper discs after storage for 3 months at +40C. This technique may be useful to fa- cilitate sample collection and transportation, particularly in remote areas of the world. K.ULRICH*, **Rigshos- M263 illigsSydney AIDS Project: Factors Associated with Progession to BRETT TINDALL*, D.A.COOPER*#, J.BURCHAM*, B.DONOVAN**, T.BARNES**, R.PENNY#. *NHAMRC Special Unit in AIDS Epidemiology and Clinical Research, Sydney, Australia. #St. Vincent's Hospital, Sydney, Australia. ** Private Practice. In a prospective study of 996 homosexual men, 386 (38.8%) were HIV sero- positive at enrolment. In 3 years, 32 of these seropositive men (8.3%) have developed AIDS. Compared with seronegative subjects, seropositives were more likely to have performed receptive or insertive anal or oral sex in the three months prior to enrolment. Immunologically, seropositives had a significant lower TA+ lymphocyte count and T4+:T8+ ratio and an increased T8+ lymphocyte count, compared with seronegatives. Seropositives who developed AIDS reported greater use of marijuana in the previous 3 months than did seropositives who did not progress but the two groups did not differ on other lifestyle variables. Splenomegaly and hepatometaly were detected significantly more frequently as antecedent signs in subjects who developed AIDS. The absolute TA+ lymphocyte count was the most reliable antecedent indicator of development of AIDS. At enrolment (a median of 8.5 months prior to diagnosis) subjects who developed AIDS had a significantly lower TA+ lymphocyte count and TA+:T8+ ratio than did their non-progressing counterparts. Overall these findings support the acquisition of HIV infection development of AIDS. This study the best measure of progression. the role of the established risk factors for but have found no such co—factors for the emphasises the value of a low TA+ count as MP64 Epidemiology of AIDS in Australia. ' BRUCE M. WHYTE*, A.J.DOBSON#, J.GOLD*, D.A.COOPER*. *NH&MRC Special Unit in AIDS Epidemiology and Clinical Research, Sydney, Australia. # University of Newcastle, NSW, Australia. Since the first case of AIDS was diagnosed in Australia in late 1982 there have been an additional 376 cases diagnosed including 1A women, of whom 200 have died. The majority, 88%, have been homosexual and bisexual men, but 27 or 7% have been transfusion associated, 13 of them women. To the end of 1986 there has been only one case resulting from intravenous drug usage, although an additional twelve were homosexual/bisexual men who also used intravenous drugs. Two cases have become infected as a result of heterosexual intercourse. The initial diagnosis of AIDS was an opportunistic infection in 74% of cases and Kaposi's sarcoma in 18%. A further 3% were diagnosed with both opportunistic infection and Kaposi's sarcoma. Non—Hodgkin's lymphoma was the presenting disease in 5%. A mathematical model based on a Poisson distribution was developed using the numbers of cases among homosexual and bisexual men from 1982—1986 to predict the future case load of AIDS. To those numbers, a constant figure of ten cases annually was added to account for those cases belonging to other groups. Using this model, we have predicted 500 new cases in 1988 and 1000 new cases in 1990. The cumulative total to the end of 1990 would be 3000 cases. The epidemic of AIDS in Australia is following a similar pattern to that found in other western countries, with greatly increased numbers predicted in future years. MONDAY, JUNE 1 MP65 Risk of AIDS after herpes zoster. MADS MELBYE*, R.J. GROSSMAN**, J.J. GOEDERT***, R.J. BIGGAR***, E. EYSTER****. *Institute of Cancer Research, Aarhus, Denmark, ** Private practice, New York, N.Y., *** National Cancer Institute Bethesda, MD, **** Milton S. Hershey Medical Center, Pennsylvania. All patients diagnosed with herpes zoster (N=112) between 1980 and mid—1986 in a closed internal medicine practice for homosexual men in Central Manhattan were evaluated with respect to time of eventual AIDS development or death. Using Kaplan-Meier survival analysis 22. 8% (+/- 5. 3%) developed AIDS within 2 years after her— pes zoster, and 45.5% (+/-11.1%) after 4 years. The longest obser— vation period was 6 years, at which an estimated 72. 8% of the men had been diagnosed AIDS. Severity of the zoster (relative risk, RR =4. 6), the degree of pain (RR= 3. 4), and zoster of the cranial or cervical dermatomes (RR=2.2) were all associated with a poor prog- nosis. other clinical conditions which additionally increased the risk of AIDS included: oral thrush, oral hairy leukoplakia, amebi— 3515, and superficial (tinea) fungal infections. Oral thrush and oral hairy leukoplakia manifestations were diagnosed an average of 1.2 and 1.1 years, respectively, after the diagnosis of herpes zoster, making zoster an early indicator of an impaired immune sys— tem. Among hemophiliacs, the period between the development of hu- man immunodeficiency virus (HIV) antibodies and zoster ranged from 21 months to 88 months, with a median estimate of 56 months. Add— ing the interval between HIV-seroconversion and zoster to the pos— sible interval between zoster and AIDS, the risk of developing AIDS after HIV-seroconversion must continue at least 10-15 years. MP56 Oadxtspiralfltddahmalitisinlnmseual/bisaaalmwithand widrut*W Wows mom“, mm“, DEM, DEM, R.T.JCHIBN*, B. F. PD Ihe Jdrs Ikrkins thuxexsity *Sdrxn of Mafirine and ** derd of Hygnae and Riflic Heath, Balthmxe,PI» anitheFlfltifiuater Airs dext shay nanzrsyiuatdc nmuimnhb Criebnxzfirai fluid (CEO was citainsi than 7 aqudzmati: senxrsitive during 30 mania of ctservaticn GEXD, and 01 levdxh nanxrsyduemric squzns, inahxfirg Sniaismxpasfiuxe > 30 maths an», 5 saxxxrwezters (SQ. nEn v11: had trxxane HIV- GF midi-res am em _'IUbal SP SC ASC ass) 0&5) 0*”) “#1” SF L>5 NBC/a1 Inn) 1 (20%) 3 (60%) 2 (29%) 6 (35%) Oligoolmal bans (>1) 1 (20%) 3 (60%) 3 (43s) 7 (41%) Elevated 190 index (>0.8) o o 3 (43%) 3 (13%) Positive HIV adore 1 (20%) o 1 (14%) 2 (12%) Pcsitive p24 andgen 0 1 (20%) 1 ( 6% CS? ties are crmnrn n1 HIV— Ixzmrsmual nan, wifli or vdthcut A case of Acquired Immune Deficiency Syndrome without the Recognised MP'B-I Risk Factors * PAUL GRINT*, M. RADEMAKER*, M. B. McEVOV, *St Bartholomews Hospital, London, **PHLS Communicable Disease Surveillance Centre, Colindale, London. Whilst the modes of transmission of HIV infection are now well established, it is important to retain a clinical awareness of the possibility of this infection in patients without apparent exposure to the recognized risk factors. We report two cases of AIDS, apparently without the usual exposure factors, in whom a temporal association was detected after detailed epidemiological investigation. The index case -a 45 yr old housewife, who developed Pneumoc stis carinii pneumonia following a severe herpes zoster infection, and was shown to Be anti-HIV positive. Three years prior to diagnosis she had been investigated for "glandular fever” and subsequent generalised lymphadenopathy, but no diagnosis was made. Detailed social history revealed no exposure to the relevant risk factors. However, three months prior to the onset of the "gland- ular fever”, she had provided terminal home nursing care for a 33 yr old Afric- an man, who died from an undiagnosed encephalitis. At this time she had un- covered skin lesions on her hands. Review of post mortem pathology specimens allowed a retrospective diagnosis of AIDS with cerebral toxoplasmosis to be made for the African man. The type of home nursing care given by index case, was quite different from that normally provided by health care workers with the training and facilities to prevent the spread of infection. 21 Related AIDS Study Group, MEGS Classification of HIV Infection in the Third World JEAN W. PAPE*, M-M. DESCHAMPS**, S. KELLIE*, R-I. VERDIER**, w.p. JOHNSON*. Cornell Univ. Med. Coll. NY*, GHESKIO, Port-au—Prince, Haiti**. 405 patients were referred to our AIDS clinic in Port-au—Prince, Haiti from July 1983 to June 1985 for diagnostic evaluations. HIV antibody (wv, p24, gp 120) was detected in 339 pts. (847.). Seropositive subjects were categorized based on their initial clinical evaluation and recategorized 1 yr. later. The signs and symptoms of patients in groups 2—5 were present for H month. Group 2 pts. had only prurigo. Group 4 had oral thrush alone (21) or with either the (18), S.enteritis (5) or khzoster (4). Group 6 met CDC criteria. During a 1 yr. period 4/7 group 1 pts. developed thrush and 226/293 (77%) group 2—5 pts. died or met AIDS criteria. The 66 HIV seronegative pts. initially evaluated had other diagnoses (pul tbc, typhoid, malaria, giardiasis, etc). We conclude that wgt. loss with either fever or diarrhea is the most common presentation of AIDS and that prurigo is an early finding with a poor diagnosis. This classi— fication defines the spectrum of HIV infection in Haiti. Group Number of Patients (Z) Initial Evaluation One Year Evaluation 1 Asymptomatic 7 (2) 3 (I) 2 Prurigo 29 (9) 7 (2) 3 Adenopathy 7 (2) 1 (< 1) 4 Oral thrush 48 (14) 36 (ll) 5 Weight loss and either 209 (62) 27 (8) fever or diarrhea 6 AIDS 39 (11) 211 (62) 7 Dead —- —- 54 (16) MRBQ Kaposi's Sarcoma and AIDS in Haiti (1979-1986) BERNARD LIAUTAUD*, 1.”. PAPE**, M-M.DESCHAMPS*, R-I. VERDIER*, A.C. LAROCHE*, F. THOMAS*, W.D. JOHNSON, JR.**, GHESKIO, Port-au-Prince, Haiti*, Cornell University Medical College, N.Y. **. We evaluated and treated 584 AIDS patients in Port-au—Prince, Haiti from June 1979 to December 1986. Kaposi's sarcoma (KS) was present in 53 patients (9%). The percentage of AIDS patients with KS has decreased from 15% (1979—83) to 5% (1985-86). KS lesions were the exclusive or predominant manifestation of AIDS in 32/53 (60%) patients, while the other 21 (40%) patients presented with opportunistic infections (OI). KS lesions were disseminated in 60% of cases with skin, lymph nodes, gastrointestinal tract and lungs as the common sites. Male predominance was more marked for KS patients (92%) than for 01 patients (72%). The annual percentage of female KS patients has been constant over time while the percentage of female OI patients increased from 14% to 28%. KS patients were comparable to those with OI in terms of age, socioeconomic status, place of residence and risk factors. 15% of KS males and 20% of OI males were bisexual, with other risk factors (blood transfusions, IV drug abuse) noted in 18% and 11%, respectively. Pruritic skin lesions (prurigo) were present in 23% of KS and 51% of OI patients. HIV antibody was detected in 96% of KS patients tested and also in 83% of their heterosexual sex partners. Kaposi's sarcoma in Haiti is clearly associated with HIV infection, is decreasing in prevalence, and is not associated with any particular risk factors. MR7" Prospective Study of AIDS in Hemophiliacs with Elevated Interferon Alpha Levels M.E. EYSTER*, 0.1. PREBLE**, J.J. Goedert* , The NCI Multicenter Hemophilia- *The Pennsylvania State University College of Medicine, Hershey, PA, **The Uniformed Services University of Health Sciences, and ***The National Cancer Institute, Bethesda, MD. We have previously shown that an acid labile form of alpha interferon (IFN) was persistently elevated in the sets of 3 hemophiliacs prior to the onset of AIDS. The prevalence and predictive value of serum IFN quantitated by a semimicrobiological assay (NEJM 1983: 309, 583-586) was assessed in 469 HIV seropoeitive and 346 seronegative hemophiliacs. Results at entry were as ** follows: IFN of the 43 HIV pos. IFN pos. (28 IU) hemophiliacs, <8 ID 38 ID 7 had AIDS and ll developed AIDS within 16 months (42%). Four more (9%) had AIDS-related symptoms. - 315 31 (9%) Twenty-one (49%) have remained well up to two HIV ————————————————— years. Four additional patients converted from IFN + 426 43 (102) neg. to p05. prior to the development of AIDS during the study. In a subcohort of B4 hemo- philiacs with HIV seroconversion dates, very high IFN levels (320 IU) predicted AIDS up to 1 year before diagnosis, even when controlled for duration of HIV infection (p5 .004). In conclusion, the prevalence of IFN in HIV seropositive hemophiliacs was 10%. At least 42% (18/43) had AIDS (16%) or preAIDS (26%). Persistently elevated IFN, especially high levels, usually heralded the onset of AIDS in one year. The role of IFN in the pathogenesis of AIDS has not yet been determined. However, its predictive value may be complementary to quantitation of T cell subsets. MONDAY, JUNE 1 M271 Human Imnunodeficiency Virus (HIV) Infection in Spouses of HIV Sero- positive Active Duty Navy and Marine Corps Personnel MARGAN g, CHANG, T.R. ZAJDONICZ, Naval Hospital Portsmouth, Portsmouth, Va. iEe United States Navy is conducting a Navy—wide HIV screening program of ali active duty personnel. All personnel found to be HIV seropositive are referred to one of four major evaluation centers. To date, 324 HIV positive active duty personnel have been evaluated at Naval Hospital Portsmouth. Thirty-three percent of these individuals are married. Evaluation of these dependent spouses was offered to all HIV seropositive personnel. No spouse in the inmediate geographic area refused evaluation. Thirty-four spouses have been evaluated. Ninety-four percent (32/34) were female; 6% (2/34) were male. Mean age of evaluated spouses was 27 years with a range from 16-42 yrs. Forty-four percent (15/34) were white. 41% (14/34) were black, 9% (3/34) were Oriental, and 6% (2/34) were Hispanic. Risk factors for HIV infection in spouses included being the steady sexual partner of an HIV positive spouse (85%), being the recipient of multiple blood transfusions (9%), and being bid sexual (3%). Thirty-five percent (12/34) of all spouses evaluated were HIV seropositive. Among spouses where the only risk factor was an HIV seroposi- tive spouse, the seropositivity rate was 29% (8/28). Among 32 female spouses evaluated, three (9%) had AIDS or ARC. Nineteen percent (6) of female spouses were pregnant at the time of evaluation. One pregnant woman was HIV seropositive. Two HIV seropositive children have been detected. Dependent spouses of HIV seropositive active duty personnel are at signi- ficant risk for acquisition of HIV infection. This population is young, fe- male, and actively engaged in child bearing. Evaluation and counseling for spouses and children are essential to any large-scale HIV infection screening program. M272 Serologic Evidence for Infection by HIV-2 in Guinea Bissau in 1980. PATRICIA N. FULTZ*, W.M. SWITZER*, C.A. SCHABLE*, R.C. DESROSIERS**, D. SILVA**, and J.B. MCCORMICK***, *AIDS Program and ***Division of Viral Di- seases, Center for Infectious Diseases, Centers for Disease Control, Atlanta. CA, **New England Regional Primate Research Center, Harvard Medical School, Southborough, MA. Human immunodeficiency virus type 2 (HIV-2, originally called LAV—Z) was re- cently isolated from AIDS patients from the West African countries of Cape Verde and Guinea Bissau. HIV-2 is more closely related to the simian immunodeficiency viruses (SIV) than to HIV—l both serologically and by nucleic acid hybridization To determine the past prevalence of HIV—2 in some areas of West Africa, we test— ed 440 Serum samples collected in Guinea Bissau in 1980. The samples originally were collected to test for the prevalence of antibodies to Lassa virus in adults living in rural areas. He first screened the serum for antibodies to an HIV- like virus by ELISA using purified SIVmac as antigen. A large proportion (30%) gave 0D readings greater than 0.5, which was peculiar to human serum because a large number of monkey serum (195 of 214) from Africa gave 0D readings less than 0.2 in the same SIVmac ELISA. All of the human samples with 0D readings greater than 0.9 (28) were tested by immunoblot and immunofluorescence assays for anti— bodies to SIV/SMM, HIV-2, and HIV—1. Five human serum samples were repeatedly reactive by all assays to both HIV-2 and SIV/SMM. Antibodies to £35! £23, and pol gene products of HIV-2 and SIV/SMM were detected on immunoblots. Five of 2Z0 human sera were positive for antibodies to HIV-l using the Abbott HTLV-III EIA kit, but none could be confirmed as true positives by immunofluorescence and immunoblot assays. Thus, in 1980, 1.1% (S of 440) of a random sample of persons in Guinea Bissau had been exposed to a virus highly related to HIV-2 and SIV/SMM, but there was no evidence of infection by HIV—1. M273 Absence of Association between HIV Seropositivity and Plasmodium falciparum Malaria in Kinshasa, Zaire. PHUC NGUYEN-DINH‘, A. E. GREENBERG*, R. H. RYDER**I***, J. M. MANN**:***, N. KABOTE****, H. FRANCIS**:*****, et al., * Malaria Branch, Centers for Disease Control, Atlanta, GA, ** Projet SIDA, Ministry of Health and Social Affairs, Kinshasa, Zaire, *** AIDS Program, Centers for Disease Control, Atlanta, GA, **** Mama Yemo Hospital, Kinshasa, Zaire, ***** Laboratory of Immunoregulation, National Institutes of Health, Bethesda, MD. Because Plasmodium falciparum malaria and HIV infection coexist in several areas of Africa, the relationship between these two entities was investigated at the Mama Yemo Hospital (MYH) in Kinshasa, Zaire, between July and December 1986. Among 333 children evaluated at MYH, the HIV seropositivity rate in children with 3. falciparum malaria (1.22) was not significantly different from that in asymptomatic, healthy children (0.6%). Among 1046 children presenting at MYH for various medical complaints, no significant difference was detected between the HIV seropositivity rates in 540 children infected with P. falciparum (2.81) and in 506 uninfected children (4.9%). Among 1156 healthy adult MYH employees, a malaria slide positivity rate of 6.21 and an HIV seropositivity rate of 6.0% were found, with no association detected between these two variables. In an ongoing study in pregnant women delivering at MYH, the first 195 patients had a 3. falcipgrum infection rate of 19% and an HIV seropositivity rate of 7.21, with no association detectable. This overall absence of association indicates that E. falciparum does not act as an important opportunistic agent in individuals infected with HIV in Kinshasa. 22 MR74 Analysis of the AIDS epidemic in The Netherlands in comparison with data from the San Francisco CDC study cohort HANS A.M. VAN DRUTEN*, TH. DE 300*, J.C. JAGER**, S.H. HEISTERKAMP**, R.A. COUTINHO***, E.J. RUITENBERG**, et al.,*University Nijmegen (MSA), The Nether- lands, **National Institute of Public Health and Environmental Hygiene (RIVM), Bilthoven, ***Municipal Health Service, Amsterdam Using data from The Netherlands and the San Francisco CDC study cohort Mathe- matical models were formulated to estimate a) the annual effective contact rate i.e. the average number of sexual contacts per person per year that results in transmission of HIV and b) the number of homosexual men already infected from the cumulative number of persons with AIDS. If there is a delay of 3 years, 20,000 homosexual are assumd to be at risk in The Netherlands in the initial stage of the epidemic and the annual effective contact rate is estimated to have a value between 1.0 and 1.2. The width of the interval depends on the initial growth rate of the epidemic and the average du— ration of the infectious period in persons infected with HIV. The results indi- cate that the probability of transmission of HIV per sexual contact is low. Given 200 homosexuals with full blown AIDS in The Netherlands, the number al— ready infected adopts a value between 5,000 and 15,000. The models were also used to predict the long term course of the epidemic. The results indicate that in the absence of prevention HIV infection will be— come endemic in high risk homosexual communities with a prevalence larger than 702. Furthermore an efficacy of e.g. 502 in the reduction of the annual effec- tive contact rate probably has a limited effect; one should aim at a 902 effi- cacy (or more). The mathematical models and the simulation approach are helpful in predicting the impact of intervention measures. MP15 Exposure to the AIDS virus through articifial insemination in a ' population of lesbians in California. CHERI PIES, MSW, MPH; BRENDA ESKENAZI, Ph.D; AMANDA NENSTETTER, MSW.; CHRISTY SHEPARD, R.N. University of California, Berkeley, CA, U.S.A. In 1985, Australian investigators reported that four women who were artifi— cially inseminated tested positive for the AIDS antibody. All four women had received semen from the same donor who was later found to be antibody positive. None of the women had any other risk factors for AIDS. The purpose of the present investigation is to examine in a more comprehensive study the trans— mission of the AIDS virus through artificial insemination. We have chosen to study transmission in lesbian women because lesbians do not, as a rule, engage in heterosexual intercourse and therefore, we could eliminate the contribution of specific sexual practices. In addition, lesbians often select gay men as donors and the incidence of AIDS among the gay population of California is very high. In a pilot study of 48 lesbians in San Francisco, we found that all tested negative for antibody to the AIDS virus. This study was expanded to include lesbians across the state. Each woman who agrees to participate is tested for antibody to the AIDS virus and completes a questionnaire designed to elicit information about her donor insemination history (vaginal vs intrauterine insemination, fresh vs frozen semen, antibody status of donor, health status and sexual orientation of the donor, etc.) and her sexual, health, and repro- ductive history. As of January 1987, 20 lesbians have participated. These women reported obtaining semen from 14 homosexual, 10 heterosexual, and 3 bisexual donors (5 addtional donors were of unknown orientation). One homo- sexual donor has a known positive antibody status and another died of AIDS a year after donating semen. To date, all women have been seronegative. We will report on an update of this study. M276 Low Risk of Anti-HIV Seroconversion in Female Sexual Partners of Haemophlliacs and their Children. E.J. MILLER, R.R. MILLER, E. GOLDMAN, P.D. GRIFFITHS, P.B.A. KERNOFF Departments of Haematology and Virology, Royal Free Hospital, London, UK. The objectives of this study were to quantitate risks of HIV transmission from haemophiliacs to their sexual partners and children; and to identify risk factors for such transmission. A detailed questionnaire was used to assess frequency and modes of sexual contact, contraceptive practice, and other risk factors. The presence of anti—HIV, measured by a competitive ELISA assay, was used as a marker of exposure to the virus. 100 contacts were studied. Contacts of 45 seropositive patients (median period of seropositivity 3 yrs., range 3 mo - 6 yrs) comprised: 30 regular female sexual partners; 21 parents giving clotting factor concentrates to their children; and 10 children aged less than 10 yrs of haemophilic fathers. Contacts of the 28 seronegative patients were similarly distributed. Only one contact was found to be seropositive, giving a 3.3% prevalence rate in the sexual partners of seropositive patients. Risk factor analysis showed nothing to distinguish this couple from other members of the group except that both were abusers of i.v. heroin. Subsequently, however, the man died from zoster pneumonia, the only patient in the study to die from possible HIV related illness. At the time the study started, when all the index patients but few of their sexual partners had been formally counselled, only 23% of the 'seropositive' couples regularly used barrier methods of contraception, compared with 7% in the seropositive group. Following repeated counselling of both partners, the proportion using barrier methods increased, but still remained a minority. All 5 children who must have been conceived at a time when their fathers were seropositive remain well and anti-HIV seronegative. MONDAY, JUNE 1 MR7", Relationship between P.falc1parum malaria and HIV seropositivity at Ndola, Zambia. OSCAR 0. SIMOOYA, R.M. MWENDAPOLE, S. SIZIYA and A.F. FLEMING. Tropical Diseases Research Centre, Ndola, Zambia. One hundred and seventy-two patients presented with symptoms suggestive of malaria in January 1987, at the height of the transmission season. Patients were screened for (i) anti-HIV using the Wellcozyme test, (ii) malaria parasitaemia, and (iii) specific antibodies against P.falciparum using immunofluorescence (IPA) test, significant titres being defined as 1:80 or greater. Two patients with P.malariae have been excluded from analysis. Sixty-seven (39%) of the patients had P.falciparum and 28 (16%) were anti— HIV positive. or the 103 patients without malaria, 20 (19%) were anti-HIV positive compared to only 8 (12%) of those with malaria (X2 = 1.15, p = 0.28). Sixty-three (9h%) of the patients with parasitaemia and 74 (72%) of those without parasitaemia had significant IFA titre. No significant relationships were found in the parasite positive or parasite negative groups between antimalarial IFA and anti-HIV. These data do not support the hypothesis that HIV infection increases the risk of clinical P.falciparum malaria. MID-78 Transmission of Human Immunodeficiency Virus from Hemophiliacs to their Sexual Partners: Role of Parenteral Exposures LYNN SMILEY", c.c. WHITE 11*, c. MACIK‘, P. BECHERER", K.J. wsmnow“, T.J. MATTHEWS“, et al.*University of North Carolina, Chapel Hill and *" Duke University Medical Center, Durham, N.C. To evaluate the risk of transmission of human immunodeficiency virus (HIV) from hemophiliacs to their female sexual partners (SP), 31 infected hemo- philiscs and their SP were studied. One man with 2 SP was counted as two separate couples. HIV infection determined by Western blotting and/or virus isolation was detected in 5 SP (15.6%) of 32 HIV-infected hemophiliacs. Three of the 32 hemophiliacs were intravenous drug abusers (IVDA). The 2 SF of 2 hemophiliac IVDA had HIV infection (1002), whereas the third couple, which included a nonIVDA sexual partner, showed no HIV transmission. Confidential, coded questionnaires were administered to 18 HIV-infected hemophiliacs and their SP. Parameters examined included history of needlestick injuries while the SP assisted in clotting factor treatments, receipt of any transfusions by the SP, intravenous drug abuse, condom usage, oral or anal sex, history of vaginal infections, and monthly frequency of intercourse (since 1981). This cohort excluded any IVDA. Of the 18 SP at risk, there was HIV transmission to three (151). Two of these couples reported no use of condoms. However, the couple which did use condoms regularly reported 8 needlestick injuries. Seven of the 15 uninfected sexual partners of HIV-infected hemophiliacs reported no usage of condoms. There was one reported needlestick injury in one SP in this group. In addition to heterosexual transmission, these data indicate that parenteral exposures are a potentially important risk factor among SP of HIV-infected hemophiliaca. Also shown is the inconsistent use of barrier contraceptives among couples at risk for heterosexual transmission of HIV. "£79 HIV1 and HIVZ infection in a french cohort of homosexual men in r . . , . , . . , . . , MESSIAH and FlfiES-MEDECINS. Eaboratoire de Microbiologie, Hopital Necker, Diagnostics Pasteur, Association AIDES-Paris, France. A cohort has been composed in order to analyse several risks factors in sexual practices among homosexual men in Paris (France). All subjects are consultants of general practitioners and are asymptomatic. They will be follo- wed up for a minimum of three years on clinical, immunological and virological parameters. We present virological results on the first hundred included sub- jects. The sera were tested by ELISA HIV1 and HIV2 (Diagnostics PASTEUR) (DP). All positive results were confirmed by Western Blot analysis HIV1 and HIV2 (DP) : 34 % sera were strongly positive for HIV1, 1 % sera were positive for HIV2 (confirmed by RIPA-HIVZ (Pr. MONTAGNIER)). This subject is malian and has been living in France for ten years. An interesting point is the revelation of only 6 ELISA HIVZ positive sera among the 34 HIV1 positive sera (this raised the question of peculiar cross reaction, or double infection or eventually intermediary virus). Moreover, the detection of HIV1 antigen has been performed by antigen- capture (DP). Only two patients are strongly HIV1 antigen positive (both of them are AB HIV1 positive). The specificity of these two positive results has been confirmed by neutralising reactions. The two subjects are asymptomatic so far and their follow-up will be informative. These two sera were also positive with HIV1 Ag test from ABBOTT Lab. These preliminary results show a low prevalence of HIV2 infection compared to HIV1 but raise the question of the spreading of HIVZ among homosexual men in Paris. 23 M280 Seroepidemiologic evidence of HIVZ infection in Mali and other West African countries and of its heterosexual transmission. JEAN-MARC ALLAIRE+, S. CHAMARET+, S. FERRIS+, M. BARBIER++, A. GINDO+++, L. MONTAGNIER+, et al.,+ Institut Pasteur, Unité d'Oncologie Virale, ++ Hop. International de l'Université de Paris, France,+++ Hop. Gabriel Touré, Bamako, Mali. HIVZ has been isolated recently from AIDS patients and healthy subjects from West Africa. It differs from HIV1 by antigenicity and molecular sequences. Sera from 9 patients hospitalized in Bamako for "slim disease" were screened for HIV] and HIVZ antibodies (Ab) by indirect immunofluorescence (IF) and radioimmunoprecipitation assays (RIPA). One patient, a zairian, was positive for both HIV] and HIVZ, and 3 for HIVZ. One of the latter was hospitalized sub- sequently in Paris presenting with major weight loss, chronic diarrhea, esopha- geal candidiasis and infection with several opportunistic intestinal pathogens; he died a few months later. A study of 43 family members revealed that his wife was healthy but seropositive for HIV2, suggesting that HIVZ can be transmitted heterosexually. A stepmother was also Ab-positive but all other family members including his 3 children were Ab-negative. This evidence of HIVZ infection in Mali prompted a wider study to determine the prevalence of Ab to HIVI and HIVZ in 600 sera selected randomly from West African students living in Paris. All sera were screened by IF ; equivocal results were confirmed by RIPA. To date, screening of 100 sera obtained in 1984 revealed no Ab ; among IOO sera from 1986, one male was positive for HIV] and another for HIVZ. The complete results of these serologic studies will be presented. MR81 Surveillance of Geographic Spread of HIV Infection LYTT I. GARDNER, J.F. BRUNDAGE, R.N. MILLER, D.S. BURKE, J.R. BUNIN Walter Reed Army Institute of msearch, Washington, D.C., 20307 The U.S. HIV epidemic began in a few circumscribed urban centers. We examined the first year of data from screening civilian applicants to U.S. military service to determine geographic spread of infection. A "geographically weighted prevalence" (GNP) was calculated for each county (a function of its first six nmths' crude county prevalence (CCP) and those of contiguous counties). We hypothesized that the GNP would predict subsequent county prevalenoes better than prior CCP alone, if county prevalences are influenced by their neighbors' prevalence. To test this hypothesis, we examined a subset of 48 eastern U.S. counties. Data from these counties revealed the following: For black applicants, the first six nmths' (1:13 vs. second six months' OCP, correlation=0.10 (p=.50); GNP vs. second six months' (ISP, oorrelation=0.41 (p=.005). For white applicants, the first six nonths' OCP vs. second six months' OCP, oorrelation=0.20 (p=.17); GNP vs. second six mnths' GDP, correlation=0.34 (p=.02). The hypothesis of geographic spread fran high prevalence areas into low prevalence areas is supported strongly for the black applicant population, but less convincingly for the white applicant population. Maps of the eastern U.S. displaying Me for the first, second and third six moth periods, and Gill’s, reinforce statistical criteria on which the conclusions are based. M282 Lifzsmission of HIV to partners of Seropositive Heterosexuals from r co. H.TAELMAN, WUX, P.CORNET, G.von der GROEN, P.PIOT. Institute of Tropi- cal fiedicine, Antwerp,Belgium; Medical Center, Ministry of Foreign Affairs, Brussels, Belgium. Heterosexual transmission of HIV among individuals originating from or having resided for prolonged period of time in Africa was evaluated. Thirty-eight spouses and/or regular partners of 35 HIV-seropositive hetero- sexual males (18 Afr.,17 Eur.) and 10 spouses and/or regular partners of 10 HIV-seropositive heterosexual females (9 Afr.,1 Eur.) were tested for HIV- ontibodies using ELISA and IF or Western-blot methods. All the spouses and partners had their medical history including sex life habits recorded and had 0 physical examination. Overall seropositivity among the female partners was 73% (28/38) and 40% (4/10) among the mole partners. HIV cultures carried out in 7 male and 6 female seronegative partners were positive in 3 and 2 respectively. Overall HIV infection rate was thus 81% among the female partners and 60% among the mole partners. 0f the female partners, 3 had a history of promiscuous heterosexual activity, 6 had 5 than 5 partners, and 29 were monogamous with no other risk than heterosexual activity. Evidence for female to male transmission was obtained by primoinfection in 2 cases, monogamy in 1 case and by positive HIV culture in o seronegotive mole who had recent sexual contacts with o sero- posiilve female. Our data suggest that to be the spouse or the regular partner of an infected heterosexual individual is a major risk factor for acquiring HIV infection. HIV transmission rate in this study was significantly higher than rates found in the group of heterosexual hemophiliccsand transfusion recipients. MONDAY, JUNE 1 Mesa HIV Infection in Sexually Active Heterosexual Adults Attending a New York City STD Clinic. ALAN K. LIFSON**, R.L. STONEBURNER*, M.A. CHIASSON*, D.S. HILDEBRANDT*, S. SCHULTZ*, H.N. JAFFE.** *New York City Department of Health, New York, NY; **AIDS Program, Centers for Disease Control, Atlanta, Georgia To evaluate heterosexual transmission of HIV among sexually active persons, patients attending a sexually transmitted disease (STD) clinic in New York City were enrolled in an ongoing case-control study that included serologic testing for HIV antibody, hepatitis B, and syphilis and an interview about sexual practices and known risk factors for HIV infection. From December I, 1986, through January 21, 1987, 64 men and 25 women were enrolled (72% black, 132 Hispanic and 12% white; median age = 27 yrs; current enrollment = 60-80 patients/month). Antibody to HIV was present in 2 of 4 homosexual men, 5 of 11 bisexual men, and 6 of 9 heterosexual intravenous drug abusers (IVDA). None of 65 heterosexual non-IVDA had HIV antibody, including 10 persons (5 women and 5 men) who had sexual contact with an IVDA. The remaining 55 heterosexual non-IVDA had a median of 15 different sexual partners since 1978; 41 (75%) had a history of at least 1 previous STD, 16 (29%) had engaged in rectal intercourse, 36 (65%) never or rarely used condoms, and 15/38 (392) men reported sexual contact with a female prostitute. In the city with the Largest number of heterosexual AIDS patients in the United States, these preliminary results suggest a low prevalence of HIV infection among sexually active heterosexual adults who are not IVDA. M284 Human Immunodeficiency Virus Infection in Patients with Hepatitis B. Virus and Hepatitis Delta Virus Infections in Los Angeles, 1977-1985. KEVIN M. DE COCKl J.C. NILAND, H.P. LU, V. EDWARDS, C. SHRIVER, J.H. MOSLEY, et. a1. University of Southern California School of Medicine, Los Angeles, CA. Stored sera from 723 patients with acute and 228 with chronic hepatitis B seen in Los Angeles between 1977 and 1985 were tested for antibody to human immunodeficiency virus (anti-HIV). We first detected anti-HIV in homosexual men in 1979 and in intravenous (iv) drug users In 1981. For acute hepatitis B, the seroprevalsnce of anti-HIV in homosexuals ranged from 14—33%, with no significant change from 1980-1985; seroprevalence rates in heterosexuals, including iv drug users, remained under 51. Age stratified prevalence rates were higher in homosexuals and iv drug users with chronic than with acute hepatitis, and in homosexuals compared to non—homosexual subjects. In chronic hepatitis B. anti—HIV seroprevalence reached 501 in homosexual men in 1983 and 301 in iv drug users in 1985. A significant association existed between infection with HIV and hepatitis delta virus in homosexual men but not in iv drug users. Anti—HIV seroconversion rates in homosexuals with chronic hepatitis B were 221 in 1963 and 81 in 1985. Increased frequency of HIV infection in chronic hepatitis B probably reflects more extensive exposure. Our findings suggest that HIV transmission has reduced in recent years in homosexual men, in whom delta hepatitis and HIV infection share common risk factors. MP85 HIV Screening in the High Risk Obstetric Population and Infant Sero- ' logic Analysis JOHN P. JOHNSON*, L. ALGER, P. NAIR, S. WATKINS, K. JETT, S. ALEXANDER; University of Maryland School of Medicine, Dept. of Pediatrics and the Dept. of Obstetrics, Baltimore, MD. and Biotech Research Laboratories, Rockville, MD. Voluntary screening by a commercially available Enzyme Linked Immunoabsorbant Assay (ELISA) for seropositivity to Human Immunodeficiency Virus (HIV) was conducted in an inner city obstetric population over a six month period. Of one hundred fifteen women who identified themselves to be at risk for HIV in- fection and consented to testing, thirty-four, i.e., 29%, were confirmed sero— positive. Most of the women (90%) had used intravenous drugs, the remainder were sexual partners of IV drug users. Ten children born to these women have been followed for six months orgreaEr. Of these, five children can be demonstrated to be endogenous seropositives: Western Blot analysis revealed two children who developed IgM against gpAl or p55 by A months of age and one child who developed new IgG bands against p55 and p66 at three months of age. Standard ELISA testing documented two child— ren who lost and then reacquired seropositivity by nine months of age. Three of the five children with serologic evidence of infection have clini— cal disease: one has marked lymphadenopathy, one has AIDS Related Complex and one has AIDS. The two children who developed IgM against HIV show' nosymptoms. Neonatal serologic analysis of antibody to HIV has allowed identification of those infants producing endogenous antibody, thereby permitting earlier diagnosis and treatment of infected children. These results support earlier evidence for approximately 50% perinatal transmission rate. The possibility that early IgM synthesis against HIV may reduce the development of clinical disease is suggested. 24 Mass Natural History of Immune Function in HIV Infected Hemophiliacs. QQHN L; SULLIVAN, D.B. BRETTLER, R.A. SCHORR, S.M. BAKER, D.L. WILLITTS, P.H. LEVINE, University of Mass. Medical Ctr. and Worcester Memorial Hospital, Worcester, Massachusetts, USA. As part of a prospective study of immune function following human immunodeficiency virus (HIV) infection in hemophiliacs. 93 hemophiliacs (9 seronegative, ll seroconverters and 72 seropositive) have been followed over a 4 year period. MEAN DATA FROM A YEAR OF STUDY SEROPOSITIVE AND SERONEGATIVE HEMPHILIACS sag l flfi Year Year Year 4 T helper PWM T helper PWH T helper PWM T helper PHM Normal Controls 30 928 10 995 100 972 100 1010 100 Seronegatives 9 1228 78 114:1 88 1065 72 1062 88 Seroconverters 11 95b 52 Eh9 5k 670 24 #15 #5 Seropositives 72 7&0 #5 727 AA 589 1+0 519 38 *=ceIIs/ul;**=%control counts per minute Seroconversion in 11 of 93 occurred between year 1 and 2 of the study. HIV infected individuals have shown a progressive decline in T helper cell numbers and function as measured by pokeweed mitogen stimulation. Recent seroconversion (within 2 years) following HIV infection is associated with significant (p<.05) loss of T helper cells. One-third (332) of our total seropositive hemophiliac population has shown progressive decline of T helper cells to AOO/ul or less during a maximal exposure period of 4-7 years. These data strongly support a high rate of progressive immunologic attrition in HIV infected hemophiliacs. MP87 Serum HIV Antigen (HIV—Ag) as a Predictor of Progression to AIDS and ARC in Homosexual Men DENNIS OSMOND*, R. CHAISSON*, M. LEUTHER**, JP ALLAIN**, AR. MOSS*, *UCSF, San Francisco, CA, and **Abbott Laboratories, USA To test the presence of serum HIV—Ag as a predictor of subsequent disease, we studied 30 initially healthy anti-HIV seropositive homosexual men undergoing prospective study for two years. Ten subjects had less than 400/mm3 T-helper cells at entry or at followup (Group 1). Ten subjects had greater than 600/mm3 T—helper cells at baseline and at followup (Group 2); and ten subjects had less than 600/mm3 T-helper cells at baseline but had a net gain of 200 T-helper cells at followup (Group 3). HIV—Ag was detected in sera using the Abbott sand- wich enzyme immunoassay for HIV p24. HIV—Ag was present in 6 subjects, all in Group 1. 6 of 6 HIV—Ag positive subjects developed ARC and 4 subsequently dev- eloped AIDS. 1 subject (from Group 3) of 24 HIV—Ag negative subjects developed ARC (p<0.0001). The remaining 23 subjects remained healthy for the entire period of the study. 4 of the 6 with Ag positive specimens were positive at baseline and followup (3 AIDS, 1 ARC); 1 at baseline only (AIDS); and 1 at followup only (ARC). The A subjects developing AIDS were diagnosed from 26 to 32 months after the first HIV—Ag positive serum specimen. The presence of HIV antigen in serum, as detected by this assay, is highly predictive of develop— ment of ARC or AIDS, and may be detected up to 32 months prior to progression. Supported by a grant from the Universitywide Task Force on AIDS. M388 Association of Donor Characteristics with Transmission of HIV f Infection to Recipients JOYCE C. NILAND*, THE TRANSFUSION SAFETY STUDY GROUP* **, *USC School of Medi- cine, Los Angeles, CA, **other participating institutions. By testing sera stored prior to the availability of routine anti-HIV screen- ing, a national, multicenter study has identified 91 recipients transfused with anti-HIV(+) components. Among these 81 (89%) are anti-HIV(+) and 10 (11%) are anti—HIV(-). In 15 instances, 2 recipients in the study received blood from the same donor. In 13 pairs, both recipients are anti-HIV(+). In 1 case, one of the recipients became anti-HIV(+) and the other is anti-HIV(-); the donor was a 19 yr. old male. In the last pair, both recipients are anti— HIV(—); the donor was a 26 yr. old bisexual male. In comparing characteristics of donors who transmitted infection (Group I) to those who did not (Group 11), similar sex and age distributions were seen. Groups I and II also had similar mean enzyme immunoassay (EIA) absorbences (0.99 vs 1.16, NS) and ranges. Group II had higher percentages with P150 (29% vs 5%, p=.10) and P120 (43% vs 17%, p=.12) on lnmunoblot (13). All donors had GP41 and P25 on radioimmunoprecipitation (RIP) and P24 on IE, and all but 3 donors in Group I had P41 on 13. A somewhat greater percent of Group I donors came from a high AIDS risk area (53% vs 29%, NS). Among 25 Group I and 5 Group II donors enrolled for further followup, 79% and 60% respectively are homosex- ual or bisexual males. 93% of the Group I donors are free from clinical signs of AIDS 1-2 yrs. post—donation, although 63% have T4/T8 ratios < 1. Thus, no clear relationship between the characteristics of the donor and transmission of HIV infection to the recipient can be seen. (Supported by Contract N05. N01- HB-4-7002 and N01-HB-4-7003 of the National Heart, Lung and Blood Institute.) MONDAY, JUNE 1 ““289 HIV TranSMission Among Homosexual Male Partners EVidence of the Inefficiency of TransmisSion GEQB§§”8;_§§A§§_LLLA. A. HARDYAA. K. MAYERAA‘. J GROOPMAN’U"UK A. BARRY*. G, LAMB4. et al.. *Boston Department of Health and Hospitals. Boston. Ma. A”‘Centers for Disease Control. Atlanta Ga. ‘**Fenway Community Health Center. Boston. Ma. acaANew England Deaconess Hospital. Boston. Ma To evaluate the rates of transmiSSion of HIV among homosexual couples, we studied 158 sexual partners of people with AIDS. ARC and HIV seropOSitive and seronegative healthy men. HIV seropos1tivity rates for partners of AIDS were 02% (1b/26L partners of ARC were 40% (13/34). partners of healthy seropoSitive were 45% (13/29). and partners of healthy seronegatives were 20% (14/69L 0f the 158 pairs. 63 (40%) were concordant seronegatives were concordant seropositives (27%). and 53 (33%) were discordant. Virus isolations were attempted on each partner of the discordant pairs. and an isolation rate of 0% among the negative partners and 21% among the positive partners was found None of the 3b discordant pairs that have returned for their six month follow—up vis1t.have become infected. This is of interest because 27 (75%) of the seronegative partners had engaged in unprotected sexual actiVities ((28% receptive analL (72% receptive orall] with their infected partner during this time period. These results indicate that there may be additional nonbehaVioral factors related to HIV transmisSion and susceptability 42 MP9“ Prospective Immunologic Study of Intravenous Drug Abusers (IVDA) ' Enrolled in a Methadone Program. CHRISTINE A. NSILDO, M.H. GRIECO, E.J. GINDI, D.K. BROWN, M.M. REDDY, E.B. KLEIN, St. Luke's7Rooseve1t Hospital Center, New York, N.Y. 173 patients with IVDA had baseline evaluations from September, 1964 to April, 1986 in a study designed to examine parameters associated with serum antibody to HIV and predictive of conversion to ARC and AIDS. 53 patients or 31% had antibodies to HIV by ELISA with confirmation by Western Blot, performed by c.w. Saxinger and S.H. Weiss at the NCI. The following mean laboratory parameters were statistically different (p(.0.01) between HIV-negative and —positive patients: (1) CDT4/CDT ratio, 1.50 vs. 0.90, (2) CIq 30.2 vs. 56.5 ug/ml, (3) beta-2 M, 2595 vs. 3363 ug/l, (4) absolute lynphocyte count 2578 vs. 1856/cmm, (5) % CDT4, 34 vs. 27, (6) absolute T4 894 vs. 492/onn, (7) % CDT 25 vs. 33, (8) absolute T 1436 vs. 1014/cnm, respectively. Total interfegon titers (p( 0.05) of negative vs. positive mean values were 1:8.8 vs. 1:23. None of the 53 HIV-positive patients had AIDS on initial evaluation but 16 (30%) had LAS. In the HIV-positive subjects, beta-2 M was increased above 2500 in 37, and the absolute T count below 500 in 30. Interferon level was elevated above 1:16 in 9. During the subsequent year, 5 patients developed AIDS and a 6th developed severe recurrent bacterial pneumonias. All 6 of these subjects were characterized by elevated beta-2 M (mean 4259) interferon (mean 107) and low absolute T4 counts (mean 203). In this cohort of HIV positive subjects, 9.4% prospectively developed AIDS within 1 year. All had elevated beta—2M and interferon levels and absolute T4 count averaging 203/cmm. MR91 Female to male heterosexual transmission of HIV infection in Nairobi D WILLIAM CAMERON**, FA PLUMMER**, JN SIMONSEN**, J0 NDINYA-ACHOLA*, LJ D'COSTA*, P PIOT*** et al. *Univ Nairobi, Kenya Medical Research Center, Nairobi City Commission, Nairobi, **Univ Manitoba, Winnipeg, *** Institute of Tropical Medicine, Antwerp. HIV is apparently transmitted with greater ease via heterosexual intercourse in Africa than in other regions. Concomitant STD's particularly genital ulcer disease (GUD) has been postulated as one co—factor which might facilitate sexu— al transmission. In order to quantitate the risk of HIV acquisition by a man after a single exposure to an infected woman and to determine if GUD increased the risk of HIV transmission we are conducting a prospective study of men who acquire an STD from a group of prostitutes with a known high prevalence of HIV infection ( >85 Z, HIV+). All men presenting to our clinic with an STD who reported one of these prostitutes as a source contact were enrolled in the study. 277 men have been enrolled in the study of which 9 Z were initially HIV+. The major risk factor for HIV+ was a past history of GUD. Number of lifetime sex partners, frequency of prostitute contact, number of injections, blood transfusions and a past history of urethritis did not correlate with HIV+. 130 seronegative men have been followed for a mean of over two months. Seroconversion to HIV occurred in 6/54 men with chancroid, 3/69 men with ure- thritis and 0/7 men with other diagnoses (p = NS). Overall HIV seroconversion has occurred in 9/130 or 7 Z of exosed men. The risk of HIV transmission from an HIV-infected prostitute to a male sex partner is substantial and may be facilitated by GUD. 25 M292 Relationships Between Decline in CD4 Lymphocytes and Other Variables Among 1828 Seropositive Gay Men. A Munoz, V Carey, BF Polk, A Saah, J Phair, L Kingsley, J Fahey, for the flu ticenter AIDS Cohort Study (MACS), NIH, Bethesda, MD.I USA Longitudinal data were available at 4 visits six months apart. In order to relate the decline in CD4 cells to changes in other variables over time and to levels of variables available only at entry, we used an autoregressive model in which one relates CD4 cell number to covariates, conditioning on previous number of CD4 cells. In the final multivariate model. the following variables were significant predictors of subsequent number of CD4 cells after controlling for previous number of CD4 cells: C08 cells, platelets, serum IgA, hemoglobin and HIV anti- body level. To measure the magnitude of the predictive power of these significant variables, we compared the subsequent numbers of 004 cells of two individuals who differed by approximately one standard deviation in a given covariate but were identical otherwise (including the prior number of CD4 cells). The percentage reductions of CD4 cells associated with differences in a given covariate were as follows: % fewer CD4 cells Difference in covariate .8. 1.5 times t e num er 0 8 re ls 3.7% decrement of 50,000 platelets 1.7% decrement of 1.0 gm% of hemoglobin 1.4% 2.0 times the IgA level 1.4% decrement of 0.5 in OD of HIV antibody These data suggest that several covariates in addition to previous number of CD4 cells have significant predictive power for estimating the decline in CD4 cells in HIV seropositive subjects. MP93 HIV-seroconversion in a Cohort of Homosexual Men in Stockholm be- tween 1983 and 1986. GDRAN BRATT, A KARLSSDN, G v KRUGH, L MDBERG, G BIBERFELD, E SANDSTRUM. Venhal— san, deersjukhuset, Stockholm. Immunological Dept., National Bacteriological Laboratory, Stockholm, Sweden. Since Nov 1982, a clinic in Stockholm with gay staff has offered healthy gay men venereological screening. A consecutive serie of 166 men who first attended in Feb-May 1983 has been followed at yearly intervals. Examinations included HIV-serology, T—lymphocyte subsets and serum-electrophoresis. Results: In 1983 HIV-antibodies were found in 31/166 (18. %). In 1984 10 (8.0%) of the 125 previously negative men who returned had seroconverted. A further 4 (4.0%) had seroconverted in 1985 when 101 previously negative men re- turned, and of the 85 previously negative men who returned in 1986 5 (5. %) had seroconverted. The T—lymphocyte subsets and 190 levels before (0) and at the first (1), second (2) and third (3) year after seroconversion were as follows: 0 1 3 T4 (x109/1) 0.97 1 0.38 0.69 :_0.27 0.60 I 0.24 0.59 1 0.26 18 (x109/l) 0.81 1 0.42 1.00 1 0.49 0.88 1 0.37 0.79 i 0.22 T4:TB 1.3 1 0.2 0.7 I 0.2 0.7 I 0.2 0.7 : 0.2 190 (g/l) 11.7 i 2.3 12.9 1 2.6 13.9 1 2.7 14.0 1 1.5 Conclusion: HIV-seroconversion is still seen in this prospectively followed co—hort in spite of decreasing risk factors. The implications of this will be discussed. Early after seroconversion there was a fall to a persistent low level of T4 lymphocytes and a transitory increase in T8 lymphocytes. IgG in- creased progressively during the follow up. MBg‘ MW Sara to Human Imunodeficiency Virus (HIV) and Simian T-Lymphotropic Virus III (STLV-III). JULIUS A.A. MINGLE". M. HAYAMI ' , n. oer-KwASI“, r. ISHIKAHA , A.R. NEEQUAYE', v. rarity“ ‘, at.a1. *Univezsity of Ghana Medical chgoi, Accra, Noguchi Memorial Institute for Medical Research, Legon, Accra Institute of Medical Science, University of Tokyo, " 'St. Joseph Hospital, Koforidua, Ghana. Acquired immunodeficiency syndrome (AIDS) in Africa which was previously confined to the East and Central African countries Is now in West Africa. The disease In Africa may take an epidemic character it measures are not taken to check its spread. Prevalence rates and the risk groups therefore need to be assessed and identified. Detection of antibodies (Abs.) to HIV and STLV-III antigens (Age.) was carried out in human ser- from blood donors, prostitutes, sickle cell disease patients and others. The ELISA and Immunofluorescence (IF) techniques were used for HIV Ags. and IF for STLV—III. Out of a total of 997 samples (226 from prostitutes) examined for HIV and 737 for STLV-III. Abs. 93 including 57 prostitutes were positive for HIV and 18 for STLV-III Abs. Some of the sera reacted better to STLV-III Ags. Western blotting test also confirmed these differences. Reports on Senegalese showed that some reacted to STLV-III Agl. without any disease. The Ghanaienl reacting to STLV-III showed disease. The Western blotting reaction suggests that some a! the Ghanaian: have been exposed to a virus which may be closely related to STLV—III. A new virus HTLV-IV has been reported from Senegal. Retrovirul infection in Africa mly therefore be more varied than In the western Hemisphere. Isolation and characterization of local strains of HIV and their inclusion in tests II Age. may be necessary to determine the incidence rates in some of there African countries. Vork is currently going on in this direction. MONDAY, JUNE 1 Mngs Concomitant HTLV-I and HTLV-lll Infections - A Serological Survey ‘ in Washington, D. C. Area KENNETH s. CHANG*, LAI-CHE WANG’, STEVE ALEXANDER“, T. LOG***, A. F. KUO*'* m*", et al., *Laboratory of Cellular Oncology, National Cancer Institute, “Biotech Research Laboratories, Inc., *"Commission of Public Health, District of Columbia A serological survey for the presence of antibody against HTLV-I and HTLV- III (HIV) was conducted on serum samples collected in 1984 from four groups of individuals: (A) VDRI. (-) premarital individuals (n=113), (B) senile, chronic disease patients in D. C. Village Hospital (n=155),‘ (C) drug abusers (n=151), and (D) male homosexuals (n=187). ELISA positive sera were titrated and fur- ther examined by immunofluorescence and Western blot tests. ELISA tests using goat antihuman (IgA, IgG, IgM) serum were more sensitive than those using goat antihnman IgG serum. HTLV-I antibody positive rates for these groups were: (A) 5.3%, (B) 9.0%, (C) 18.5%, and (D) 4.3%. HTLV-III antibody positive rates for these groups were: (A) 0.9%, (B) 4.5%, (C) 10.6%, and (D) 4.8%. The majority of individuals with positive tests were either reacting against HTLV-I or HTLV-III only. However, some individuals who belonged to groups C and D showed antibodies reacting against both viruses. These were confirmed by Western blot tests in which p19, p24, and env antigens of HTLV-I as well as pl7, p24, p41, and gpIGO antigens of HTLV-III-fire reactive with these sera. These preliminary results suggest the possible occurrence of concomitant infection in these individuals with both HTLV-I and HTLV-III, although other possibilities such as past se- quential infections, and presence of cross reacting antibodies against viral or cellular antigens can not be excluded. Mega Epidemiology of HIV Infection in Martinique, French Department in the West Indies. NICOLE MONPLAISIR',C.NEISSON—VERNANT",G.SOBESKY‘*,I.VALETTE',R.DEMEULEMEES- TER‘“*, 4'Centre de Transfusion de Martinique, *‘Centre Hospitalier Regional de Martinique, “'Inspection de la Santé, Paw de France, Martinique. Since August 1985, 15207 blood donations from volonteer blood donors and 1399 high-risk people were tested using "ELAVIA" first generation assay. Positive specimen was retested by Indirect Immunofluorescence on fixed cells and confir- med with Western Blot (Pasteur) and Recombinant Env/Core protein assay (Abbott) All confirmed seropositive people were clinically evaluated and assessed for blood cell count, T Lymphocyte numbers and ratios, serum immunoglobulin and fieta 2-immunoglobulin levels, TPHA and Hepatitis B serologicals status and cu— taneous multipuncture tests (Merieux). Blood donors were compared to heathly controls. 0,2 5 of blood donors and 6 Z of patients were positive whose 15 with AIDS. In blood donors. among 83 repro- ductible Elavia test. 23 were Western Blot negative and 30 uninterpretable. Are they seroconversion or due to other retrovirus ? Recombinant proteins assay agree with Western Blot. In 50 Z of the donors, no usual risk factors have been founded, but hetero- sexual transmision could been involved. 70 X of the subjects had histories of S.T.D. 50 X of HIV positive, non—AIDS people are clinically asymptomatic, but have biological abnormalities. The average of T Helper cells is significantly higher for controls than for HIV positive. The epidemiological caracteristics seems to be intermediary between those existing in France and the United States on one hand and Haiti and Africa on the other (heterosexual contamination and sex-ratio). M297 Synthetic env- and gag- Peptides Are Recognized by HIV-specific Antibodies R.V. PETRUV, RAKHIM M. KHAIIUV, L.A. FONINA, A.L. LIUZNER. 1.8. SIDUROVICH, S.M. ANDREEV, Institute of Immunology, USSR Ministry of Public Health, Moscow, USSR. First generation of HIV-antibody diagnostic kits may be biohazardous and re- quire verification due to strong immunochemical heterogeneity of the test sys- tems. In order to solve these problems we synthesized peptide antigenic deter- minants specific for the products of "env" and ”gag” HIV gene expression and produced monoclonal antibodies against some epitopes of HIV structural proteins Env- and gag-specific structures were recognized among the produced spectrum of peptides with the help of commercial sera which gave the extinctions comparable with those obtained with the whole virus particles on polysterene. Immunizing splenocyte cultures in vitro by whole immobilized virus or by the synthetic peptides we obtained HIV-specific monoclonals. We are studying the possibility of producing ELISA systems on the basis of "peptide—monoclonal Ab" pairs to be used instead of the complicated systems of the First generation which require immunoblntting with whole virus proteins. 26 Cutaneous and plasmatlc Von Wlllebrand factor In AIDS : a marker of endothelial stimulation ? MICHEL JANIER', B. FLAGEUL‘, L. DROUET**, M.L. SCROBOHACI", A. PALANGIE", F. COTTENOT", * Department of Dermatology, '* Department of Hemostasls, Hopltal Saint-Louis, Paris, France. Patients Infected by the human Immune deficiency virus (HIV) (lymphadenopathy syndrome (LAS), Kaposi's sarcoma (KS), opportunistic infection (on) represent a model In which endothellal stimulation is Important. We studled plasmatlc values of Von Willebrand factor (VWF) as an indicator of endothelial stimulation in us LAS, 23 AIDS KS and 9 AIDS OI In comparison with 19 normal controls and 12 classical KS. VWF was found to be elevated in AIDS OI (P < 10-7) and AIDS KS (P < 10") and at a lesser extent In classical KS (P < 10—3) and LAS (P < 10'2). No correlation was found between plasmatic VWF and a number of clinical and biological parameters : inflammation, Immunological status, age, tumoral Burden, renal and hepatic functions. This elevation seems more to be linked to symptomatic or asymptomatic Infections than to the KS itself. To ascertain the diffuse vascular proliferatlon In these situations, we studied the number of vessels within the superficial dermis of clinically uninvolved skin by an indirect lmmunoperoxidase method using an antlbody directed against VWF in 20 LAS 8 10 AIDS K5 in comparison lo 11 controls and 10 classical KS. An Increase in the number of vessels was found in LAS (p <0.01), AIDS KS (p<0.01) and classical KS (pin'leymphocytes. Decreased B—csll ecto— S'NUC was correlated to reduced proliferation after in vitro stimulation or mononuclear cells with mito- and sntigenes. In conclusion: in patients with antibodies against HIV, decreased ecto-S’NUC activity in B-lymphocytes is correlated to the immunodeficiency, whereas AIDS patients with severe immunodeficiency ofteh had normal activity in Tecells. MP114 'Ihe Frequency and Gnracterization of Oligoclonal Protein (OCP) ' Bands in Individuals with HIV Antibodies MIRKA DEHSCH, M.A. Brom, C.F. lbpetti, Anerican Medical Laboratories, Fairfax, VA [SA Sera iron 20 adults with I-EEV antibodies were selected for determination of the incidence and isotype of oligoclonal proteins (OCP), and the relationship of these bands to serun concentrations of IgG, A, IgM, C3 and C4. HIV antibodies were ease with ELISA and Western ot. ocp were characterized by annunofixation with H or L chain—specific antisera. Protein giantitation was performed with rate nephelanetry. OCPs were found in 13/20 (65%) of anti—HIV reactive sera. ‘lhese (XIPs vere: 6.x (3 samples); G,L (3 saw es); G,K and G,L (6 samples); and K and L without an identifiable H c in (1 5 le). lb 19A or 1934 cops were evident. The nean [IgG] for the 0CP+ sera was Significantly elevated (see Table) in congarison to both the reference range and the mean [IgG] for the (L‘P- sera. Mean serun levels of IgA and IgM were similar for both ocr+ and OCP— samples. There were, however, 9/20 individual sera with elevated IgA (332—929 ng/dl) and 5/20 sera with elevated IgM (387-595 ng/dl). DEVertheless, the increased levels of these isotypes were strictly polyclonal in d1aracter. The [C3] and [C4] for most sanples were within the reference ranges. lb striking differences in ocmplanent levels were associated with presence of oligoclonal bands or with elevated inmmoglobulins. mg/dl: G A M C3 C4 Ref Range 540-1380 70-312 56-352 83-177 15-45 ocr(+) 2896: 495 289: 55 266: 45 1101 11 271 5 ocp(—) 1632: 236 427: 91 217: 55 112: 3 311 4 p50CP + to - 0.0344 0.1856 0.5079 0.9179 0.6503 \ ““2115 ANTICARDIOLIPIN ANTIBODY, NEUROLOGIC COMPLICATIONS AND HIV INFECTION RI. Brey*, RW Houk*, TM Duginski*, PJ Patel**, Wilford Hall Medical Center, San Antonio, TX*, Meharry University, Nashville, TN** Serologic evidence of antibodies directed against cardiolipin (ACLA), one of many antiphospholipid antibodies, have been associated with thromboembolism, recurrent abortion and a variety of neurologic disease. Lupus inhibitors, also antiphospholipid antibodies, have been described in patients infected with HIV and opportunistic infection. We measured ACLA IgG by an enzyme—linked immunosorbant assay in 11 patients with HIV infection and either neurologic abnormalities, thromboembolism or recurrent abortion. Normal values were established in our laboratory. Raw data was transformed into a binding index (BI) by the method of Loizou (Clin exp Immunol (1985) 62,738-745). A positive value is defined as BI > 3 standard deviations above the mean (0.86 +/— 3(.58) = 2.6). Only 2 patients had immune deficiency and none had opportunistic infection. All but 1 patient had abnormal ACLA IgG values. The clinical syndromes represented are as follows: thrombosis in l, recurrent abortions in l, headaches in 3, neuropsychiatric symptoms in 4, herpes zoster in l, peri- pheral neuropathy in 1. ACLA 136 value in this last patient was normal prior to the development of his neuropathy, but became abnormal 4 months after his symptoms began. These observations demonstrate that antiphospholipid anti- bodies are not limited only to patients infected with HIV and opportunistic organisms. A relationship between these antibodies and neurologic symptoms in HIV infection is suggested. 29 ““2116 The Biopsychosocial Research Center on AIDS: A Multidisciplinary Ap— proach to the Investigation of the AIDS Disease. CARL EISDORFER, J. SZAPOCZNIK, G. SCOTT, M. FLETCHER, N. KLIMAS, M. FORDYCE- BAUM, et a1., University of Miami School of Medicine, Miami, FL. Seven major studies are currently being conducted at the center. The objec- tive of this research is to conduct a multidisciplinary, longitudinal study of the AIDS disease which examines several HIV positive groups from a psychoneuro- » immunological perspective. The center is organized so that common strategies, procedures and data are utilized by all studies. Similarly, a thematic empha- sis is shared by all center components; factors are examined that influence the transmission of disease, mediate the likelihood of increased pathology, and in— fluence the course of infection. The studies focus on: the psychosocial co-factors and cognitive AIDS-related dementia in an HIV positive, homosexual population; the neurological aspects of pediatric HIV infection; predisposing factors, course and rate of deterioration following HIV exposure in a population of I.V. drug abusers; the effect of an exercise intervention in a population of HIV. positive and negative gay men; an intervention study which examines the prevalence and specific risk factors asso— ciated with the presence of antibodies to the virus in both HIV positive and negative I.V. drug abusers; the role of nutritional factors in the development of AIDS in an HIV positive population; and, attitudes toward AIDS and health core practices among aHaitian population. Variable assessment is extensive and wide-ranging. Preliminary data will be presented from each study. MR117 EBV and HIV Antibodies in Broncho—Alveolar Lavage (BAL) and in Serum of HIV Positive Children with or without Pulmonary Lymphoid Hyperpla sis/Lymphoid Interstitial Pneumonitis(PHI/LIP)Complex. A Causal Association ? L.BOCCON-GIEOD‘, A.GRIMTELD*’, A.SARDET**, S. BARUCHEL*", G.de THE"*’. Depart ment of 'Pathology, “*Pediatric Pneumology and ”'Pediatrica, Hapital TROUSSEAU Paris, "*‘CNRS Laboratory, Faculté Alexia Carrel, Lyon, France. The PLH/LIP complex is a common finding in children with AIDS. The role of EBV activation in determination of LIP has been recently suggested. To assess the profile of EBV and HIV antibodies in HIV-positive children pre- senting with pulmonary pathology, we investigated BAL in 27 consecutive pati- ents. Out of those,for the last 13, we titered antibodies to HIV and EBV by im- munofluorescence, both in serum and BAL. From the clinical view point, 5 had PLH/LIP complex, 3 Pneumocyetis carinii (PC), 2 other opportunistic infections (OI) and 3 had ARC. 4/5 of LIP cases had serum EBV profile suggesting viral ac— tivation (IgG EA : high titers, IgA VCA : traces). 1/5 had normal EBV immunity. In BAL, IgG VCA were detected in 3/5 LIP. In the 5 LIP cases, HIV antibody ti— ters were significantly higher than in non—LIP patients (p‘(0,001). In the 8 non—LIP children, 6 (3 ARC , 2 GI, 1 PC) had no EBV antibodies at all, 1 had a profile of recent infection, 1 normal immunity. The CDN/CDS ratio in BAL (mono- clonal antibodies staining, immunoperoxydase technic) was very low in all HIV positive children , regardless to pulmonary pathology : 0,20 t 0,11 as compared to 0.87 1 0,15 in normal children (p<:0,001) but the absolute number of CD8 cells recovered by BAL was very significantly higher in LIP patients. In pulmo- nary biopsies of LIP cases, we observed large predominance of CD8 lymphocytes with very few B lymphocytes. EBV activation may represent a critical cofactor enhancing both CD8 lymphoid pulmonary infiltration and HIV replication in children with PLH/LIP complex. MR118 Leu7 (HNK—l) Cells In AIDS And Related Syndromes C.AMIEL, T.MAY, M.C.BENE, G.FAURE, P.CANTON. Maladies Infectieuses and Lab. Immunology. CHU de Nancy Vandoeuvre les Nancy. FRANCE. Leu7 (HNK—1) is a monoclonal antibody initially described as specific of human natural killer cells. Previous reports have related elevations of the lymphocyte subset defined by this marker to viral infections. we investigated this specific subset, in comparison with classical T—cell markers (CD3, CD4, CD8), in a population of 151 HIV—seropositive patients. AIDS was diagnosed upon clinical examination in 26 of these patients.A total number of 235 analyses was performed, using classical indirect immunofluorescence techniques on peripheral lymphocytes isolated by Ficoll gradient centrifugation. Percentages and absolute numbers of each subset were plotted and compared. Classical profiles were obtained for CD3 and CD4, significantly lower in AIDS patients. The mean percentage and absolute number of Leu7+ cells was increased in non—AIDS seropositive patients, compared to normal controls (Sespectively 20.3% — 303 cells/mm3 and 10% — 255 cells/mm ) In AIDS patients, the percentage of Leu7+ cells remained elevated, while their number was significantly lowered. No significant correlation was obser— ved between this subset and the CD8+ subset. In conclusion, our data indicate the participation of a lymphocyte subset involved in anti—viral mechanisms in the early stages of HIV infection. MONDAY, JUNE 1 M2119 Characterization of the latent period and the development of neutralizing antibodies in early sexually transmitted HIV Infection. ANNAMARI mum“; J. ANTONEN i“, s. VALLE***. J—P. ALLAIN ****, K.J.E. macaw." , *cha‘ NCI. Bethesda, MD, ** Inst.Blomed.Sci., Univ.Tampere. Finland. ** private practice. Helsinki,Finland and ****Abeott Lab.. North Chicago. IL. we have prospectively followed immunological and virological events in 15 Finnish men who contracted HIV infection through sex and seroconverted. A cotllnon finding was a latent period, lasting for 4 to 18 months, when only viral antigen (sandwich EIA) or anti-gag antibodies alone (Western blot and CIA-RA) were seen.C|inically. no symptoms except for an abrupt seborrheic dermatitis in some were recorded. During this time. T cell numbers were normal but a defect was seen in cell med ated inlnunity to soluble recall antigens in half of the cases, and in no one neutralizing antibodies could be detected with the sensitive ATH-e cell microassay. Using RNA in situ hybridization. rare positive cells of monocyte—dendritic cell lineage were seen. In the maJorlty of the cases a full blown anti-viral antibody response developed first after a verified DNA virus (EBV, HBV. CMV) infection whereafter TH cells started to diminish. It is possible that these viruses enhance HIV replication by transactivation. Neutralizing antibodies appeared first after the full seroconversion, and the highest neutralizing titers were reached along with the development of lymphadenopathy. A fourfold rise in the neutralizing antibody titer during the follow-up period favoured a nonprogresslve clinical course. M2120 Human-Imunodeficency Virus Induced Hyperimunoglobulinemia and Its Associations with C05 (Leu 1) Expression on B Cells. D. J. MOODY, HARRY HOLLANDER, Y.J. HANG, D.P. STITES, UCSF School of Medicine, San Francisco, CA 94 43. We hypothesized that elevated inmunoglobulins in HIV-infected subjects were related to the increased proportions of CD5+ (Leu l+) B cells, human equivalents to the Lytl+ B cells in mouse disease models. Analysis of circu- lating levels of IgG, and 19A in healthy controls and HIV infected individuals indicated that there was a significant (p<0.0l) correlation (r=0.67 and 0.42, respectively) with the proportions of 605+ B cells in peripheral blood. Individuals infected with HIV had significantly (p<0.00l) greater proportions of B cells expressing C05 and total serum immunoglobulins than did healthy controls. These changes were directly related to the severity of the disease state of the HIV seropositive individuals (healthy homosexuals 100,000 Daltons) as well as lower molecular weight viral proteins, ELISA (ENI) and 1nd1rect fluorescent antibody (IFA) techniques. Five of 12 sera showed p24 and gp 110/120 Dupont immunoblot reactivity and IFA reactivity. All but one of the 5 sera were also ELISA reactlve. Subsequent sera were obtained from 2 of the 5 patients, Including the patient with the ELISA negative serum, at 14 and 34 days after the Initial speclmens. These later specimens both demonstrated p24, gp 41, p55 and gp 110/120 reactivIty on Dupont immunoblot as well as IFA and ELISA reactivity. Sera from the remaining 7 patients studied demonstrated p24 but not gp 110/120 Dupont Immunoblot react1v1ty and were non-reactive by IFA. Only 1 of the 7 sera was reactive by ELISA which was determined to be non- spec1f1c. Subsequent sera obtained from 2 of the 7 patients after 25 and 28 days again demonstrated only p24 reactivity on Dupont immunoblot and were non- reactive by IFA and ELISA. Sera from all 12 patlents were absorbed with H9 cell lysate and were tested by Immunoblot for reactivity to HTLV-I and HTLV-II viral antigens. Absorbed sera retained HIV p24 reactivity. None of the sera demonstrated p24 reactivity with HTLV-I or HTLV-II antigen. Studies of “p24 Only" Immunoblot Reactlvity to Human Immunodeficiency M2130 HTLV—I Associated B Cell Transformation: A Model for the Study of AIDS-Related 3 Cell Lymphoma. CONSTANCE A. RAINER. VL NG. JW MARSH. J LIFSON. MS MCGRA’I‘H, UCSF and San Francisco General Hospital, San Francisco, CA. USA. The recent observation that sera from a high proportion of AIDS-related B cell lymphoma patients react with both HTLV—I and HIV proteins (Feigal, et al, this meeting) has led us to investigate one of five immortalized human B cell lines derived by cocultivation of a lethally irradiated I-ITLV—I infected and immortalized T cell line (CS—l) with normal human tonsillar cells. We found that this 5 cell line, HKA—S expresses and secretes IgM, and produces HTLV—I envelope glycoprotein, ngl. Two dimensional gel electrophoresis further showed that secreted HKA-a 1911 had anti-GPGI activity. A mouse monoclonal anti— idiotypic antibody developed against HKA—S lgM bound to cell surface forms of HKA-a IgM and competed with HTLV-l for cell binding. In vitro proliferation studies revealed that both purified HTLV—I and anti-idiotypic antibodies specifically increased HKA—s cell proliferation, while control monoclonals and purified HIV had no effect. These studies describe an immortalized B cell line, HKA-S, transformed in association with HTLV—I, which produces its own antigen, gp61. Similar to normal B—lymphocytes, HKA-a cells proliferate, at least in part in response to this antigen. Because HTLV—I may play a role in B cell transformation in vivo, this system may provide an interesting new in vitro model for the further investigation of AIDS-related B cell lymphomas. MONDAY, JUNE 1 M2131 Isolation of HTLV-III/LAV Using Monocyte/Macrophages as Targets for the virus SUZANNE GARTNER, R.C. GALLO AND M. Biology, NCI/NIH, Bethesda, MD. HTLv-III/LAV isolates have been recovered from brain and lung tissues of patients with AIDS. These tissues contained virus-positive cells which exhibited characteristics of mononuclear phagocytes. These isolates had a significantly higher ability to infect monocyte-macrophages (MM) than T cells.(Gartner, et.al” Science, 333:215, 1986 and JAMA, 256:2365, 1986 It is conceivable that this preferential tropism can account for the considerable variability in the isolation of the virus from specimens of HTLV—III/LAV—infected individuals utilizing conventional T cell culture techniques. Using peripheral blood-derived MM and T cells as targets for the virus, we attempted virus isolation from a number of specimens Several isolates were recovered from brain, peripheral blood adherent cells, lung and skin using MM cells as targets. In most cases, we failed to isolate virus from these specimens using T cells for cocultivatiom Isolates from peripheral blood T cells could be readily recovered by both MM and T cell targets. In contrast, isolates from thymic tissue were recovered by T cell but not by MM cell cocultivation. These results further suggest that different variants of HTLV-III/LAV exhibit a perferential tropism for MM or T cells. Furthermore, because the longevity and magnitude of virus production in MM cells exceeds that of T cells, MM cells are more efficient targets for virus rescue. POPOVIC, Laboratory of Tumor Cell M2132 Correction of Lymphocyte Dysfunctions .11 vitro in ARC and AIDS Patients as a Consequence of Isoprinoaine+lnduced Changes in Th Cell Subsets and Antigen Presenting Monocytes (LeuM , Ia ). PETER H. TSANG, Y. SEI, J. GEORGE BEKESI, Mount Sinai School of Medicine, New York, New York 10029 Peripheral blood leukocytes from ARC and AIDS patients were analyzed follow- ing PHA and PWM induced lymphocyte transformation with mAb(s) that identify developemental flHLA-DR) and functional T-cells and monogytes.+ Significant decreases in both suppressor rigulating T subset (Leu3 Leu8 ) and the reci- procal inducer T subset (Leu3 LeU8 ) responsible for inducing differentiation of B cells were observed. Simultaneously, the percentage of effector T and the precursor Ts cells were increased, both of which were required for geneia- tion of suppression of cell mediated immunity. There was a selection of la cans bearing Leu2 (T9 markers and a concurrent reduction of antigen presenting monocytes and activated T cells. Data suggest that the functional deficien- cies in AIDS may be causeE by defects in T cell activation as well as antigen presentation by monocytes. Isoprinosine stimulated B cell functions of ARC and AIDS patients, in a se- lective fashion restoring both T cell dependent PWM induced transformation and the spontaneous secretion of immunoglcbulins by plasma cells while having no effec s on posting B-cells. Isopr nosing induced an increase in regulator T (Leu3 Leu8 ) and inducer T (Leu3 Leu8 ) cells while potentiating Ia antigen on T and monocytes during Blastogenesis. These events initiated a cascade of cellular interactions leading to restoration of cell-mediated immune responses. These interferences with the defective helper/suppressor regulatory pathways may have important therapeutic implications. MP133 Monocyte Function in a Male AIDS Patient and His Identical Twin ' Brother. Phillip D. SMITH, L.M. WAHL, I. KATONA and S.M. WAHL. Cellular Immunology Section, LMI, NIDR, NIH, Bethesda, Md. To explore whether monocyte dysfunction may contribute to the impaired lymphocyte proliferative responses in AIDS, we compared the accessory cell function of monocytes from an AIDS patient with that of his healthy, heterosexual, identical twin brother. Monocytes and T lymphocytes from the twins were purified by counterflow centrifugal elutriation. The phytohemag- glutinin (PHA)-induced proliferative response of the patient's lymphocytes in the presence of his own monocytes was 13,000 cpm whereas that of his brother's mononuclear cells was 102,500 cpm. However, replacement of the patient's monocytes with those of his healthy brother resulted in a 3-fold increase in FHA-stimulated lymphocyte DNA synthesis. In addition, the patient's monocytes produced (301 the interleukin 1 (IL-1) activity of his twin brother's monocytes. Therefore, we added purified exogenous IL-l to cultures of the AIDS patient'a T cells plus his defective monocytes which resulted in a 3-fold augmentation of DNA synthesis. Since the surface glycoprotein HLA—DR, a class II histocompatibility antigen, is required for accessory function, we also analyzed by fluorescence activated cell sorter the expression of HLA—DR on the monocytes from the twin subjects. Although the percentage of HLA-DR monocytes was reduced in the AIDS patient (55%) compared with that of his brother (83%), the density of HLA-DR on the patient's monocytes was 2.5 times greater than that expressed on the brother's monocytes. Thus, monocyte accessory cell function in an AIDS patient was reduced compared with that of his identical twin brother, and this reduction was due in part to reduced IL-l secretion and not to reduced expression of HLA-DR. Accessory cell dysfunction may contribute to the immunosuppression in AIDS. 32 MP134 Anti—class II antibodies in A113 patients and AIIS risk groups. SILVIA de la BARRERA’,‘ LEONARDO FAINBOIM”; GUILLERMO MUGiINIK*,GAS- TON PlCCHIO? SILVIA LUGO“? MARIA M.E.BRACCO. *IIHEMA, Academia Nacional de Nb» dicina, ** CIMAE, Buenos Aires, Argentina. The specificity of anti-lymphocyte antibodies against class I and class II antigens was evaluated in AIDS patients and iniindividuals at risk of AIDS (R— AIDS: male homosexuals (Ho) and hemophiliacs (He)) with positive or negative serology for HIV. Anti-class II antibodies capable of inducing antibody-dependentrcell—media— ted cytotoxicity (ADCC) against non-T cells and B lymphoblastoid cell lines (P3HR-1K, Raji) were detected in AIIS patients and in R-AIDS with or without HIV infection. This finding was confirmed by experiments in which class II antigens in target cells were blocked with monoclonal anti—class II antibody (DA6.231) and the cytotoxic reaction induced by patient's sera was abolished. In contrast,ADCC was not impaired by preincubating the target cells with monoclonal anti«class 1 antibody (W6/32). Prevalence of antibodies to non-T cells was confirmed by standard C-mediated microlymphocytotoxicity. In addition to ADCC and C-mediated cytotoxicity,anti-c1ass II and anti-class 1 antibodies were assayed by their ability to interfere the binding of fluor- escein labelled anti—class II (HLA-DR,Becton Dickinson) and anti-class I (W6/ 32) antibodies to peripheral blood mononuclear leukocytes (PBMC), non200 kd, ~65 kd and 9-17 kd. A substantial degree of purification was obtained after affinity chromatography on hydoxyapatite, and active fractions eluted from this medium were used to immunize rabbits and mice, which produced antisera (IgG-fractions) capable of immunoprecipitating the antiproliferative activity. Abbott Laboratories, Un- MR136 Malignant Prurigo of AIDS BERNARD LIAUTAUD*, J.W. PAPE**, J.A. DEHOVITZ**, R.I. VERDIER*. M-M, DESCHAMPS*. H.D. JOHNSON, JR.**, et al., *GHESKIO, Port-au-Prince, Haiti, **Cornell University Medical College, New York, N.Y. During the period July 1983, to December 1984, we observed that 66/134 (492) Haitian AIDS patients had intensely pruritic skin lesions (prurigo) for which neither specific etiologic nor categorical diagnoses could be established. Comparable lesions were not noted in 127 siblings and friends, but were present in 6 HIV seropositive spouses of the AIDS patients. Prurigo was an initial manifestation in 792 of these 66 patients and appeared a mean of 8 months prior to the diagnosis of AIDS. PrUrigo was characterized by multiple erythematous round macules or papules which first appeared on the extensor surface of the arms but subsequently involved the legs, trunk and face- Histologically the lesions were characterized by varying degrees of mixed (predominantly eosinophilic) perivascular inflammatory cell infiltrates of the dermis. The lesions did not respond to any therapeutic regimens employed and usually persisted throughout the AIDS illness. Demographic and laboratory data did not distinguish AIDS patients with prurigo from those without prurigo. MONDAY, JUNE 1 M2137 CLINICAL AND IMMUNOLOGICAL FEATURES OF HETEROSEXUALS INFECTED WITH HUMAN IMMUNODEFICIENCY VIRUS (HIV). 3E BRETTLE, AJ France, ME Jones, CM Steel, GW Neil, PL Yap, City Hospital, Blood Transfusion, Edinburgh. An epidemic of HIV began in Edinburgh amongst heterosexual intravenous drug misusers (IDM), one third of whom are female, in August 1983 and reached 50% seropositivity by 1985. Edinburgh has a large cohort of HIV infected heterosexuals Only 40% of individuals infected via drug misuse are currently misusing. We examined 115 HIV seropositive individuals, 5 homosexuals, 1 blood transfusion recipient, 3 heterosexual contacts of IBM and 106 IDM. Eighty two per cent of them have lymphadenopathy at two or more non—inguinal sites, 76/101 have elevated IgG levels, 4 have had clinically significant thrombocytopaenia, 15 have a leucopaenia <4.0x10(9)/1 and 39 have a lymphopaenia <1.4x10(9)/1. We performed lymphocyte subset estimation on 78 individuals and 22% have T4 cells <0.25x10(9)/1, 54% <0.5x10(9)/1 and 83% <0.9x10(9)/1. There was no excess of current misusers or females in any of the catergories. Significantly a total white cell count missed 71% of patients with a lymphopaenia and a total lymphocyte count missed 41% of those with a T4 count <0.9x10(9)/1. Within 4 years of infection there are significant clinical and immunological abnormalities in a heterosexual population who acquired infection via IDM despite the fact that only 40% are currently participating in a high risk activity i.e. IDM. These abnormalities are present despite the discontinuation of the high risk activity for up to 3 years in some individuals. As yet we are unable to say if progression is associated with continued IDM. GROWTH FAILURE IN CHILDREN WITH HEMOPHILIA AND HIV INFECTION. Francine Kaufman* and Edward Gomperts, Univ. of So. Cal. Medical School, Childrens Hosp. of L.A., L.A., CA, USA It is not known whether infection with HIV virus in children with hemophilia affects growth. As a consequence, the growth of 22 males with lymphadenopathy syndrome secondary to HIV virus and hemophilia was evaluated. 66% were below the 50th percentile for age but only 3 patients (pts) were found to have sig- nificant growth failure of 3-4 yrs duration with the onset after HIV infection. The pts were well except for lymphadenopathy; none had opportunistic infec- tions. Height for weight was between the 25th and 50th percentiles. Results of the endocrine evaluation which included the peak growth hormone (GH) response to arginine-insulin and glucagon tolerance tests are listed. M2138 Pt Age Bone Height Tanner Growth Rate SmC Peak GH # Yrs Age Age stage Cm/Yr U/Ml Ng/Ml 1 15.3 14 14 2 4.7 1.2 21.7 2 14.7 11.5 11 1 3.2 0.53 20.2 3 8.5 6 5 l 3.0 0.4 14.1 (Normal (n1) growth rate>5 cm/yr; nl SmC 6-11 yrs, 0.50-2.06, 12-17 yrs, 0.78— 3.73; n1 peak GH >10 ng/ml). All had normal thyroid function and cortisol res- ponse to insulin induced hypoglycemia. Pts 1 and 2 had mean 24 hour GH concen- tration (GHC) determined by measuring GH every 30 minutes (normal> 3.0 ng/ml). The GHC level was n1 in pt 1 (4.95 ng/ml) and low in pt 2 (2.17 ng/ml). CONCLUSION: Growth failure in pts with hemophilia and HIV infection is not rare and does not appear to be due to classical growth hormone deficiency. In some pts, this may be the consequence of the neurodysregulation of growth hormone secretion and may,be associated with hyposomatomedinemia. Further evaluation of these pts needs to be performed to determine the incidence and etiology of growth failure. MR139 THE SPECTRUM 0F PERIPHERAL NEUROMUSCULAR MANIFESTATIONS WITH HUMAN IMMUNODEFICIENCY VIRUS (HIV) INFECTION. JOSEPH R. BERGER, JOHN A. DIFINI, MARC A. SWERDLOFF, D. RAM AYYAR, University of Miami School of Medicine, Department of Neurology, Miami, Florida. Peripheral neuromuscular manifestations occurred in association with HIV infection in 29 patients (12 AIDS or ARC; l7 asymptomatic HIV seropositives). Seven patients presented with a subacute polyradiculoneuropathy resembling Guillain-Barre syndrome (GBS) with decreased nerve conduction velocities and increased CSF protein (5). All seven had full functional recovery within one to six months. More than 5096 of the patients with GBS seen at our institution were HIV seropositives. Twelve patients presented with a slowly progressive peripheral neuropathy manifested by increasing weakness (3), dysesthesia (4), or both motor and sensory syptoms (5). Electrophysiological studies revealed the neuropathy to be demyelinative in eight and axonal in four. CSF protein was typically increased (47- 138 mg/di). Two patients developed brachial plexitis with weakness of the serratus anterior, deltoid and the spinati and one had mononeuritis multiplex. Recurrent Bell's palsy (3) and zoster sine eruption (3) were also noted. Two patients developed a generalized myositis characterized by elevated muscle enzymes and abnormal electromyography. Peripheral neuromuscular manifestations may occur early in the course of HIV infection, long before the development of AIDS. These disorders are diverse in nature and often disabling. 33 M2140 Neuropsychologic Evaluation of HIV Seropositive US Army Soldiers D. HABURCHAK, S. HARRISON, L. ANDRON, R. GRAPE, R. HANNON, w. CLAYTON. Fitzsimons Army Medical Center, Aurora, CO USA Thirty—three HIV seropositive asymptomatic soldiers identified on unit screening were staged by Walter Reed classification and assessed for neuro— logic disease. The 32 males and 1 female had a mean age of 28.1 and staged 7 as WRl, 23 WRZ, and 3 WR3. Five patients, all WRZ, had subtle neurologic findings to include slowed rapid alternating movements, upper extremity hyperreflexia, facial palsy and diminished short term memory and digit span. Ten patients had CSF IgG index by nephelometry > .75, suggesting intrathecal IgG synthesis. lgG index was not significantly different between abnormals and normal exam patients (.98t.52 vs .62:.20 p=.49). One patient each with nogmal exam had abnormal EEG and MRI. Nine patients had 6-13 lymphocytes/ mm in CSF, 2 had CSF protein 50-70 mg/dl, none had CSF/serum albumin ratio greater than .0065, and all had positive CSF HIV Western Blot when diluted 1:10. Mean WATS-R PIQ scores were non-significantly higher in WRl than WRZ (108.4118.S vs 97.7:12.7 p=.56) and in normal exam versus abnormal exam patients (101.7:14.6 vs 92.4t11.9 p=.43). Two patients had positive CSF ETA and were treated for neurosyphilis. At six month follow—up all patients remain on active duty with five of five showing mean WATS—R PIQ improvement of ill.6iS.8 and none showing progressive neurologic disease. ““2141 The Importance of Clinical and Laboratory Parameters in the Management of AIDS Pneumonias B. G. GAZZARD, M. ANDERSON, T. GARDNER, St. Stephen's Hospital, Fulham Road, Chelsea, London, SW10 9TH. A diagnostic bronchoscopy which was performed in N3 of 52 consecutive patients with opportunistic pneumonias in the Acquired Immune Deficiency Syndrome (AIDS) did not reveal a cause in 6. Thus there were 15 patients without a definitive diagnosis but all responded to high dose Cortimoxazole and 9 developed other signs of AIDS within six months. In 25 of the 52 patients Pneumooystis pneumonia (PCP) was confirmed as the opportunist, but in only 3 was this by sputum induction. Cytomegalovinm (CMV) was grown from bronchial lavage specimens in 15 patients but only confirmed by transbronchial biopsy in 2. The lower the admission partial pressure of oxygen (PAO2 ) the higher the diagnostic yield at bronchoscopy. Seventy-five percent of our patients tolerated a full course of Cotrimoxazole. The mortality in patients with mixed infections (20%) was identical to that for PCP alone. Two of 5 patients in whom only CMV infection was found, and 6 of 10 patients with both PCP and CMV responded to Cotrimoxazole therapy alone. The most potent indicator of prognosis was the admission PAO (mean 9.6 KPA for survivors, and 6.7 KPA for non-survivors. P<0.0l). Simple observations of temperature and pulse were sensitive indicators of survival. Repeated chest X-rays, blood gases and bronchoscopy did not influence the management. lamcpsydfiatric Vimsmfectim: madaumitialsazemingmlmfimoffimnsemnl/Bisanmmn. __*__*, D. ,o.szmis*,c.mclomm*, B. W, J. m“, et . JdmI-kpldmudversity, Baltimore, MD; “lhiva'sityof MI *Nortlnastmtl‘dversitmcdmp,manitteulltimmrm studyof nerdfestatims detailed WW2),MIH,EEE,GFMI ,vhere arprtpriate. 363 mmszaad:155vateI-IIV 've (SN),]571aibemsettpcsitive(SP)>30mfis,arfl4el'ai (50min; muerted nmthsofdzeetvatim. 'Ihefregacyofpositivityofnmelscreafirg preseted: HiaseIIReEetralby 30 is WWII-148) BaltimreabmlNBZE) 17 so mm 3 4 0 WWW 12 (14s) 3 (Gt) 2 (12%) 6 (8%) 11 (10%) 8 (26%) ' anmtmy 7(a)1(2%)1(o%)14(19t)20(1s9‘)7(23%) omit-Jive Failurs cast. 6 ( 7%) 1 (2%) 2 (12%) 13 (18%)15(14%) 7 (23%) Nazqasydnmgimlmests 21(25t) 7(15\)4(24%) um) 9(a) 2(a) opt-amavirxatimimc - - - 5(7%) 7(6%) 2(a) 'ndsptaimixmymalyaishflimtsareladvelymguateofpcsitivesmemkg,m autl'iteegrwgs,irnlmixgsexuegativs. Mist-correlatim‘ willchfimfiiepzwalaneof disordeem-dfl'iemvevalueof tl’aRnselscreea. smumiumwumofuammmimmceue Mormonism. MONDAY, JUNE 1 M2143 Neurological Recovery and Prolonged Survival in Progressive Hul tifocal Ieukoencemaloptly with HIV infection m B. DEREK”: LENNART MUCIKE**._ *Dept. of Neurology, University of Miami School of Medicine, Miami, FL; 1“Dept. of Neurology, Harvard Medical Sdiool, Boston, MA. Pathological 1y confirmed progressive multifocal leulcoencerhalopathy' (PMIJ was the initial manifestation of HIV infection in two individuals, a 39 year old Inwsexual man and 36 year old bisexual women. Both patients experienced a drastic, though incomplete, recovery of neurological function and have survived in excess of 17 and 22 months, respectively, since the onset of their neurological symptoms. Neurological improvarent correlated with improvement of abnormal immunological parameters in one patient, whereas, the other patient displayed neurological recovery despite deterioration in her immunological status and development of other opportunistic infections. An uncharacteristically intense inflammatory response for PHI. was observed in the brain biopy specimens in regions where the papovavirus was detected by electron microscopy. In 13 other HIV seropositive patients with pathologically confirmed PML, progressive neurological deterioration and death within 6 months were observed. However, these two cases illustrate that PML associated with HIV infection may demonstrate neurological recovery and prolonged survival. MP1“ Polymyositis Associated ‘with AIDS Retrovirus ' MARINOS C. DALAKAS‘, G.H. PEZESHKPOUR“, M. GRAVELL‘, ILL. SEVER", *NINCDS, NIH, Bethesda, MD., MArmed Forces Irstitute of Pathology, Washington, D.C. 4 Two homosexual men were initially seen with polymyositis as the only manifestation of the acquired immunodeficiency syndrome (AIDS) retrovirus infection. They presented with progressive proximal muscle wealmess, elevated CPK and signs of inflammatory myopthy in the muscle biopsy. They developed AIDS-related complex a few weels later and typical AIDS two to six months after onset of muscle weakness. A third patient presented with dermatomyositis having the typical skin rash on the face, around the eyes and on the chest, in addition to the other clinical and laboratory signs of inflammatory myopathy. By \se of anti-human T-cell lymphotropic virus type III antiserum and monoclonal antibodies to lymphocyte subsets in an immunofluorescence technique, viral antigens were found in the OKTll-positive lymphoid cells suromding muscle fibers and invading the endomysia septa. We conclude that an initial infection with the AIDS retrovirus can be associated with polymyositis or dermatomyositis and this may be the first clinical manifestation of an impending AIDS-related complex or AIDS. M2145 Progressive Neuropsychological Deficit in HIV Infection IGOR GRANT*, J.H. ATKINSGN*, C.J. KENNEDY, D.D. RICI'IMAN*, S.A. SPECTOR, J.A. MCCUTCHAN, UCSD School of Medicine, La Jolla, CA, USA, *San Diego Veterans Administration Medican Center, San Diego, CA, USA, *UCSD School of Medicine, La Jolla, CA, USA. To determine the characteristics and prevalence of cognitive deficit in HIV infection, we performed neuropsychological (NP) assessments of I. groups of homosexual men. 1) AIDS (N=15); 2) ARC (N=13); 3) other HIV positive (Nelé); 4) seronegative (N=ll). All subjects were ambulatory and none presented with clinical signs of AIDS dementia complex at time of testing. Results. Neuropsychological abnormality was detected in 87% of AIDS, 54% cf ARC, AA); of other HIV seropositive, and 9% of seronegative men. Slowed infor— mation processing was the most common finding, followed by impaired ab- stracting ability and defects in learning and remembering. Conclusion. It is possible that.cognitive impairment occurs early in HIV infection and may be detected even in those who do not qualify for diagnosis of AIDS or ARC. 34 MP145 Regression of Oral Hairy Leukoplakia with Acyclovir LIONEL RESNICK*,J.HERBST*,D.V.ABLASHI**,S.Z.SALAHUDDIN**,B,FRANK*, S.ATHERTON***,et a .,*Mount Sinai Medical Center,Miami Beach,FL,**National In— stitutes of Health.Bethesda,MD.***Universlty of Miami School of Medlcine,Miami, FL. The epithelial cells of the HIV-associated lesion,oral "hairy" leukoplakia (0HL),contain actively replicating Epstein-Barr virus (EBV). Orally administer- ed acyclovlr therapy resulted in clinical regression of OHL in 5 of 6 patients. Regression of OHL was associated with an inability to detect EBV in the area of previously recognized OHL. A pilot study was conducted to evaluate acyclovir therapy (1.2gm/day for 20 days) in 13 HIV seropositive homosexual males with OHL involving the lateral borders of the tongue. The presence of EBV in the lesion of OHL was documented by electronmicroscopy (herpes-type particles),immunofluorescence assay (IFA) using 2 different monoclonal antibodies against EBV-VCA,ifl situ hybridization, and by the presence of elevated levels of EBNA-infected Cal 5 after transforma- tion of human fetal cord blood lymphocytes upon cocultivation with OHL tissue. Adjacent uninvolved tongue had no evidence of EBV antigens by IFA or in situ hybridization. All patients had the presence of elevated levels of EBVTVCA and EA antibodies in the serum. Clinical regression of OHL occurred 14 to 28 days after initiation of therapy. After discontinuing treatment.0HL recurred in all 5 cases (range: 10-46 days). No regression of OHL was evident in the 7 un- treated individuals after 6 months of follow-up. Regression of OHL was associ- ated with an inability to detect EBV by IFA and 13 situ hybridization in the previously involved area of OHL. It appears that EBV infection and replication is directly responsible for the clinical lesion of OHL. Acyclovir therapy in- hibits the replication of EBV resulting in regression of the OHL lesion. MP147 "False—Positive" Antibodies to Human Immunodeficiency Virus (HIV) Detected by an Enzyme-Linked Immunosorbent Assay (ELISA) in Patients at Low Risk for Acquired Immune Deficiency Syndrome (AIDS) FRANKLIN R. COOKERILL, III, M.D., R.S. Bdson, M.D., R.C. Chase, B.S., J.A. Katzmann, Ph.D., H.F. Taswell, M.D., Mayo Clinic and Mayo Foundation, Rochester, MN. © ELISA testing for anti HIV antibodies using the Abbott kit was performed on 290 sera from patient from 2 groups: (1.) at high risk for or having symptoms of HIV infection and (2.) at low risk for HIV infection (231). Group 2 included patients with non HIV related immune deficiencies, dermatologic, neurologic, collagen vascular or hematologic disorders. 25 patients had high absorbancy ELISA results (>1.0 abscrbance units). All of these patients had positive western blot (immunoblot) analyses and were all in Group 1. 20 patients had moderate or: 10.1 ELISA results (41.0 absorbence units). 2 of these 20 patients had positive western biots and were in Group 1. The remaining 18 patients were in Group 2. 8 of these had chronic liver disease, 4 had multiple myeloma and 6 had various disorders. These 18 patients presumably had "false positive" reactions for HIV using this ELISA test. M2148 Lymphoid Interstial Pneumonitis (LIP) in HIV-I or HIV-II infected pa- ti nts L.J. COUDERC , S. MATHERONZ, F. BRUN—VEZINETZ, P. HERVE3, C. MICHONZ, lP. CEAUVEEI. 1 : Hopital Saint—Louis 75010 Paris. 2 : Hopital Claude Bernard 75019 Paris. 3 : Hopital A. Béc'lére Clamart —FRANCE- Eleven adult patients [9 male, 2 female ; haitian (7 cases), african (3 cases), caucasian (1 case) werelinvestigated for interstial pneumonitis. In 10/10 ca— ses, lymphocyte count was increased (>140 x 10 /ml) in bronchoialveolar lavage fluid and in 4/5 cases more than 80 76 of the lymphocytes were Tg. No pathogens were isolated. In 5 patients, open lung biopsy showed the histo ogical picture of LIP. Ten patients had persistent generalized lymphadenopathy (PGL), and the caucasian patient had AIDS. Blood T4-cell count were decreased (S 600/ml) in all patients. HIV I-IgG antibodies were detected in 9/11 patients. The homoser- xuélcaucasian man lived in Mauritania ; he showed IgG antibodies to HIV-II. During a mean fdllow-up time of 30 months (9-36), 3 patients had recurrent bacterial infections ; their frequency decreased by use of I.V. gammaglobulin in 2/2 cases. Four PGL patients developed opportunistic infections. The HIV-II infected caucasian patient died of a high-grade lymphoma with lung involvement. Lung is a pulmonary manifestation of HIV—1 or HIV—II infection. LIP seems to be more frequent in black patients. MONDAY, JUNE 1 ““2149 Isolation of HIV from cerebrospinal fluid of patients with AIDS related disorders. DANIEL VITIEQQQ*,M.HARZICK*,F.FERCHAL*.Y.PEROL*,B.AUTRAN*,JC.CHER MANN . St Louis Hospitai,**Institut Pasteur,Paris,France . we evaluated biological involvement of CSF by HIV in a prospecti ve study by viral culture (reverse transcriptase activity) in the CSF of 10 preAIDS patients (Walter Reed classification),13 AIDS without neurological symptoms,10 preAIDS and lo AIDS with neurolo gical symptoms.HIV was isolated in the CSF in 15 patients without pleiocytosis «15 cells/mm3),and was correlated to viremia (13/15) Presence of HIV in the CSF is related to the general status (10/23 AIDS),or to the neurological involvement whatever the symptoms (9/20 AIDS and preAIDS).Only l preAIDS (WRS) without neurological symptoms was positive,all the other preAIDS patients were negative (5 WR2,3 WR3,1 WR4).Glycoprotein antibodies were found in the CSF in all patients by Western blot analysis (9p110.9p160).Intrathecal synthesis of antibodies was evaluated by ELISA and did not have a discriminating value.Presence of the Virus in the CSF should be investigated prior to any evaluation of an antiviral drug since a failure could be due to a silent neurological involvement (6/23 without neurological symptoms). A greater cohort of preAIDS patients is being evaluated and re peated lumbar puncture data will be provided 0 establish a correla tion with CT scans,general and neurological prognosis. M2150 Psychiatric Consultation to AIDS Patients, 1981-1986: A Consultation Liaison Perspective He w. Weismsn, E. Harvey, M.D. Nienaltow, D. Eaton, st. Luke's-Roosevelt Hospital Center, New llork, N.Y., U.S.A. The psychiatric morbidity associated with Human Immunosuppressive Virus(HIV) infection reflects varied biopsychosocial etiologies and may require adapta- tions in the provision of consultation services. The psychiatric care of AIDS patients was evaluated by reviewing all service consultations to AIDS and ARC patients between 1981 and 1986 at St. Luke's Hospital, a 776-bed teaching faci- lity in New York. Specifically, these were evaluated in terms of reasons for consult requests, time between admission and consultation, number of psychia- trist's visits, psychiatric diagnosis, and treatment. The data were compared to similar data for all general hospital patients consulted by psychiatry in the same years. In the 5 year study period, the number of consultations to HIV patients in- creased l7-fold. The most common psychiatric diagnoses were adjustment disor- ders (2h%) and organic brain syndromes (ZhE). Neuroleptic medication was used frequently (28%). There were also variations in the treatment of patients in different risk groups. Compared with general hospital patients, reasons for requesting consultations were similar (principally depression, suicidal ideation, and treatment refusal) although HIV patients required 1/3 more visits than did general medical pa- tients. Differences were also observed in the distribution of psychiatric diag- noses and in the provision of suicide precautions. The evaluation of psychiatric consultation data provides clinicians with a way to gauge the effect of AIDS on psychiatric services. Furthermore, it offers measures of the psychosocial morbidity and clinical needs associated with AIDS. Iflfl151 Absence of Correlation Between Serological Results, Neutralizing An- tibody Titers, and Progression of HIV-related Disease HARRY HOLLANDERt J HIGGINS**, N PEDERSEN**, J YEE**, J CARLSON** *UCSF School of Med1cine, San Francisco, CA, USA **UC Davis School of Medicine, Davis, CA, USA He reviewed serologic and neutralization antibody data on 50 random HIV sero- positive patients to determine whether any serological markers of clinical out- come exlsted. At the time of initial specimen acquisition, 20 subjects were asymptomatic or had HIV-related diseases but not AIDS. Eight had KS and 22 had prior opportunistic infections with or without KS. The major serologic change over time was the loss of the p24 antibody band. Eight of 11 subjects with this pattern had had opportunistic infections. Patients with and without the p24 band initially had similar rates of development of KS or new opportunistic infections, and when loss of the band was seen, it usually occurred after the onset of opportunistic infections. Serial ELISA titers were done on 51 sub- jects. Eight of 31 had at least a four-fold fall in titer over the period of observation. Only 2 of 8 had the fall in titer before the development of op- portunistic infections. Five had a decline in titer after disease progression and 1 was clinically stable despite the decline. Similar results were seen wlth titer of inmunofluorescent assays. Neutralization activity was measurable in 30 of 31 subjects at titers of 1:4 to 1:128. Titers were stable over tine and there was no correlation between neutralization titer and initial diagnosis or eventual progression of disease. Utilizing current serological techniques and serial specimens, we find that changes in HIV antibody titer and inmuno- blot pattern are insufficiently sensitive and specific to predict course of disease. Similarly, neutralizing antibody titer is not a good prognosticator of disease progression. 35 Salivary Gland Function in Early AIDS Patients C.-K. VEH, K.A. BUSCH, D.K. HEIDLEIN, P.C. FOX and B.J. BAUM CIFCFT_NYDR, NIH, Bethesda, MD, USA Saliva plays a primary role in modulating oral microbial colonization patterns. Reports of xerostomla and oral candldiasis in AIDS patients suggest the possibility of altered salivary gland status. The purpose of the present study was to assess salivary gland performance in early diagnosed AIDS patients. All patients were homosexual or bisexual males. HIV culture positive t cutaneous Kaposi's sarcoma and/or lymphadenopathy. Patients were divided into two groups; those being treated with AZT and others who had received no treatment. Two control groups were used: healthy men and male patients with complaints unrelated to salivary glands. Parotid and submandibular/subllnguil sallvas were collected on ice and stored at ~70' until analysis (volume, Na , K , Cl', total protein, albumin, lysozyme). There were no marked differences found between AIDS 1 AZT patients and the non-AIDS control groups wlth respect to electrolytes, total protein and salivary flow rates, for parotld and submandibular/sublingual glands under both basal and stimulated conditions. However, the frequency with which albumin was observed in saliva of both AIDS groups was dramatically increased; being seen in 48/73 AIDS saliva samples but in none of the 64 control samples. Albumin in gland saliva indicates the loss of salivary epithelial integrity. Also both AIDS groups had 2-3 fold higher levels (than controls) of lysozyme, an antimicrobial protein secreted by salivary ductal cells. The data demonstrate (I) early-diagnosed, metabolically stable AIDS patients show evidence of specific salivary gland dysfunction and (2) AZT therapy has no effects on salivary performance. These results suggest that study of salivary antlmlcrobial factors will be important with respect to the development of oral opportunistic infections. M2152 M2153 CARLO GIAQUINTO*,A.DE ROSSI*',A.VAGLIA"‘,G.CADEO*"',A.AMADORI'*,F.ZACCHELLO', et al.,'Dpt. of Pediatrics,*’Institute of Oncology, University of Padova,"'Dpt. of Infectious Diseases, Vicenza,‘“**Dpt. of Infectious Diseases, Brescia, Italy. To investigate the natural history of perinatal HIV-1 infection we studied ba- bies born to mothers belonging to high risk groups.Fifty eight infants and chil- dren born to HIV—1 seropositive mothers have been studied over the last two yams. Blood samples were obtained at birth or in the first six weeks of life in 45 ca- ses.All babies were evaluated serologically,virologically,and clinically every two monthe:neuromotor assessment and evaluation of mental development were also performed.Sera collected at birth or in the first six weeks of life from 45 udfise were positive for IgG specific antibodieszhowever 30% of babies older than six months became seronegative.Cultures from peripheral blood lymphocytes.tested for reverse transcriptase activity.were negative in all seronegetive childrensadhnce derived from 9 out of 25 seropoaitive children,older than six months,were positi- ve in the reverse transcriptase assay. Two infants had AIDS and 7 AIDS-related complexes.To date the other babies younger than 18 months are clinically well and laboratory data are in normal ran ge.In most of the older asymptomatic children T4/T8 ratios are< 1.0.A1though so: me babies received live oral polio vaccine and/or are shedding Cytomegelovirus in the urine, none of them present clinical signs of infection due to these viru— ses.Neurological development is normal in all asymptomatic infants while mental evaluation is in progress. Natural history of HIV-1 infection in children. MR154 Human immunodeficiency virus (HIV) —related polyradiculoneuropathy (PRN) : lack of evidence for antiperipheral nerve antibodies (PNA). SERGE PRZEDBORSKI', C. LIESNARD *, Ph. VOORDECKER ’, H. TAELMAN **, J.M. GERARD *, S. SPRECHER *", et al., ‘ Hopital Erasme, Brussels, ** Institut de Médecine Tropicals, Antwerpen, *" Institut Pasteur du Brabant, Brussels, Belgium. Five patients (pts) who presented with flaccid paraparesis and high cere- brospinal fluid (CSF) fig! antibody level were investigated in evolutive phase. Four of these pts met the criteria of AIDS. Clinical picture consisted of progressive distal and symmetrical weakness, with abolished reflexes. Mild sensory impairment was present in 3 pts and absent in 2 pts. Nerve conduction velocities were slowed in 3 pts. CSF protein was elevated (mean 364 mg/dl) and white cells were 2 to 109/mm3. Sural nerve biopsy performed in 3 pts showed segmental demyelination with intact axons and no inflammatory cells infiltration in 2 pts and was normal in 1 pt. Intrathecal synthesis of El! antibodies was found in 3 pts and CSF culture was positive for H1! in 1 pt. All pts displayed polyclonel hypergammaglobulinemia. Except for El! infec- tion, other causes of PRN were excluded. The presence of circulating PNA was investigated by incubating normal nerve with pts‘serum and CSF then with FITC-conjugated antibody to IgG, IgM and IgA. No binding was observed. The presence of immunoglobulin deposits in aural nerve biopsy was investigated in 3 pts by immunostaining with FITC-conjugated antibody to IgG and IgM. No deposits were observed. These data suggest that the pathogenesis of Ely—related PRN is not mediated by PNA. MONDAY, JUNE 1 MP155 Analysis of Bacteremias in Patients with AIDS. ' LEWIS SQHEAQEB, RS KLEIN, K FREEMAN, M MOTYL, L RICCI, GH FRIEDLAND. Montefiore Med. Ctr./N. Central Bx. Hosp./A. Einstein Coll. of Med., Bx,NY,USA Bacterial infections may cause significant disease in patients (pts.) with AIDS. To explore this issue, we studied bacteremias (Bs) occurring in a well- defined AIDS population. Microbiology records at Montefiore Med. Ctr. (MMC) and N.Central Bx Hospital (NCB) were reviewed for all significant Bs occurring between 1/82 and 7/86. Es were cross-referenced with a registry of pts. with AIDS hospitalized during this time. Available records for these pts. were re— viewed. Sixty-nine Bs occurred in 58 of 306 (19%) AIDS pts. for a rate of 22.5 35/100 AIDS pts. At MMC during this period 2,244 35 occurred in 83,955 pts. without AIDS for a rate of 2.7 35/100 pts. (p<0.05). The occurrence of B among pts. with AIDS was not significantly associated with risk group, age, gender or race. However, 3 due to S. aureus was significantly more common in pts. with intravenous drug use as Eheir EeIrarchical risk behavior for AIDS (p<0.05). Organisms most frequently causing B included g. aureus (21 episodes) S. pneu- moniae (12), salmonella sp. (12), P. aeru inosa (7) and other gram negative Bacilli (13). Six episodes were polymicro ia . Twenty—six of 54 (482) evaluable Bs were community acquired, 22/54 (412) were nosocomial (701 of S. neumoniae were community acquired, 692 of §: aureus nosocomial), and the rEmainder could not be classified. Eighty percent 0 B occurred at or following the diagnosis of AIDS (782 of community acquired, 96% of nosocomial). In 452 of patients with B, the infection causing B was the reason for admission. Survival analyses re— vealed no significant shortening of life expectancy among AIDS pts. with B. We conclude that AIDS pts. are at significantly increased risk for B regard- less of risk group or other demographic variables. Therefore, the increased rate of Bs in AIDS pts. is likely the result of HIV infection. Although 35 are frequent among AIDS pts. they do not appear to significantly influence survival when appropriately diagnosed and treated. ME156 Pregnancy Outcomes and HIV Infection in Intravenous Drug Abusers A SELWYN, ANAT R FEINGOLD, EE SCHOENBAUM, K DAVENNY, V ROBERTSON, J SHU'LMAN, et al., Montefiore Med. Ctr., A. Einstein Col. Med., Bronx, NY, USA. Beginning 7/1/85 we studied the effect of HIV infection on outcome of known pregnancies in intravenous drug abusers attending a NYC methadone program. Both seropositive (SP) and seronegative (SN) women enrolled in a prospective study of HIV infection were monitored for early pregnancy with monthly urine testing. Additional women were tested for HIV serum antibody (Ab) after conception. 0b— stetrical and infectious complications were monitored and serial HIV Ab and T-cell studies performed. Among women not pregnant at the time of initial HIV Ab test— ing, 12/71(17Z)SPs vs.19/145(13Z)SNs became pregnant over 18 months of follow-up. Among pregnant women informed of HIV Ab status 524 weeks gestation, 4/10(AOZ) SP vs. 6/17(3SZ)SN elected to terminate. 33 pregnancy outcomes occurred in 26 SPs without AIDS or oral thrush (mean age 30), and 45 outcomes in 44 $115 (mean age 29). N b f S t El t' L bi h L bi h . ngcgmeg A ggtggggus Ectopics Tei‘rcnirlixgions" gyeweg sS >§Ieweg sS SPs 33 BE”; 0 1493.3 392 13E39 g *p=NS SN5 45 2 5% 2(52) 11 242 7 16 ) 23 50% 0f 44 women carrying >24 weeks (155?,29SN), mean third trimester hemoglobin levels (11.4 vs. 11.5) were not different. SP women had lower lymphocyte counts (1769 vs. 2319) and T-cell ratios (0.88 vs. 1.65, p(.05). 5/15(33Z) SP5 were hospitalized for infections; gastroenteritis(2), pneumonia(2), cellulitis(1),vs. 2/29(7Z) SNs; gastroenteritis(1), pyelonephritis(1), (p(.07). The frequency of other medical and obstetrical complications during pregancy or at delivery did not differ between the two groups. There were no differences in self-report of drug abuse during pregancy. HIV Ab was not associated with a decreased occurrence of pregnancy in SPs, nor with early or late adverse pregnancy outcomes. Data suggest that pregnant SP women may be at increased risk of serious infectious complications. Frequency of elec- tive termination was not significantly increased in SP women. These findings have important implications regarding perinatal transmission of HIV infection. ACQUIRED IMMUNODEFICIENCY SYNDROME (AIDS) ASSOCIATED RENAL DISEASE: A LONGI'I‘UDINAL ANALYSIS. mm EA. Friedman. SUNY Health Science Center at Brooklyn, N.Y., USA. Over a four year period between 1982 and 1986, among 800 patients with AIDS seen at two urban institutions, 95 were evaluated for renal abnormalities consisting of varying de- grees of azotemia, proteinuria and hematuria. We classified renal disorders in AIDS on the basis of clinical presentation, hospital course, and renal histology (when available). There were 23 patients with potentially reversible acute renal failure (ARE); 54 patients with AIDS associated nephropathy (AAN); and 18 patients who developed AIDS while underwing maintenance hemodialysis (AIDS-MB) (Table). ARE M2157 YEAR AAN AIDS-MH Cr<6 Cr>6 Cr<6 Cr>6 '82 0 0 0 2(2) 1(1) '83 2 1(1) 2 9(7) 0 '84 1 8(4) 4 9(7) 4(4) '85 1 1(0) 0 9(3) 6(6) '86 2 7(1) 4 1502) 7(7) TOTAL 6 17(6) 10 4401) ”(18) Number ( ) represents pts dialyzed Among the ARF group, 6 of 17 with serum Cr>6 mg/dl who were dialyzed, 5 recovered sufficient renal function and survived without further dialysis for a median 17 months. In the AAN group, 44 of 54 patients developed irreversible uremia, and 31 were repeatedly dialyzed. Median survival of dialyzed AAN patients was 1.4 months. In the AIDS-MH group, all 18 patients were IV drug addicts, who developed AIDS within 7 months (median) of in- itiating maintenance hemodialysis. Their median survival after diagnosis of AIDS was 1 month despite dialysis. From these data we conclude that renal failure both acute and chronic in AIDS is increasing and survival continues to be very poor. 36 ME158 Hypoxemia and neutrophilic alveolitis as prognostic Factors of Pneu— mocystis carinii pneumonia (PNC.C.P.) in HIV infected patients. Pierre FOURET, F.PARQUIN, J.P.BEDUS, J.F.SICARD, C.M.MAYAUD, J.ROLAND et a1. Pathology and Chest Departments, Tenon Hospital, PARIS, 75020 - FRANCE. This study concerns 46 HIV infected patients (pts) with PNC.C.P. and without identifiable associated infection. At the time of diagnosis of PNC.C.P., Pa02 and BAL data [total cells, number and percentage of lymphocytes (L) and neutro- phils (PMN)] were evaluated. All pts were treated with Irimethoprime—Sulfametho- xazole (TMP-SMZ) ; they were divided into 2 groups, according to the evolution of their pulmonary disease (0 I : 10 with fatal acute respiratory failure ; G 11 : 36 with a favorable outcome). The significant correlations between initial P802 and/or BAL data (cell count/run} - G I 107177 ;G 11 1891120) and evolution are indicated in the following table. 0 Nb pts P802 PMN PMN/L P802 <50 PMN>5/mm3 PMN/L) 0.5 N mm Hg 9.; n pts/N n pts/N n pts/N I 10 52 1 13 26 1 25 0.57 1 0.9 7/10 9/10 7/10 11 3s 67 1 19 10 1 13 2.9 1 4.2 8/36 18/35 10/36 p<0.02 p<0.os p<0.001 p<0.o1 p<0.03 p<0.01 It is to be noticed that : 1)There is a significant relation between P802 and PMN (‘36) and Z)Post—mortem examination of lung from8 G I pts showed fibrosis in 7 cases. Conclusion : Initial Pa02<50 mm Hg and PMN/L (in BAL)>0.5were present in 5/10 pts of G 1. Even though this association was also present in 4/36 pts of G II, it seems a poor prognostic factor and, when present, probably indicates that other initial treatment, e.g. a IMP-SMZ/steroid association, should be considered. M2159 Progressive Multifocal Leukoencephalopathy (PML) in AIDS Patients: Diagnostic Considerations and Pathologic Findings. S.A. HOUFF, D. KATZ, C. KUFTA, G. ELDER, D. VACANTE, E. MAJOR, NINCDS, NIH, Bethesda, MD. PML, a subacute demyellnating disease due to JC virus (JCV), is seen frequently in AIDS patients. We have previously reported the use of i_g fl hybridization with a biotinylated JCV probe in the diagnosis of PML. Three AIDS patients with PML have been studied with this technique on either brain biopsy or autopsy tissues. In one patient, the diagnosis of PML was established within 1‘ hours of biopsy by l_n fig hybridization performed on frozen sections using a modified technique developed by one of us (EM)). Formalln-fixed biopsy tissue confirmed these findings. Areas of demyelination associated with JCV infection of oligodendrocytes, and astrocytosls were found throughout the biopsy. In another patient, areas of demyelination found in biopsy tissue had none of the other pathological features of PML Igfl hybridization ' with the JCV probe demonstrated infection of oligodendrocytes, which confirmed the diagnosis of PML. Autopsy studies in two patients revealed extensive demyellnation in the white matter of the cerebral hemispheres. In one, JCV infected cells without other pathologic changes were found scattered throughout the cerebral hemisphere and PML lesions extended into the cerebral cortex. Our studies suggest that PML in AIDS patients is often more extensive and histological changes may be more subtle than when the disease occurs with other lmmunosuppressive illnesses. The use of In situ hybridization is essential in rapidly establishing the diagnosis of PML in patients with AIDS. M2160 The Need for Tissue Diagnosis of Central Nervoul System Lesions wltg the Acqulged lmmunodelicikgncy Syndromgh ELIAHU BISHBURG , J. SLIM , E.S. JOHNSON aR' KAPILA , R.H.K. ENG NJ. State Department of Health, Trenton, St. Michael's Med. Ctr., “*Univ. Hosp., Newark, *VA Med. Ctr., East Orange, N.J. none 9 Patients with acquired Immunodeficiency Syndrome (AIDS) who have central nervous system (CNS) lesions and positive toxoplaama serology are often presumed to have cerebral toxoplasmoele and are treated accordingly. We examined records for 600 AIDS patients retrospectively and round A7 with CNS lesions on CT scan. Lesion types included multiple and single ring enhancing as well as multiple and single hypodensitiel. Nineteen of these patients had positive toxoplasma serology. Of the thirteen with brain biopsies, 6 had toxoplnsmosis, 2 had tuberculosis, 2 had encephalitis of unknown cause, 1 had nocardia and salmonella, 1 had vacculitie and 2 showed nonconclusive results. Biopsies of 3 of the patients with significant toxoplasma serology showed no evidence of toxoplasmoeie. The majority of the cases (36) had been presumptively diagnosed as having toxoplesmosis and treated with antl—toxoplasmosis regimen--pyrimethamlne and sulfadiazlne (30) or pyrlmethamine and trlmethoprim-sulfamethoxazole (6). That 8 of the 13 biopsies revealed diseases other than toxoploamosie, some of them treatable, suggests that other diseases may be common and that biopsies of CNS lesions in AIDS patients are needed to make accurate diagnoses to detect treatable diseases and to avoid unnecessary treatment. MONDAY, JUNE 1 MP161 Sclerosing cholangitis in AIDS PIERRE—MARIE GIRARD, C. MARCHE, C. LEPORT, C. MICHON, D. ZOUBI, A.G. SAIMOT et al., Hopital Claude Bernard, 75019 Paris, France. Cholangitis was documented in 6 out of 101 AIDS patients (pts) whose liver histology was available (surgical biopsyzl, needle biopsyz53, autopsyz68). Right hypocondrial pain and prolonged fever were present in 4 patients. Anicteric cholestasis occurred in all patients and was major in 4 (alkaline phosphatases : 8 x normal value). Diagnosis was made by endoscopic retrograde cholangiography and laparotomy (1 pt), needle biopsy (2 pts) and/or autopsy (4 pts). Sclerosing cholangitis associated with pericholangitis predominated on proximal intrahepatic biliary ducts. In 5 cases, numerous typical cytomegalovirus (CMV) inclusions were present in both biliary epithelium and endothe- lial cells. In one case, no intra-hepatic biliary duct inclusions could be found at autopsy although CMV cholecystitis was present. All patients had CMV viremia and disseminated CMV infection () 2 organs). These data show that cholangitis occurs in 6% of AIDS patients and is one of the multiple factors involved in the frequent cholestasis. Needle biopsy could underestimate its prevalence because of the predominant proximal biliary duct involvement. Cholangitis is mainly due to CMV but can also occur without any opportunistic agent as already reported in other immunocompromised status. MR162 Children's Hospital AIDS Program (CHAP): I Demographic and Clinical Data 1984-1986 EDWARD CONNOR, S. MORRISON, M. BOLAND, L. EPSTEIN, V. JOSHI, J. OLESKE Chi dren 5 Hospital of New Jersey & UMD-New Jersey Medical School, Newark, NJ Sixty three children with symptomatic HIV infection were enrolled in CHAP from 1984-1986. 46% AIDS; 54% ARC. Male:fema1e ratio 0.85:1. Ethnic origin distribution: Black 52%; Hispanic 24%; White 21%; Haitian 3%. Risk factors: mother IVDU 40%; mother sexual contact of IVDU 30%; both parents IVDU 10%; neonatal transfusion 6%; maternal transfusion 5%; hemophilia 3%; Haitian 3%; multiple risk 1.5%; unknown 1.5%. Excluding hemophiliacs, mean age at enroll- ment was 1.88 yrs (0.2-7.75); 11/61 were enrolled at >4 yrs. 16/63 (25%) of patients were first seen to be screened for HIV because of known risk: 8/16 were healthy; 8/16 had chronic symptoms; 35/63 were first seen for acute ill- ness. Among these 63 children, signs and symptoms over 2 yrs included: rash 95%; lymphadenopathy 92%; hepatosplenomegaly 87%; fever 84%; respiratory findings 79%; thrush 71%; encephalopathy 68%; FTT 56%; recurrent otitis media 49%; abdominal distention 48%; diarrhea 43%; clubbing 21%; gingivostomatis 19%; parotitis 11%; abdominal pain 11%; CHF 8%; epistaxis, joint pain, conjunctivitis, GI bleeding, jaundice <5%. There were 23 opportunistic infections (8 PCP, 8 Candida, 2 Toxoplasmosis, 3 disseminated CMV, l disseminated adenovirus, 1 MAI); 4/63 had neoplastic disease (1 CNS lymphoma, 1 GI leiomyosarcoma, 2 pulmonary lymphoproliferative disease). 29 episodes of bacterial sepsis occurred; 20 streptococcal; 4 Salmonella spp.; 3 H. influenzae; 2 S. aureus. (57%) of children. HIV is a chronic multisystem disease with protean mani- festations. The practitioner must maintain a high index of suspicion for HIV infection in children. MR163 DETECTION OF INFECTIOUS HUMAN IMMUNODEFICIENCY VIRUS (HIV) IN SEROPOSITIVE INFANTS AND CHILDREN PEGGY S. WEINTRUB, M.A. KOERPER, C. WALKER, D.W. NARA, J.A. LEVY, M.J. COWAN Departments of Pediatrics and Medicine, University of California, San Francisco, CA 94143 While the majority of children infected with HIV develop antibody, a significant number may have undetectable infectious HIV in their peripheral mononuclear cells (PMC). We evaluated 26 seropositive children for the presence of infectious HIV in their PMC and assessed in vitro immunologic parameters and clinical status. of the 13 seropositivs, culture negative children, 6 acquired their infection from infected mothers, 2 from blood transfusions, and 5 from factor VIII/Ix transfusions. Normal T and B cell immunity were found in 8 out of 13 and 11/13 were clinically well. In contrast, of the 13 children who were seropositive, culture positive (5 maternal transmission, 4 blood transfusion, 4 factor transfusion), all (13/13) had abnormal T cell and B cell immunity. of the 13, 12 had AIDS or ARC and 2 have died. In 10 of the seropositive, culture negative children followed prospectively there has been no significant disease progression. In 4 seropositive, culture positive children detectable virus was associated with clinical and/or laboratory deterioration. Our results suggest that in seropositive children the presence of detectable HIV in PMC correlates with severity of laboratory and clinical evidence of disease and may be an important prognostic factor. LIP/DIP was documented in 23/63 37 M2164 DIFFUSE CERVICAL CELLULITIS ASSOCIATED WITH HIV 1 INFECTION IN CENTRAL AFRICA. E. VUILLECARD*, c.c. MATHIOT**, M.C. GEORGES-COURBOT**. A.J. GEORGEsii, Centre National Hospitalier Universitaire, Bangui, Central African Republic (CAR). **Institut Pasteur, B.P.923, Bangui, CAR. within a seven month period ten cases of diffuse cervical cellulitis have been observed in the stomatological department of Bangui general hospital. All of them resulted from non-treated dental infection. Clinical symptoms showed emphysematous gangrene and large facial necrosis. Bacteriological examination of pus withdrawn by syringe under anaerobic conditions allowed us to identify in one case Fusobacterium nucleatum and in two cases Clostridium perfringsns, while no consistent interpretation was possible in seven cases. Nine of ten patients were HIV 1 antibodies carriers (ELAVIA and Western Blot) without any other symtom of confirmed AIDS. We consider acute diffuse cervical cellulitis as a possible first symptom of an A R C in HIV 1 positive patients, in Africa. In this syndrom (ARC), treatment consisting of large surgical debridement associated with penicillin and metronidazole therapy, has always been efficient. MP165 Asymptomatic Neurologic Infection in Persistent Generalized , Lymphadenopathy Syndrome Assgglated to HIV*Infection* a. ctorer ., J.M. BARRERA*.., g. ERCILLA ., n. GRIFOL ".{; TOR ., J. CANO ., E. ARGELAGUES . Infectious Diseases Unit, Blood Bank Unit, Hospital de Badalonn "Germans Tries i Pujol‘; Blood Bank Unit Hospital Clinic de Barcelona. Barcelona, Catalonia, Spain. We searched by ELISA and Western blot techniques antibodies to HIV in serum and CSF of 40 patients with EGL.All were intravenous drug addicts and none presented neurologic manifestations.All CSF analyzed were free from red blood cslls.In 10 patients (251) we found antibodies to HIV in serum and CSF by both methods.Resu1ts are listed in the following table: Patient No ELISA CSF VB CSF ELISA Serum VB Serum p18p24p33p41p55p68p110 p16p24p33p41p55p68p110 l + — - — - + + — + j: + - 4- + + - 2 + - + - + + + - + — + — + + + — 3 4- + + - + — - - e — v - + + + + 4 + + 4 - + + + — + - + - + + + - 5 4 — — - + - - — + - + — + — — - 6 + - + - + + + - 0 - + — + + + - 7 + - - — + — - - 4r - + - + + + - 8 6 + + — + - - - + + 4» - + + — + 9 + — - — + — - — + + + — + — + - 10 + + i - i - - — + + + — + - - + Leakage of HIV-specific antibodies from the serum to the CSF can not be excluded nevertheless immunoglobulins do not diffuse substantially into the CS? in the absence of brain or meningeal inflammation, what leads us to assume that these patients present asymptomatic CNS infection.Asymptomatic neurologic infection may be an early event in HIV infection.Follow-up may confirm our findings. ““2166 Development of antigen and antibody titers against various HIV-antigens in the course of HIV—infection RUDIGER HEHLMANN , A. FISCHER“, A. MATUSCHKE G.G. FROSNER , F.-D. GOEBEL*, V. ERFLE***. *Medizinische Poli- klinik, Mfinchen, *Max von Pettenkofer-Institut, Universitat Mfinchen, ***Abt. Molekulare Zellpathologie, GSF Neuherberg, Mfinchen Prognostic significance has been attributed to the presence and titer of HIV core and env antibodies. For this study, we analyzed sera from HIV-infected persons with different manifestations of the disease for the presence of HIV core antigen, and env anti— gen. We used the Abbott antigen EIA and HTLV-III antibody con— firmatory EIA to test for any and core and the Behring ELISA for whole virus. Healthy HIV—infected persons exhibit relatively high anti—core antibodies. With the development of LAS and AIDS the median antibody titers decrease as well as the overall percentage of positive persons. A trend to a transient increase of anti core titers has been observed in ARC patients. Most AIDS patients are negative for core antibodies. The lack of core antibody is usually associated with the presence of HIV antigen. In contrast, there are no remarkable changes of the usually high env—antibody titers during the process of disease development. These data in- dicate that the combined use of different HIV tests in HIV-in— fected persons during the course of disease development can be of prognostic value. MONDAY, JUNE 1 M2161 Dysmorphic Features in Children HIV Positive J.FERMOSEL, M.D. GURBINDO, T.HERNANDEZ SAMPELAVO, R.PEREZ GARCIA IPPP Hospital Provincial de Madrid. Spain. The majority of children infected by HIV are born to HIV positive mothers. Transmission of HIV may occur: early intrauterine; during materno—filial limpho- cytary transfusion; during or after delivery. Recently Marion et al. described an embryopathy probably caused by the first mechanism of transmission. We have studied the morphological features of 22 children HIV seropositive, aged between 3 months and 3 years; 11 males and 11 females. All of them were born to intravenous drug abusing and/or prostitute wo— men, HIV seropositive. The HIV antibodies were tested by both ELISA and IFI. The dysmorphic features found were: Growth failure 40% (Height and weight less than the third percentile for chronologic age); microcephaly 20% (HC less than 10th percentile); prominent forehead 45%; flattened nasal bridge 77%: long pal— pebral fissure 86%; blue sclerae 81%; obliquity of the eyes 36%; triangular phil trum 77%; marked and cleft prominence of the mental protuberance 59%; epicanthus 40%; low-set malformed ears 45%; markedly patulous lips 31%; simian creases 22%; horizontal and deep flexion creases in palms 31%; clinodactyly 9%. Not all children were equally affected with these dysmorphic features. The most characteristic alterations affected to eyes and eyelids (86%). These percn— tages are significative higher than those of children born to mother of risk— group but HIV seronegative. Neither intraocular nor cardiac stigmata were found. None mother was alcohol abuser. No other intrauterine infections were demonstra- ted but one by CMV. We confirmed, in our area, HIV associated embryopathy which also affected to the hands and feet. MR168 Clinical Patterns Emerging from longitudinal Study of Australian Haemophiliacs with HIV Antibodies. 3,;,GAgSlA,P.A.GATENBY,A.BASTEN,D.F.KENNY,K.J.GALLAGHER M.I.DELFIN Clinical Immunology Research Centre University of Sydney . NSW Australia HIV-ELISA confirmed by Radioimmunoprecipitation or Western Blot showed in 1934/85 a seropositive rate of his overall in a representative group of 161 Haemophiliacs from New South Wales. Retrospective analysis of the sera of this population using ELISA and Western Blot has now established that HIV antibodies were detectable as early as 1981. Serial monitoring of the clinical status and T cell subsets of these patients since 1984/5 apd a subgroup of them since 1983 has revealed that almost all the HIV Ab p tients have followed one of the patterns : A: Decline in CD4 ce ls associated with a fall in CD4:CDB ratio (14%) B: Persistent low CD4 or CD4:CD8 ratio (25‘) C: Rising level of CD4 or CD4:CD8 ratio from a low baseline (8%) D: Normal T cell subsets and ratio (39a) E: Wide fluctuations in T cell subsets in the absence of a precipitant(l4%) Three patients (33‘) with pattern "A" .one with pattern "B“ and one with pattern "E" have developed symptomatic immunodeficiency with three fatalities to date. Occasional episodes of autoimmune disease have occurred in patients with patterns “B“ and “C" but none of these individuals has developed symptomatic immunodeficiency. Whilst the very long term prognostic significance of these patterns occurring in the five years after infection has yet to be determined this data indicates that markedly abnormal T cell ratios may commonly persist in HIV exposed Haemophiliacs without an adverse short term outcome. ““3169 Spectrum of HIV Infection in Neonatal Recipients of Blood Products THOMAS M. MUNDY*,J. HARD**,J. ALLEN**,S. PEPKOUITZ*,D. GOLDFINGER*, L. LOEB***, et al.,*Cedars-Sinai Medical Center, ***L.A. County Dept. Health, Los Angeles, CA, **AIDS Program, Centers for Disease Control, Atlanta, GA. Neonates who received blood products from multiple donors prior to blood bank screening represent a popu ation at risk for HIV infection and may have a different presentation than infants at risk through vertical transmission. We have tracked 56 neonates who received 60 blood products gleaned from 7 donors who were later found to have AIDS/ARC/sero-positivity; 4 neonates each received products from 2 high risk donors. Two additional neonates received multiple transfusions resulting in AIDS but no high risk donors were identi- fied. 0f the 60 products generated, only 1 donation occurred following the institution of vo untary donor deferral in 1983. Fourteen patients had died prior to study, including 11 who died during their initial admission. HIV infection could ave played a role in 6 of these infants who lived 5 to 15 months after the implicated transfusion and who subsequently died of infectious causes. Forty-four infants were available for further study. 14/16 infants tested are infected with HIV. 5/14 died of AIDS 1-4 years after transfusion. 8/14 are living with AIDS/ARC at 4-6 years, including 4 in whom the diagnosis was not considered until antibody screening was performed. One patient is sero-posi— tive but well at 7 years. Only 2/16 screened were sero-negative despite an interval of up to 7 years between time of donation and confirmation of infec- tion in the donors. 0f the 28 patients remaining, 14 have been located and study visits are pending and 14 have not been located to date. Large numbers of neonates may have been infected with HIV prior to effec- tive screening programs. A spectrum of disease due to HIV infection in pedi— atric patients should be stressed as this diagnosis had not been considered in 5/14 of our infected children in spite of significant symptoms in 4 of them. 38 MR110 Arteriopathy in Children with AIDS V. JOSHI, BRUCE PANEL, E. CONNOR, J. OLESKE, S. MORRISON, J. MARIN- GARCIA, ET AL Children's Hospital of New Jersey, UMD New Jersey Medical School, Newark. NJ Pathologic features with special reference to arteries of different organs (heart, lungs, kidneys, spleen, intestine, brain etc) seen at autopsy in six children with Acquired Innune Deficiency Syndrome (AIDS) are described. Small and medium size arteries which were most connmnly involved showed: a) intimal fibrosis, fragmentation of elastic tissue, fibrosis and calcification of media variable luminal narrowing and b) vasculitis/perivasculitis. In one case, aneurysms of the right coronary artery with thrombosis and myocardial infrac- tion were seen. Vascul1tis/pervasculitis seen only in the brain may be related to the agent associated with AIDS encephalopathy. The fibrocalcific arterial lesions resemble Infantile Arterial Calcification of Infancy most closely but because of differences in age incidence, clinicopathologic and innmnologic features and size and distribution of involved arteries, the arterial lesions of pediatric AIDS appear to constitute a distinctive arteriopathy. Infection(s) secondary to innmnodeficiency resulting in increased exposure to endogenous and exogenous elastases may be related to pathogenesis. Role of HIV cannot be entirely ruled out. Luminal narrowing from the arterial lesions may be related to atrophy, cell depletion, scarring and necrosis/infarcts of different organs in children with AIDS. Pediatricians should be alert to the possibility of arterial involvement in pediatric AIDS. MP.171 GEORGE, ALAN M” and GRIFFITHS, Welsh AIBS‘Campaign‘”, Cardiff. This Campaign is an attempt on a country-wide basis to establish an organisation to tackle AIDS as a community, behavioural, social and edxxnioud problem rather than a medical one. The Campaign is funded by the Government but is independent of it. The aim is to provide up—to—date information for the public and pxiesiarfls to modify personal behaviour; to alleviate anxiety; to train volunteers, health educators and professionals; to provide advice to individuals and groups and to promote consistency in the message on AIDS presented by the media and others working in the AIDS field. It is thought to be the first project of its kind in a European country and will thus be of interest to people in other countries including the United States as considerable help was obtained from colleagues in New York and New Jersey in establishing the Unit. The demonstration will show in detail the programmes developed for use in schools, with voluntary workers, health professionals and intravenous drug abusers. The resources produced to meet the needs of these groups as a result of the above programmes will be shown. An evaluation programme is running concomitantly. WELSH AIDS CAMPAIGN C“*; Welsh Office*, Cardiff United Kingdom, and M2112 AIDS on Campus: Strategies for Response ROSE WALTON, Department of Allied Health Resources, State University of New York at Stony Brook, Stony Brook, NY The social and political impact of AIDS creates a complex epidemic with far reaching economic and psychosocial concerns for the health care and education systems. The School of Allied Health Professions. SUNY at Stony Brook has responded to the crisis through a community service project, and two major educational projects. The community service project provided an information and referral hotline as well as community educational and service activities. That project is now a free—standing agency in the community. The SUNY AIDS Education project is designed to reduce the fear and anxiety of AIDS in college students. A comprehensive curriculum was developed and field tested during the first year of the project and is being implemented on 50 of the 64 campuses of the university and community college system. The implementation phase in— cluded a training session for campus facilitators and an evaluation plan for the program. These projects were funded by the New York State Department of Health, AIDS Institute. The School of Allied Health Professions has been awarded a training grant from the National Institute of Mental Health to develop an AIDS resource centen This project will include faculty development, student education, in—service education, and provide consultative services and a quarterly newsletter. A discussion of these projects, their impact on the School and University in relationship to policy decisions will allow educators and health care administrators to explore strategies for influencing institutional responses to AIDS on the college campus and in health science centers in regard to stu— dents and employees. MONDAY, JUNE 1 M2173 The Application of Social Marketing Principles to AIDS Prevention and Education Programs: Implications and Considerations drawn from a Worldwide Survey GEORGE MARSHALL WORTHINGTON*, L. de la Macorra**, V. Prieto**, *Worthington and Associates Worldwide, New York City, NY, **Social Marketing International Asso~ ciation, Queretaro, Mexico. Social marketing is the design, implementation, and control of programs seek— ing to increase the acceptability of a social idea or cause in a target group. It utilizes concepts of market segmentation, consumer research. concept dee velopment, communication, facilitation, incentives, and exchange theory to max~ imize target group response. Synonymous terms might be "social cause market— ing," "idea marketing," or "public issue marketing." Social Marketing, as the application of basic marketing principles to gen— erate a social benefit, has proven its effectiveness in a number of family planning programs, particularly the retail sale of contraceptive products es— pecially in the developing countries. Social Marketing International Associa— tion, a professional membership association based in Mexico, decided to re—, search the feasibility of applying this experience together with basic market— ing principles to prevention programs designed to reduce the transmission of HIV. Six countries were chosen for case study presentation: the U.S.. U.K., Brazil, the Philippines, Zaire and France. Case study presentations of all country situations will be within the following seven point framework: 1) pro— blem definition, 2) goal setting, 3) target market segmentation, A) consumer analysis. 5) influence Channels analysis, 6) marketing strategy and tactics, and 7) implementation and evaluation. Special emphasis will be accorded the utilization of the research findings presented for the improvement or eatablishment of additional prevention educa- tion programs both in countries reviewed and elsewhere utilizing marketing. ME174 Relationships Between Knowledge About AIDS Risk and Actual Risk Be- havior in a Sample of Homosexual Men: Some Implications for Preven— tion. JEFFREY A. KELLY*, JANET 5. ST. LAWRENCE**, TEDDY L. BRASFIELD*, & HAROLD V. HO0D*, *University of Mississippi Medical Center, Jackson, MS, **University of Mississippi, Oxford, MS and University of Mississippi Medical Center. Ninety apparently-healthy homosexual men were administered an objective— format, 33—item test of knowledge about sexual practices high—risk for HIV transmission and a questionnaire eliciting information on sexual activities over the preceding twelve months. All subjects lived in a city where AIDS education brochures are distributed in gay bars. _ Correlations were computed between Risk Knowledge Test scores (x - 25.6 of 33. range = 9 - 33) and frequency of actual high—risk conduct to examine re- lationships between risk knowledge and risk behavior. Risk behavior in the sample ranged from very low (0 partners, no occurrence of anal intercourse) very high (200 partners, 96 occurrences of unprotected receptive anal inter- course). Pearson product-moment correlations revealed that AIDS Knowledge scores were BEE significantly related to number of different sexual partners (r = -.02), frequency of unprotected insertive (r = +.10) or receptive (r - —.15) anal intercourse, oral intercourse with semen entry (r = -.06), meeting partners at "sex clubs" (r = +.Il), or other risk behaviors. Regression analyses detected no relationships between AIDS risk knowledge and behavior. Research in other health/behavior areas indicates that information provision alone is often insufficient to change longstanding, immediately-reinforced risk behavior. In addition to informational campaigns, other community-based inter- ventions may be needed to promote risk behavior change. Examples of such approaches, and copies of study measures, will be presented. n D “IE175 Clinical and Immunological Features of 100 HIV Antibody Positive Individuals from an Alternate Test site JOHN HOWARD**,F.SATTLER*,R.MAHON*,J.SPERLING**,J.LEEDOM*,USC School of Medicine, Los Angeles, CA,**Edelman Health Center. Angeles, CA. We evaluated 100 HIV antibody positive persons from the only alternate test site in Los Angeles. Sixty—five were asymptomatic (Group 1) and 35 complained of systemic symptoms (Group 2), such as fever (31%), night sweats (61%), fatigue (66%) and weight loss (6%). Twenty-one ambulatory patients with AIDS manifested by a prior episode of Pneumocystis carinii pneumonia within 90 days (Group 3) served as controls. Irrespective of symptomatology, Groups 1 and 2 demonstrated clinical and laboratory evidence of immunodeficiency. Eighty had generalized lymphadenopathy, 16 onychomycosis, 6 oral thrush, and 2 biopsy-proven Kaposi's sarcoma. Despite normal white cell counts, 40 (62%) of Group 1 already had T4 lymphocyte cell counts below 500 cells/mm3 and 31 (48%) had below 300 cells/mm3 (mean 468 cells/mm3). Thirty-one (89%) of Group 2 had less than 500 T4 cells/mm3 and 16 (46%) had less than 300 cells/mm3 (mean 324 cells/mm3). Group 3 had the lowest T4 counts (mean 84 cells/mm3). Differences between mean T4 cell counts in the three groups were significant (P<0.001). In addition, 75% of Group 1, 80% of Group 2, and 100% of Group 3 were anergic to seven intradermal antigens. We believe the high frequency of clinical and laboratory evidence of immunodeficiency in subjects evaluated at the Los Angeles alternate test site justifies the allocation of funding for medical evaluation and follow—up care for other test centers with similar findings. Lee 39 ““2116 AIDS Educators Perceptions of Barriers to Effective Health Education: Report on a National Survey. NICHOLAS FREUDENBERG J. LEE. Hunter College/CUNY As part of a project conducted for the American Public Health Association to develop guidelines for effective AIDS education, investigators surveyed a convenience sample of 80 AIDS educators throughout the United States. Twenty-five respondents participat- ed in one to two hour semi-structured interviews, 25 were inter- viewed on the telephone and 30 responded to a mailed question- naire. Respondents were educators working on AIDS for public and private agencies A qualitative analysis of their responses revealed common organizational, educational and political barriers to effective education. Organizational problems included integrating volunteer and paid staff, balancing service delivery and prevention, coord- inating public and private efforts, and developing effective coalitions and networks. Educational problems included interpret- ing scientific information for the public, communicating effec- tively with diverse populations, inadequate time for planning and difficulties in evaluating the impact of interventions. Larger sociopolitical problems were difficulties in reaching minorities, inadequate resources and public resistance to open discussion about sex and drugs. Respondents described their assessment of the consequences of these obstacles and how they addressed these consequences. Invee- tigatore categorized these descriptions into specific behavioral responses to each obstacle. The report concludes with recommen- dations for more effective AIDS education. MB177 Interactive Simulation as a Tool in the Decision-making Process Prevent HIV Incidence among Homosexual Men in The Netherlands. MARCEL G.W. DIJKGRAAF*, G.J.P. VAN GRIENSVEN*, J.L.A. GEURTS**, *University of Utrecht, The Netherlands, *‘University of Nijmegen, The Netherlands. The current knowledge of the behavioral and physical system of forces which cause the spread of HIV among homosexual men is incomplete and scattered over a wide range of professional journals and reports. At the same time, the discussion on what the effect of certain preventive measures on behavior of the population at risk will be, is in an early stage. The use of a computer stored diffusion model on HIV among homosexual men can be a powerful, although hypothetical, discussion- and decision—aid when considering the dynamic effects of certain preventive measures. Formal models however, are mostly too complicated for an effective and widespread use in this respect. The procedure as proposed here, tries to solve this problem, by an integration of computer simulation with elements of gaming. The result is a so called interactive to simulation, in which persons—in-roles interact in a question-and-answer relationship with a formal dynamic model programmed for a computer. The instrument as designed consists of a) a formal computer stored model, in which the side perform existing knowledge on preventive measures and the behavioral and physical of HIV is defined clearly and b) a computer interaction procedure to simulation experiments with preventive measures and c) a discussion procedure for a group of persons with eachother and in interaction with the computer stored model, to explore and evaluate the short- and long term consequences of preventive measures on the spread of HIV among homosexual men. MP178 AIDS Prevention, Information and Education for Health; a model for a comprehensive strategy focused on the general public as well as special target groups; practised in the Netherlands since 1983. HANS MOERKERK*, Health Education Centre of the municipality of Amsterdam. In 1983 the national government, public health authorities and organisations affiliated with groups at risk for AIDS, joined hands and concluded that a com- munication strategy had to be developed with the object to inform and educate the population about possible HIV infection. Inside the model for the strategy, two general objectives were determined: (1) to help reduce the spread of infection, (2) to counteract prejudice and misconceptions as well as unjustified anxiety and fear. It was assumed that a 'step by step' approach had to be adopted: a short term strategy (supplying knowledge = one way communication) and a long term strategy (a process of systematized two way communication between sender and recipient of the message in order to cond1tion attitudes and values). In practice it meant that first attention was given to groups at risk which were approached by both health information and health education; through the years the prevention activities were extended to larger groups inside the general population and to the general public itself. Large scale evaluation activities were incorporated 1n this communication model, with promising results both on the level of knowledge and attitudes (cfv Tielman 1987)(cfv Eyrond 1987); also press coverage in general was informative and could be made part of this process of health promotion. The dutch approach received positive attention from other european countries and was a starting point for wider activities by The Council of Europe and the European Common Market. The model included active participation of advertising agents and marketing officers. MONDAY, JUNE 1 MR179 IDS Information and Prevention Concept in Switzerland BERTINO SOMAINI*, H. RYSER‘, F. GUTZWILLER", R. STAUB*", H. RIEDENER'**, *Swiss Federal Office of Public Health, Berne, Switzerland, "Institute of Social and Preventive Medicine of the University of Lausanne, Switzerland, "'AIDS Foundation Switzerland, Zurich, Switzerland 1. Initial position: All available epidemiological data show that, with res— pect to frequency of cases of AIDS and HIV infection, Switzerland leads the statistics for European countries. Thus, 26 cases of AIDS infection per 1 million inhabitants were recorded by September 1986. 2. Consequently, the federal health authorities have conducted various infor- mative campaigns in conjunction with the Swiss AIDS Foundation since end 1985. For example, in March 1985 a brochure was distributed to all house- holds. The results of this campaign were evaluated. 3. Since February 1987 the same instances have been running a national cam- paign stressing the features: a) use of the condom for all risk factor sexual contacts. b) no sharing of syringes for i.v. use of drugs. The results of this campaign will also be evaluated. The close cooperation between the official body (Federal Ministry of Health) and the private organization (Swiss AIDS Foundation) has been very fruitful to date. The work is explained briefly and the objectives and elements of the campaign and their evaluation presented. MB180 AIDS Prevention among Homosexuals in Switzerland ROGER STAUB’, H. RIEDENER‘, B. SOMAINI**, S. MOSER‘, *AIDS Founda- tion Switzerland, Zurich, Switzerland, **Swiss Federal Office of Public Health, Berne, Switzerland. 1. Initial situation: All available epidemiological data show that homosexual and bisexual men still constitute the major group effected. Thus, 109 of 170 (=64 %) cases are accounted for by this group. Epidemiologists estimate that some 15 t are infected today. 2. Objective: Prevention of new infection within this target group by educa- tion. All are aware that anal sex constitutes a high infection risk. All are aware that protection is pQSSible in sexual contacts outside a monogamous re- lationship of at least 6 years' duration by practising Safer Sex (= no unpro- tected anal practises, no sperm in the mouth). 3. Procedure: The AIDS prevention campaign comprises three features: - "The Hot Rubber”: The Swiss AIDS Foundation operates the "Hot Rubber Company" and markets the condom ("The Condom for the Gay Man") at all meeting points (bars, saunas etc.) and by direct mail. A poster campaign with "poster of the month" feature backs up the publicity. — The Safer Sex Campaign: with brochures, posters, advertisements and articles the Swiss AIDS Foundation draws attention to Safer Sex on the Swiss scene. - Discussion groups: Local AIDS Help group in conjunction with homosexual groups stage regional workshops on the subject of sexuality. The Swiss AIDS Foundation operates the national hot line to safer sex. 4. Evaluation: A first cross—section inquiry will be conducted in January 1981 Later, inquiries will be conducted every 6 months which should provide quali— tative results. The concept will be illustrated briefly, with examples, and the first evalua- tion presented. th181 An Evaluation of Using Ex-addict Outreach workers to Edu- ' cate Intravenous Drug Users about AIDS Prevention. WILLIAM E. MCAULIFFE*, S. DOERING**, P. EREER*, H. SILVERMAN***, B. BRANSON****, K. Williams****, *Harvard Medical School, Cam- bridge, MA, **Goucher College, ***Maryland Drug Abuse Administra- tion, ****HERO, Baltimore, MD We sent ex-addict outreach workers to randomly assigned areas of Baltimore to teach intravenous drug users (IVDU'S) about the dangers of AIDS. Interviews conducted before and one month after the intervention (85% of followups completed) with IVDU'S in exper- imental and control neighborhoods measured knowledge of AIDS and the frequency of high risk behavior; we also collected data on the number of experimental subjects who entered drug treatment, obtained an antibody test or sought additional information from an AIDS hot- line. The results showed that the outreach approach was feasible and effective in finding IVDU'S who were not in treatment and get- ting them to listen to a message and accept pamphlets on AIDS. The experimental subjects (n=236) had significantly more knowledge of AIDS at followup than did the controls (n=72), but behavioral changes (e.g., sharing and cleaning needles, use of condoms and obtaining an antibody test) were not significant. We concluded that this was an effective educational approach, but that greater behavior change would require more concrete interventions, e.g., distributing condoms and pocket-size bottles of bleach, making entry into treatment easier and bringing antibody testing to the street corners. 40 MP182 Prevalence of Antibody to Human Immunodeficiency Virus (HIV) and ' Client Characteristics in the Wisconsin Alternate Site Testing and Counseling Program, 1985-86 EDWARD A.BELONGIA, J. VERGERONT, fl BOWLING, J. P. DAVIS, Wisconsin Division of Health, Madison, WI USA In June, 1985 a program providing free and anonymous HIV antibody testing and counseling began at 30 sites other than blood or plasma centers in Wisconsin. As of December, 1986, 2856 clients had been counseled and completed a self administered questionnaire; 2789 HIV antibody tests were performed, of which 245 (9.5%) were repeatedly reactive by enzyme immuno- assay (EIA) and 197 (7.7%) positive by Western blot assay (WB). Among gay/ bisexual men using IV drugs, 26 (31.7%) of 82 were WB positive compared to 126 (9.9%) of 1272 gay/bisexual men who did not use IV drugs (p<.001) Analysis by race demonstrated 23 (40.3%) of 57 black gay males to be WE positive compared to 129 (10.0%) of 1289 nonblack gay males (p<.001); none of 31 black heterosexual IV drug users had detectable antibody to HIV. Prevalence of HIV antibody was less than 5% in all groups other than gay/ bisexual males. Among gay/bisexual men, 84% reported changes in their life— style or sexual practices due to concern about AIDS; 44.8% were not comfort- able discussing their lifestyle or sexual practices with their health care provider, but regional differences were noted. In Wisconsin, a state with a relatively low incidence of AIDS, there are subgroups of individuals with a high prevalence of HIV infection, the majority of whom reside in Milwaukee or Dane counties. Intrastate regional analysis of HIV seroprevalence and client characteristics is useful for the development of local educational programs directed toward individuals at increased risk of acquiring HIV infection. M2183 Prevention Policy on AIDS among Drug Addicts 1n Amsterdnm ERNST C. BUNING, Municipal Health Service Amsterdam, Holland By January lat 1987 Aids had been diagnosed among 7 i.v. drug addicts in the Netherlands. In Amsterdam 20-35% of the i.v. drug addicts has been infected by HIV. To prevent or slow down further spread of the virus is therefore of paramount importance. Apart from drugfrae treatment and resocinlisntion, the Amsterdam helping system consists of (1) contacting addicts in the drugscena, police stations and general hospitals, (2) harm reduction such as medical- and social primary care, methadone prescription (s.g. "methadone by bus project"), needle and syringe exchange and (3) health education. This approach is essentially non-moralistic. About 70% of the addict: is in touch with this helping system. Health education and needle and syringe exchange were intensified after Aida became a focal issue. Emphasis is placed on safe-sex and safe-druguse. Health education is carried out through leaflets, personal contact and condom distribution to addicted prostitutes. Slot machines were also installed to provide addicts with condoms. Needle and syringe exchange is possible at 13 different locations throughout the city. In 1986 350,000 needles and syringes were exchanged. No increase in needle stick accidents has been reported among the general population. Preliminary findings show that needle sharing has reduced. Counter effects of the harm-reduction program could not be found: the number of i.v. drug addicts has not increased, while the patient-load of drugfree treatment programmes has doubled over the last 6 years. MR184 Knowledge and Attitudes About AIDS Among College Freshmen in Louisiana WILLIAM L. ATKINSONI’Z, v. KTSANESI, s. HASSIGI'Z ITulane University School of Public Health and Tropical Medicine and 2Louisiana Department of Health and Human Resources, New Orleans, LA In spring 1986, we mailed an AIDS knowledge and attitude questionnaire to 3231 randomly selected freshmen attending seven universities in Louisiana; 967 responded. Their mean age was 18.5 years; 652 were female. Most (93%) were 1985 high school (HS) graduates, 722 from schools in Louisiana and the remain- der from schools in 38 other states. Only 28% responded that AIDS had been discussed in one or more HS Classes. The most frequently reported source of information was television (60%). More than 90% were able to correctly identify major high risk groups for AIDS (homosexual men, intravenous drug users), but 162 and 13% respectively added household members of AIDS patients and blood donors as being at high risk. Although more than 95% correctly identified major routesof transmission (sexual, sharing needles), 14% believed mosquitoes and 6% believed donating blood could transmit the disease. Respondent sex, type of HS, HS location,and discussion of AIDS in 3 HS class did not significantly affect knowledge score. Respondents reported that their knowledge of AIDS affected their behavior in the following ways: choice of friends-17Z, choice of sexual partners-59%, number of sexual partners-592, willingness to donate blood-182. Our findings indicate that college freshmen in Louisiana are well informed about major risk groups, transmission and prevention of AIDS but that consid- erable confusion exists concerning blood donation and casual transmission. MONDAY, JUNE 1 M3185 Knowledge and Attitudes about AIDS in Rhode Islanders BARBARA A. DEBUONO, J.BRONDUM, H.D.SCOTT, L.GREEN, N.FARAONE, Rhode Island Department of Health, Providence, Rhode Island. A random digit dial telephone survey was conducted in December, 1986. Four- hundred questionnaires were completed at a cost of $2,600. Fifty-six percent of respondents were women; median age and educational level were 39 years and 12 years respectively. Overall, general knowledge of AIDS transmission and risk groups was limited. While 86% said AIDS could not be spread by casual contact, 24% thought that sharing the same glass as a person with AIDS was a source of infection. Only 55% of respondents identified drug addicts as a risk group for AIDS and 20% identified hemophiliacs. Forty percent felt that AIDS would not be a problem in their comnunity, and only 38% considered the blood supply safe. Stratification of responses by age and educational level demonstrated that AIDS knowledge varied directly with educational level and inversely with age. For example, 75% of those with a college education identified drug addicts as a risk group while only 42% of those with less than a high school education did (X2 test for trend=26.9, p<.05);64% of those under 55 could identify drug addicts as being at risk for AIDS but only 34% of those 55 and over could do so (X2=27, p<.05). Those ages 18-24 were more likely than any other age group to have changed their sexual behavior since learning of AIDS (X2 test for trend=12.2 p<.05). Such telephone surveys represent a cost-effective method of identifying target groups for educational interventions and if applied periodically, can serve to measure their success. MP186 HIV Antibodies in Needles and Syringes Used By Intravenous Drug ' Users. ALEX D. WODAK‘, K.DOLAN*, A.IMRIE#, J.GOLD**, B.M.WHYTE*#, D.A.COOPER*#. 3Alcohol and Drug Service, #Centre for Immunology, St. Vincent's Hospital; *‘ Albion Street Centre, Sydney Hospital, *#NH&MRC Special Unit in AIDS Epidemiology and Clinical Research, Sydney, Australia. The sharing of needles and syringes by intravenous drug users (IVDU) has been recognised as a critical factor in the transmission of the human immuno- deficiency virus (HIV). A pilot sterile needle and syringe exchange programme was established in an inner city neighbourhood in Sydney, Australia in an attempt to reduce sharing of needles and syringes among IVDU. The contents of exchange syringes were analysed for antibody to HIV by ELISA; the contents of reactive and boarderline syringes were confirmed by Western blot. Of a sample of 300 needles and syringes exchanged, 1% were found to be antibody positive and thus potentially infectious. Analysis of positive and negative control syringes indicated that the proportion of potentially infectious needles found in this study may have underestimated the proportion of infectious injection equipment returned. These finding emphasise the importance of removing used needles and syringes from circulation in addition to supplying sterile equipment. This method of monitoring exchanged needles and syringes is suggested as a means of evaluating measures designed to reduce the transmission of HIV among IVDU. Rapid implementation of sterile needle/and syringe exchange programmes is imperative in Western countries to stem the spread of HIV infection. MR187 A Survey of Knowledge and Attitudes Amng Dentists Concerning AIDS 5. BRENT DOVE, JAMES A. 001m, University of Texas Dental School at San Antmio, San Antonio, '13. AIDS presents niany prdalars for various health care professicnals including daitists. 'n'iis is especially true with the renewed emphasis an infection om— trol in the dental professicn. In order to assess knolwedge of the average practicing dentist concerning AIES, approximately 1,200 dentists were surveyed concerning AIDS etiology, transnissim, epidemiology, oral nenifestatims, nethods of detection, treat- ment, prevention, and sociological and behavioral attitudes. It was hypothch sized that dentists in larger cities with a higher incidaice of reported AIDS cases would have a better understanding of AIIS and ARC than dentists in cities with fewer AIDS patients. , The results were analyzed using Pearsm ‘Product Mmem: Coefficient of Cor- relatim (Peaxsm's r). The results indicated that although there is a cone- 1aticn between the number of AIDS patients in a city and a better inderstanding of AIDS by dentists in that city, the increased knowledge did not generalize to all areas surveyed. other nethods of educating dentists cxncerning AIES, in- fectirn crntrol, and their role as health care professicnals concerning pa- tients with infectious diseases are needed. 41 Behavioral Diagnosis for Effective Education of HIV—Seropositive Patients. T* DAVID RABIN*, VIRGINIA TAGGART*, CYNTHIA BANDEMER*, and JOSEPH BELLONTI**, *Department of Community and Family Medicine, **Department of Pediatrics, Georgetown University School of Medicine, Washington, DC. MP.188 The US Surgeon General and National Academy of Sciences have recently advocated that control of AIDS will require widespread public education. Effective education, in turn, depends on a correct behavioral diagnosis. This paper describes how a behavioral diagnosis is accomplished as a basis for counseling HIV-positive patients. Such counseling should address various co—factors implicated in the progression of AIDS, and measures to stem the spread of the HIV virus. Previous research reveals the following barriers to making recommended behavior changes: low perceived efficacy of changing sexual behaviors, lack of AIDS knowledge, difficulty in controlling sexual impulses, high belief in biomedicine to cure AIDS, and non-supportive social norms. Additionally, anecdotal experience indicates that several barriers exist to HIV-positive patients seeking regular medical care: denial, social stigmatization, and fears about confidentiality of information. The paper concludes by describing how the behavioral diagnosis technique can be applied to training health professionals to better -care for and educate HIV-positive patients. ““2189 Prenatal diagnosis of congenital H.I.V. infection GILLES PIALOUX*, r. Daffos**, F. Forestier**, M.A. Rey*, F. Brun-Vezinet*, Laboratoire de Virologie, Hdpital Claude— Eernard*, Centre de diagnostic prenatal, Hépital ND Bon—Secours, Paris, France**. In order to find a way of distinguishing prenatally between infected fetuses and those who escape infection, we compared, in two cases, fetal blood samples with moflwr blood samples. Fetal blood was carried out at 24 and 27 weeks of gestation by direct puncture of the umbilical cord under ultrasound guidance, and only before a medical terminaison of the pregnancy. In these two cases, HIV antibodies were found in fetal blood samples. HIV was isolated from stimulated T lymphocytes and detected by reverse transcriptase activity only in one mother but not in fetuses. Immunological investigations did not demonstrate evident immnunodeficiency lymphocytes, T4/T8, ratio, platelets were normal. Non specific IgM titers were unelevated and lymphoid tissues did not present lymphocytes depletion. This preliminary study suggest that prenatal diagnosis of congenital HIV is available using this procedure ; even if many points must be discussed. The theoritical risk of contaminating an uninfected fetus through the fetal blood sampling itself is relevant. The absence of maternal blood contamination in fetal blood has been avoided. Further studies must etablish if no elevation of IgM and no isolation of HIV from fetal T lymphocytes are sufficient to eliminate HIV congenital infection. M2190 RICHARD MERRITT, M. ROWE, C. RYAN, Intergovernmental Health Policy Project, Washington, D.C. The presentation summarizes the findings of a PHS funded document detail— ing AIDS policy issues for state legislators and key health program officials. Basic policy questions are discussed in twelve major areas including: screening and testing, surveillance, confidentiality, potential discrimina- tion, needs of special populations, education, other modes of intervention, research, medical care. support services, financing and administration. A range of state legislative, program and policy solutions from all fifty states is described, highlighting specific case examples to illustrate how states have developed sometimes different and sometimes parallel solutions to similar AIDS related problems. Basic health policy concepts are also discussed to help states frame their own AIDS programs and policies. Testing, confidentiality and financing_issues are emphasized -- the latter focusing on AZT, its reimbursement, allocation, cost effectiveness and implications for developing insurance mechanisms and systems of care for persons with HIV infection. The study reconnmnds that AIDS may be used as a vehicle for developing paradigms for addressing fundamental health policy problems facing the states. These include designing systems for chronic care, financing catastrophic care and care for the uninsured. AIDS: A Public Health Challenge for States MONDAY, JUNE 1 ““9191 Disinfection of IV Drug Paraphernalia Using Commonly Available Materials: Hope for Controlling Spread of HIV Among IV Drug Users? SUNITA JAIN', N. FLYNN', E. KEDDIE', J. CAHLSON', S. HARPER“, V. BAILEY", et al.“ 'Univ of Calif. Davis, "Aquarian Effort, Sacramento, CA HIV is spreading rapidly among 0.5. IV drug users (IVDU) and will spread widely from them to new populations through heterosexual and vertical trans- mission (T). He have demonstrated that sharing of paraphernalia (P) continues despite reasonable knowledge among IVDU of mode of T. Few IVDU regularly practice disinfection of P between users We tested the ability of commonly available potential disinfecting agents (DA) to inactivate HIV using a sensitive infectivity assay and questioned IVDU regarding availability of these DA last time they shot up. HIV was not infective after exposure to dilute household bleach or dish detergent, rub— bing alcohol, vodka, or wine; beer and cola drink were ineffective. P with- stood exposure to each DA at least 50 times without showing significant da- mage. 70$ of IVDU related that one or more of these DA were easily available last time they shot up (bleach 351, rubbing alcohol 56’, wine 23$. liquid dish detergent H95). They expressed interest in learning simple techniques for disinfection of P using these commonly available DA. We are developing an instructional program for IVDU in drug treatment programs emphasizing a simple, practical, 2-step disinfection technique in which P are rinsed in any active DA and then in water before being passed to the next user. In the absence of decriminalization of P and changes in P-sharing habits, disinfection may offer the only hope for slowing the T of HIV among IVDU and, subsequently, to their sexual contacts and offspring. He have identified easily available DA and a simple disinfection technique which is effective i3 vitro. MP192 Follow-up Counseling and Risk Behavior Assessment of HIV Antibody ' Positive Military recruits BETH A. DILLON, N.SPENCER, Colorado Department of Health, Denver, CO, U.S.A. Military Entrance Processing Stations (MEPS) began screening new recruits in October 1985 by ELISA and Western Blot for HIV antibody (Ab). Positives are not provided interpretation of results or counseling by MEPS. Colorado Department of Health (CDH) regulations require reports of positives with identifiers. Seventeen have been reported to CDH by MEPS (seropositivity rate less than .ISX). All reported positives were male (11 white, 3 black and 3 hispanic). The average age for positives (25) is older than negative recruits where the majority are in the 17-19 age group. By January 1987, CDH completed follow—up on 16 positives and confirmed or provided counseling to 12 (75.0%), (2 were not located, 1 moved out-of- state). Only I declined counseling. Of the 12, 11 were retested, with one negative by both ELISA and Western Blot. Risk behaviors were evaluated for the 11 counseled and retested positives. Although prior to MEPS Ab testing, recruits sign an affidavit denying homosexual/bisexual activity, during the CDH evaluation 10 of 11 positives reported homosexual or bisexual activity as a risk factor. One claimed heterosexual contact with female prostitutes. Four of the individuals reported 2 risk behaviors. Transmission prevention counseling is essential for positives. health follow—up ensures counseling, permits identify pools of heterosexual HIV infection. Public risk assessment and may ”[3193 Minnesota Counseling and Testing Sites: Analysis of Trends Over . Time. RICHARD N. DANILA*, J.M. SHULTZ*, M.T. OSTERHOLM*, K.L. MACDONALD’, K. HENRY;*, M. SIMPSON;**. *Minnesota Department of Health, **St. Paul-Ramsey Medical Center, ***Hennepin County Medical Center, Minneapolis, MN, USA. Counseling and testing sites (CTS's) opened in MN in July 1985 to HIV antibody testing (w1th Western blot confirmation) to persons at hig for acquiring HIV Infection. Data obtained during the first 12 months of operation (4,906 client visits for 4,598 clients) were analyzed to assess trends over time. The overall seroprevalence rate for all visits was 10.8%. Among males, the highest seroprevalence rates were in homosexual men (422/ 2440 [I7.3%]). This rate did not change over time; however, the proportion of clients who were homosexual men significantly decreased over time when compared to the entire group (p<0.01). Thus, the overall monthly seropreva- lence rates declined significantly (p<0.01). The number of repeat visits increased significantly (p<0.01); however, this did not account for the ob— served decline in seroprevalence, because rates of seropositivity were similar for first-time and repeat visits (497/4,598 [10.8%] vs. 30/306 [9.8%]). During this time, a significant increase in the number of women clients being tested was noted (p<0.01). Because the seroprevalence rate for female clients was very low (5/638 [0.8%]), the increasing proportion of fe- male clients may have also contributed to the overall decline in the observed seroprevalence rate. Increases over time were noted in the number of hetero- sexual clients with sexual exposure to a high-risk partner, the number of clients reporting an HIV-antibody positive sex partner, and the number of clients with an unspecified risk or no risk. These changing client demo- graphics may have public health implications for designing outreach programs aimed at counseling and testing persons at highest risk of exposure to HIV. rovide risk 42 MR194 Sfondl'dlzod Scales and DocI-nfnflon of AIDS-HIV Knowledge and Provmlon for Health Care Professlonuls and the Pub”: HARVEY S. BMW ID, UCSF School 0' Medlclne and AVE“. AIDS VIrus Emma and Rmroh Ins1l1u1e, Sen Franclsco. CA The eplde-Ic of AIDS and Hulnn lI-uodeflclency Vlrus (HIV) lnfecflons present-s new problems In mlng health care proioulonels and the publlc- These problems Include: (I) rapld mulled-Ion of blwedlcel Infmlon whlch may be relevant to clInIoul pfoc‘l’loa; (2) new concepts In pathoblology spoclflc to HIV lnfec+lonsz (3) phoblc blocks sssocls1od wah groups at hlghlr rlsk whlch lay preclude unblesod esslnlloflon of Iniormlon on HIV; and (A) the characfsr of an expendlng colds-Io whlch Increeslngly affects senv espec+s of soclefy. Due To fhese Issues, fradlflonnl loans of oduceflon re Inadequate to deal with the Modesty dlsse-Insflon o! lnforneflon on HIV. In nddlflon, a lock of sfenderdlzeflon of AIDS Information My enhance nlsoonoepflons. faclllfm false Inlmlon. nnd Madly Mac? Ira owl-cl cllnlcal care of paflen? wlfh AIDS or ARC. Mlsconcspflons and false lnforneflon on AIDS wIII only spread the oplde-Ic even are. AVERI, AIDS Vlrus Educeflon and Research Insflfuve, was founded In I984 to deal wlfh these Issues- AVEII provlde: oduceflonel prof-s about AIDS for various sectors of the putllc and oohflnulng oducnflon about AIDS and HIV for heelfh care professlonels- Also, AVERI. In conjuncflon wl+h If: Medical Advlsory Board. has devised three sfunderdlzed scales to documenf esslmlllflon of AIDS Infernaflon. No one (lay or physlclnn) should be provldlng counsellng or educeflng others sbouf AIDS wlfhouf e passlng score on one of the scales. The first ls 'B__AP_S." anlc AIDS Prevenflon Scale, la” the lay publlc- Second I: 'AAPS.‘ Advanced AIDS Frevenflon Scale. for health care professlonals and heelfh care employees. For health care provssslonals frosting AIDS and ARC pnflenfs. the-e ls I'AAPl‘S.‘ Advanced AIDS Prevenflon and Treatmenf Scale. In the oplnlon of the AVERI Medlcal Advlsory Board. 851 of all hosplfll personnel should schleve n passlng score on 'BAPS' and all hosplfal and pre-hosplfal heslfh care professionals should be able to pass 'AATS' If nof 'AAPTS.' Hid-spread use of These 3 test scales. along wlfh qusllfy AIDS~MIV educeflon will decrease the spread of fhe epIde-Ic. dea'eese AIDS phobles. and opflmlze care of the AIDS paflen‘h MR195 Psychological Reactions of Indlvlduals at Risk for AIDS Participating in an Experimental Drug Trial PAUL B. JACOBSEN*, s.w. PERRY**, R.B.ROBERTS**,*Memorial Sloan-Kettering Can- cer Center, New York, NV,**The New York Hospital, New York, NY. Administratlon of anti-viral agents has been proposed as a means of preven- ting the development of AIDS In asymptomatic Individuals infected with HIV. However, since these individuals typically feel physically well and, In addi- tion, may be psychologically dlstressed because of their risk status, there Is concern about their willingness to adhere to an experimental drug trial. The present study addressed this question by studying 26 homosexual/blsexual males enrolled In a randomized double-blind trial of ribavirin. Subjects were with- out manifestations of AIDS or ARC, but were HIV antibody and viral positive. Standardized self-report measures of psychological distress (Brief Symptom Inventory) and perceptions of treatment were administered during the first 2 weeks of the drug study and, again, 8 weeks later near the end of treatment. Results indicated that mean levels of distress at the Initial assessment were 2 to 3 standard deviations above norms for the general population but were similar to norms for psychiatric outpatients and for other populations at risk for AIDS. Analysis of variance showed that mean levels of distress remained unchanged between the initial and follow—up assessments. In addition, T-test comparisons demonstrated that the intensity of distress at both baseline and follow-up was unrelated to patients' beliefs about whether they were receiving active drug or placebo. None of the 26 patients refused to continue partici- pation in the drug trial during the period of study. These findings suggest that, while asymptomatic seropositive individuals may remain psychologically distressed, they are likely to continue to adhere to placebo-controlled trials of anti-HIV drugs. MR196 Physician Attitudes and Stigma Associated with an AIDS Diagnosis JANET S. ST. LAWRENCE*, JEFFREY A. KELLY**, HAROLD V. HOOD**, STEVE SMITH, JR.*, & DONNA J. COOK*, *University of Mississippi, Oxford, MS and University of Mississippi Medical Center, Jackson, MS, **University of Mississippi Medical Center A randomly—selected sample of 163 physicians practicing in three cities (Co- lumbus, OH, Memphis, TN. and Phoenix, AZ) were subjects in a study assessing attitudes towards AIDS. These cities are the largest in states which rank near the midpoint for AIDS prevalence. Each physician/subject read a SOO—word vig— nette describing a male patient; vignettes were identical except that the patient's illness was identified as either AIDS or leukemia and the patient was identified as either homosexual or heterosexual. Subjects completed ob- jective measures assessing attitudes toward the patient after reading a ran— domly-assigned vignette. Multivariate ANOVAs showed that AIDS patients were considered more responsi- ble for and deserving of their illness, dangerous, deserving quarantine, and less deserving of sympathy (all p < .05 to p < .0001). Physicians reported markedly less willingness to interact with an AIDS patient than an identically- described leukemia patient in such contexts as conversation (p < .01), working in the same office, living in the same apartment building, attending a party, or continuing a past friendship (all p < .0001). As HIV infection prevalence increases outside the nation's largest cities, physicians in all practice specialities will see many more HIV patients. Health-care providers may share some of the same attitude prejudices as the general community. There is a need to develop better psychological/education programs for health-care providers especially in areas where AIDS prevalence will soon increase. MONDAY, JUNE 1 ME197 An AIDS Training Program for Mental Health Professionals ROSEMARY T, MOVNIHAN*, R. MCFARLANE*, G.H. CHRIST*, R. SAMET**, D. BECKHAM*, S. RICHARDSON***, *Memorial Sloan—Kettering Cancer Center, **Department of Mental Health, ***Gay Men's Health Crisis, New York, NY. An AIDS mental health training program was developed in 1986 through a col— laborative effort of New York City Department of Mental Health, the Memorial Sloan-Kettering Cancer Center Department of Social Work and the Gay Men's Health Crisis. To date, over one thousand professionals from voluntary and municipal hospitals, community mental health centers, social service agencies and chemical dependency units have participated. An initial needs assessment revealed that generic information about the med- ical and psychosocial aspects of AIDS was not sufficient. Substantive areas identified for training included: fears of contagion; countertransference issues relating to homophobia, aversion to treating drug addicts, feelings of hopelessness and helplessness, and emotional overwhelm or bereavement; work with the medically and terminally ill; coping with the enormity and intensity of patient needs; maintaining updated medical information. Five additional substantive areas were requested; drug addiction, minority culture issues, neuropsychiatric issues, family and relationship therapies. Pre-intervention evaluation revealed that participants had high levels of knowledge of AIDS which were not significantly increased through participation in the program. Positive change was observed at the end of the training in the following areas: 73% reported more optimism in helping PMAs cope with their illness; 75% reported greater empathy for PNAs; over 80% indicated they were more confident of their AIDS knowledge; over 80% were more aware of the psychological and medical needs, and over 60% indicated increased confidence in their ability to deal with value and lifestyle differences with patients. MR198 Control of Hypersexuality in HIV Carrier CLETO DI GIOVANNI*, F. BERLIN**, *Metropolitan Psychiatric Group, Washington, DC, * MThe Johns Hopkins Hospital, Baltimore, MD. A homosexual man with AIDS Related Complex sought psychiatric treatment be- cause of anxiety associated with hypersexuality. He reported that he had un— protected sex with as many as 40 anonymous partners weekly in bath houses; he said he recognized the health hazard to himself and others posed by his behav- ior but could not control his sexual drive. He gave written consent to weekly intramuscular injections of medroxyprogesterone acetate, which rapidly and profoundly lowered his testosterone level and reduced his sexual urges. He also received supportive psychotherapy and antidepressant medication, with marked mood improvement. Side-effects of the anti—androgen included mild hy- pertension that required antihypertensive medication. This case report suggests that a subset of HIV carriers who remain sexually promiscuous may have an atypical paraphilia that is responsive to combined psychotherapeutic and pharmacologic measures. MP199 Support Groups for HIV Positive Women Including Those With HIV Positive Infants. BRIDGET WAGNER, GREENBERG R, HIGGINS B, NORRIS H, TAYLOR J, UCSF, San Francisco General Hospital, San Francisco, CA, USA Epidemiological studies suggest that at present the seroprevalence rate among sexually active heterosexual women in the San Francisco Bay Area is between 0.596 and 5%. A need was felt in 1985 to create support groups for HIV positive women. Initially these efforts were unsuccessful. In September, 1986 the Women's AIDS Network tried again to establish support groups for HIV positive women. As of January, 1987 one group for HIV positive women has been established in San Francisco, and several other groups are forming including one for seropositive transexuals . This poster is planned to share our experiences: A. Establishing groups for HIV positive women: planning effective outreach strategies and addressing the importance of anonymity and confidentially. B. Group structure and client issues found to be effective. C. Addressing different needs for different clients i.e., women who have by vertical transmission infected their children as opposed to single women with multiple partners, or IV drug users. The psychosocial needs for HIV positive women are complex and often different from homosexual men. Support groups can help provide problem—solving, educational, and emotional support, and at the very least "a safe place" to share experiences in order to reduce feelingscf isolation. 43 "£200 Psychiatric Illness in HIV-Infected Men 5. Controls IGOR GRANT, C. J. KENNEDY, D. D. RICBHAN, S.A.SPECTOR, J A.. HCCUTCEAN, San Diego VAHC 5. UCSD School of Medicine, Ln Jolls, CA. USA. Psychiatric complications in hospitalized patients with acquired immune deficiency syndrome (AIDS) and AIDS—related complex (ARC) are widely reported, but little is known of the lifetime psychiatric history of ambulatory men with AIDS, ARC, or of asymptomatic men infected with HIV (human immunodeficiency virus). Lifetime prevalence and current psychi- atric disorder in nan infected with HIV, or at risk for infection were examined using the Diagnostic Interview Schedule (DIS, Version III-A), Profile of Mood States (POMS), and Symptom Checklist-90 (SCL-90). examined four groups of homosexual men and a comparison group of hetero— sexual men equated for age and socioeconomic status. The groups were (1) AIDS (N-lS); (2) ARC (N-l3); (3) Other HIV seropositive (“-16); (5) HIV seronegative (N-ll); and (5) seronegative heterosexual (N-ZZ). Results: Among all homosexual men (Groups l-h) lifetime prevalence of any DIS psychiatric disorder was 80.21; major depression was 30.41; alcohol abuse/dependence 32.11; other substance abuse 39.31; and anxiety disorder (excluding phobias) 39.3%. There was no significant difference between groups of homosexual men in prevalence of major syndromes. Over 30.31 of men in Groups l-k experienced the onset of s DIS—disorder within the previous six months. Group 5 subjects had markedly lower proportions of major depression (10 I) and anxiety disorder (01). Conclusion: Because lifetime and recent prevalence of psychiatric disorder among ambulatory men infected or at risk for infection with HIV is elevated, longitudinal assessment and early psychiatric intervention may improve patient care. MR201 Behavior by Intravenous Drug Users that Can Transmll HIV. AS ABDUL-QUADER‘. SFI FRIEDMAN'. Dc DES JARLAIS", M MAFIMOH'". Fl MASLANSKY‘"'.S BARTELME'". et at. ‘Naroollc and Drug Research Inc. “NYS DIV 01 Substance Abuse Svcs. "'NY University Med Center. ""Bellevus HospitalNY In New York. Intravenous drug users (IVDU) are the maln source of HN transmlsslon b other IVDU and to heterosexual partial and mm transmission AIDS cases. 195 Manhattan methadone patients were inlervlewed In 1986 about drug Injection. sexual behavlors and child-bearing plans. They had moan lrequencles of 22 drug Injecfiom per month, of whloh 4.7 were in shoollng galleries; they knowingly Isl others use lhelr used syrlnges a mean of 6.6 limes per month. 125 male sublecls each had mean total sexual frequency of 6 times per momh with a mean ol1.8 female partners. On average, each man had .6 1391;13:sz purifiers who were not IVDU. 61 female subjects each had mean total sexual frequency of 11 limes per month wllh a mean of 2.7 male partners. On average. each woman had .6 mule! sex partners who were no: IVDU. 59/153 (39%) subjects Inland to have further children. 49% of 165 subjects Ior whom Abbott ELISA and Westsm blot HIV antibody test results were available were seroposlllvo. Subjects who had been In melhadone Irealrnenl for more lhan 24 monlhs had greatly and significantly lower frequenolos of drug-related transmission behavlor than lhoso In neahnonl for lesser perlods, although they did not dIllor slgnilloanlly In sexual behavlors that can transmit HIV. Drug“, ' ' ‘ were ‘1'“ as- T m5(p<. 0001); Inlecuon In shooting galleries 12/mo. as compared to .84 (p<. 007); and the frequency of knowingly Ionlng others use works Ihey had already used was 17/mo. as compared b .76 (p<. 0005). 39% ol 28 women In resonant more than 24 months Intended I) bear future ohlkken. as compared to 69% of 16 women In usehnent two years or less (p<.06). IVDU frequently behave In ways Ihal can usnsmll HIV 0) other persons. Methadone treatment appomstbnxhcssuchdnnlnkxfionbohawkxs Sinsnmmhadonspaflemssngagelnconfldembw potenlially risky sexual behsvlor, AIDS education In such uaahnont programs should Include oounseIIng about heterosexual and Imam transmlssbn nlpzoz Psychosomatic Distress and Depressive Symptoms Among ' HTLV III/LAV Seropositive, Seronegative, and untested Homosexual Men SUSAN D. COCHRAN, California State University, Northridge, CA _—REEWT33§E—3f—HTLV III/LAV infection is sometimes advocated as a means to encourage behavior change. However, such knowledge can also have a negative impact on psychosocial functioning. The cur- rent study examined levels of common somatic complaints and de- pressive symptomatology in a sample of 150 gay men, none of whom had been diagnosed by a physician with AIDS or ARC. The sample was divided into three groups: those who reported positive HTLV III/LAV blood testing results, those who had been found to be negative, and those who had not had a blood test and did not know their HTLV III/LAV infection status. Men indicated the presence or absence of 15 common somatic complaints, 10 were consistent with early ARC or AIDS symptoms and 5 contraindicated an ARC or AIDS diagnosis. Men also completed the CBS—Depression Scale. Results indicated that the men who tested positive reported sig- nificantly more somatic complaints. more AIDS—related complaints and greater levels of depression than either men who tested nega- tive or who had not been tested. They also showed a trend to report more AIDS-unrelated somatic complaints. Men who tested negative and those who had not been tested did not differ signifi- cantly from each other on levels of somatic complaints or depres— sion. Results suggest that knowledge of a positive HTLV III/LAV result may have negative consequences for psychosocial functioning, but a negative result does not lead to less distress than not knowing. MONDAY, JUNE 1 MB203 Patterns of Heterosexual Contacts Among Intravenous Drug Abusers; Implications For the Heterosexual Transmission of the Human Immunodeficiency Virus DEBRA L. MURPHY*, L.S. BROWN, JR.**, B.J. PRIMM*, *Addiction Research and Treatment Corporation, Brooklyn, NY, **Harlem Hospital Affiliate of the Columbia College of Physicians and Surgeons, New York, NY. There is a scarcity of knowledge about the sexual behavior pat— terns of the intravenous drug abuser (IVDA), despite the poten- tial role of this group in the heterosexual transmission of AIDS. Using a representative sample of 100 clients of the Ad— diction Research and Treatment (ARTC), who consented to be anony— mously interviewed, this study investigated sexual behavior pat- terns in this sample of intravenous drug abusing clients. Chi square analyses indicated that at the .001 level of significance, IVDA males were more likely than IVDA females to report heterosexual contacts which were non—IVDAs. Further, among those most likely to have been exposed to AIDS, either by reported needle sharing and/or sexual contact with other intravenous drug abusers, gender was associated with the number of non—IVDA heterosexual contacts at the .001 level of significance. These findings were supportive of other studies which have suggested the potential for an epidemic spread of the AIDS virus among non-IVDA females with IVDA partners. MP204 Use of the "Needle Guard" in the Prevention of Needle— stick Injuries. PAUL N. GOLDWATER*, A.D. NIXON**, R. LAW**, J.0FFICER***, J.F. CLELAND***; ’The Adelaide Children's Hospital, North Adelaide, South Australia, **Auck1and Hospital, Auckland, *** The Medical Laboratory, Auckland, New Zealand. The "Needle Guard" system was evaluated during a 21 month period during which 454,000 venepunctures were performed. It was shown that "Needle Guard" users incurred a needlestick once in every 23,546 venepunctures, whereas, non—users of the "Needle Guard" incurred an accident once in every 4,929 venepunctures (p<0.001). This 79.9 percent reduction in needlestick accidents attributable to the "Needle Guard" calls for a review of the non-recapping guidelines issued by the Centers for Disease Control. MP205 The AIDS Epidemic: A Projection of Its Impact on Hospitals, 1986-1991 JESSE GREEN, Ph.D., M. SINGER, MPH, N. WINTFELD, Ph.D., New York University hbdical Center, New York, NY The AIDS epidemic in the United States will have a dramatic impact on the health care delivery system, especially hospital facilities. By 1991, 12,831 hospital beds in the U.S. will be occupied by AIDS patients, more than by lung cancer patients or automobile accident victims. In San Francisco, one of every 10 hospital beds and 19 cents of every dollar spent on inpatient and outpa- tient therapy will go to treatment of AIDS. In New York, bed need for AIDS will nearly triple from 645 beds in 1986 to 1,753 beds by 1991. In the rest of the country outside these cities, the level of hospital utilization by 1991 (1.14% of beds and 3.2% of treatment costs) will be close to what is being experienced in New York City today. The impact of AIDS on hospital facilities goes beyond these numbers. AIDS patients require added infection control pre- cautions, nursing care, supplies, and complex case managenent services. Per» haps the most difficult challenge is to face the task of treating young pa- tients with a ravaging disease without the ability to offer a cure. Dr. Green served as consultant to the Institute of Medicine, National Acadrny of Science‘s Task Force on a National Strategy for AIDS. This paper was pre~ pared as background for the Institute‘s report, Confronting AIDS » Dirggtigps for Public Policy, Health Care, and Research. Utilization of Nurse Practitioners in the SFGH AIDS Clinic. BARBARA J. BRODIE, G. CARR, San Francisco General Hospital AIDS Clinic, San Francisco, California, USA. MP.206 The rapid expansion of the outpatient AIDS clinic at San Francisco General Hospital required an increase in primary health care providers. Nurse Practitioners were added to augment the medical staff, and have an expanded role within the clinic. During most clinic sessions both physicians and nurse practitioners see patients. Nurse practitioners carry their own caseload, guided by protocols and working in consultation with clinic physicians. Two clinics are run solely by the nurse practitioners. One is for studying and monitoring investigational drug trials. The second is a unique AIDS screening clinic, developed in response to a growing concern by an increasing number of high risk individuals, who have no prior diagnosis of ARC or AIDS. After formal clinic sessions, the nurse practitioners remain available for medical backup, to provide coverage for assessment and triage of emergencies and for telephone consultation. This is a presentation of a descriptive paper addressing the expanded nurse practitioner role within the AIDS clinic, the advanced knowledge needed, and how guidelines and protocols for nurse practitioner practice were developed to meet the needs of the clinic. MR207 and prevalences in a Danish sample. JENS J. PINDBORG, JUDITH RINDUH & MORTEN SCHIODT. Dental Department, Universi- ty Hospital ("Rigshospitalet"), Department of oral Pathology, Copenhagen, Den- Oral manifestations of HIV infection: Suggested EEC classification mark. On 16—17 September 1986 the EEC convened a meeting in Copenhagen on oral problems related the HIV infection. During the meeting a tentative classifica- tion of 31 oral lesions in patients infected with HIV was agreed upon. The classification divides the lesions into fungal, bacterial & viral infections, neoplasms, and lesions of unknown etiology. Previously infections with Candida albicans have been called oral candidiasis or oral thrush. However, there is a need for dividing candidiasis into pseudomembranous, erythematous and hyper- plastic types. In the past a number of the erythematous type of candidiasis have been overlooked. The classification has been applied to 130 HIV infected patients at the University Hospital of Copenhagen. Of these patients 38 had AIDS, 16 ARC and 76 were just seropositive. Sixty-eight percent had one or more oral lesions considered associated with the HIV infection. Candidiasis was found in 41%, hairy leukoplakia in 37% and necrotizing gingivitis in 10%. M2208 Multiple Funding Sources for Comprehensive AIDS Public Health Services RICHARD CONVISER, Ph.D. and S. YOUNG, New Jersey State Department of Health (NJSDH), Trenton, NJ. The population most seriously affected by AIDS in New Jersey consists of IV drug addicts, their sexual partners and children. Because this population has limited financial resources and political/community support, and because federal funding for public health services is limited, the NJSDH has had to take the lead in providing services. The Department's role has been to provide seed money to develop and implement programs while identifying other long-term funding sources to support ongoing service delivery. A key element in the Department's strategy has been an increase in drug abuse prevention and treatment. The Department has sought to substitute a continuum of alternative care services for lengthy stays in acute care facilities. Funding for the alternative cars has been sought from a variety of aourcssv—atats, federal, private (Robert Wood Johnson) foundation, and Medicaid. Effective use of the resulting mix of funds requires creative administration. Federal and state funds support specific projects and personnel in unit projects; those from the private foundation support in-hospital case management, post- hospitalization services, and education. Supplemental funds from the state support direct services not reimbursable elsewhere. The Medicaid waiver supports home/community care for individuals as an alternative to hospitalization. A matrix will correlate the funding mix with the continuum of services planned by the stats. MONDAY, JUNE 1 M2209 Influence of disease and casemix severity on the hospital costs of caring for AIDS patients. by Mary M. Fanning, T. Harmon. F.A. Shepherd, H. Vellend. S. Minnick. Dept. of Medicine, University of Toronto and Travenol Management Services, Deerfield, Illinois. The estimated total cost of medical care for a patient with AIDS varies considerably among several published studies and may reflect differences in efficiency of care, disease severity of the hospital case mix as well as accounting practices. Seventy-four percent of all AIDS admissions to Toronto General Hospital between January 1983 and December 1985 were classified into five diagnostic categories: simple Kaposi's sarcoma (S-KS), complex KS (C-KS). simple Pneumoc stis carinii pneumonia (S-PCP), complex PCP (C—PCP), and Central Nervous System disorders (CNS). The average cost per admission was calculated by methodology used by Travenol Management Services. Costs were lowest for S-PCP (SCanadian 11,822) and S-KS ($12,020) and increased for the other admission diagnoses: CNS ($15,716), C—KS ($18,045) and C-PCP ($26,395). Daily hospitalization costs also varied among the groups: S-KS and C-KS - $560/d, S-PCP $630/d, CNS $700/d and C-PCP $906/d and all were greater than the average hospitalization costs for non—AIDS patients. Incremental costs of caring for a patient with AIDS compared to a non-AIDS patient were at least 31% greater and led to a net loss to the hospital. Admission diagnoses over the course of illness varied considerably among patients categorized as KS or PCP at initial diagnosis. Case mix changed over the observation period with increased severity of disease and costs. A forecasting formula was derived and demonstrated the influence of observed and projected changes in case mix severity on total yearly hospital costs for AIDS patients. Strategies for cost containment will be discussed. MP210 AIDS/ARC Patients in Residential Drug 'I‘reatment Therapeutic Camiunities: A Special Program JOYCE JADGCN, G. KDRIGJEZ, R. BAX‘I'ER, S. NESHIN, N.J. State Dept. of Health (NJSDH), East Orange, NJ In New Jersey, where Iv addicts comprise the majority of AIDS cases, many patients contiame to use drugs after diagnosis, have no stable living arraxgenmts, and are tm—ccmpliant with medical regimen. They continue to transmit HIV by needle-sharing, sexual contact and perinatally. This paper describesaneffortbyfiieNJSDHtoaddresstheseissuesbyproviding funding for 30 beds in 5 residenfial drug treatment therapeutic oanmmities for AIDS/ARC patimts. Programs were oaitracted to provide 1) daily RN cmtact, 2) weekly physician contact, 3) 5 hours MA level therapy weekly, 4) nutritional , 5) prescribed medications and supplies, and 6) transportation and liaison with AIDS treatment facilities. Patients were referred by l'nspitalsarxiotheragezciestoNJSDH, wherereoordsweresmeenedand patients placed. To be eligible, patients must be ambulatory and capable of self-care, alert and oriented, and willing to accept a structured residential envizumei'it. By January 1, 1987, out of 60 referrals, 30 patients had been successfully placed. Problais have included cooperation of referral scuroes, referral of nursing hare level patients, patient acceptance of awirutnent, program willingness to modify concept and practice to accamodate social, psychological, and pharmacological needs of AIDS patients. MP211 Chronic Care for AIDS Patients: The Health And Hospitals I Corporation Model for Long Term Care PAUL A. MOORE, H. RICHARDSON, NYC Health and Hospitals Corporation, N.Y., N.Y. The NYC Health and Hospitals Corporation, a: the largest provider of hospital care to AIDS patients in the country, cares for the many patients who remain hospitalized after medical clearance but for whom post acute care placements are not available. About half of this population is homeless, the remainder are certified for some form of long term care Skilled Nursing Facility (SNF) or Health Related Facility (HR!) cars. HHC is currently providing long term can to a number of such patients in "chronic care" beds at two of its facilities. Key elements of this service modality are explored: referral and assessment, intensity of medical care, relationship with acute care facilities and cost/revenue issues. 45 nnE212 The Adequacy of Hospital Reimbursement for AIDS Patients JOHN S. CLARK, D.B. McCallum, Institute for Health Policy Analysis, Georgetown University Medical Center, Washington, DC. Hospitals are having to balance the competing forces of cost containment efforts by third party payors with increasing numbers of AIDS patients who require particularly costly treatment. Reim- bursement to hospitals for AIDS patient care has important finan- cial consequences for hospitals and patients, and could affect quality and access. An analysis of 169 AIDS admissions between 1982 and 1986 at two hospitals in Washington, DC explored the proportion of hospital costs met by various payors and the efficacy of DRG reimbursement for AIDS patient care. ‘ Preliminary results suggest that commercial insurers (64 cases) paid approximately 24% above estimated cost, while Blue Cross/Blue Shield (40 cases) paid at about cost. The percentage of cost paid by Medicaid (15 cases) differed substantially between admissions, but surprisingly the vast majority fell between 5% below and twice the estimated cost. Those who are without insurance (17 cases) were able to pay only 5% of the cost of treatment, suggesting that hospitals have a strong incentive not to admit these patients. DRGs in which AIDS patients are commonly placed could result in the under-compensation of hospitals (eg. DRG 398) or over-compen- sation (eg. DRG 79). This suggests that if third party payors a- dcpt DRG based reimbursement strategies in the future, or if AIDS patients become Medicare eligible, DRGs frequently used for AIDS patients will need to be adjusted, or new DRGs specifically de- signed for AIDS patients be created. MP213 Foster Care Needs of Children with HIV Infection MARY BOLAND, M. TASKER, P. EVANS, E. CONNOR, J. OLESKE Children‘s Hospita of New Jersey & UMD-New Jersey Medical School, Newark, NJ Children with perinatally acquired HIV infection are members of multiproblem families. 0f 50 families with 57 children, 17.50 (42%) of the families were known to the family protective agency (New Jersey Division of Youth & Family Services [DYFS] prior to the diagnosis of HIV infection. The families were referred for neglect (3/17), abuse (2/17), and foster care placement (12/17). In addition, 3/50 families were referred after diagnosis for neglect (l/3) and placement support services (2/3). 21/57 children are in foster care because of the following: death of a parent (4/21), illness of a parent (2/21), and ina- bility or unwillingness of the parent to care for the child (15/2l). Identi- fying a foster home or facility willing to care for a child with AIDS is difficult. Placement within the extended family occurred for l5/21 children and 6/21 children were placed in DYFS approved foster homes. A11 placements were maintained although extensive support to the foster family was required once the child was diagnosed. Extended family members require education about the disease as well as ongoing social and financial support if the placement is to be successful. Human services agencies must be willing to care for these children. Health care providers must be available to inform prospective foster parents about the disease and assist foster parents deal with the health care system. MR214 Prevalence of Human Immunodeficiency Virus (HIV) Antibodies in Prostitutes and their Clients in Addis Ababa, Ethiopia. SEYOUM AYEHUNIE”, S. BRITTON**, TEBEBE YEMANE-BERHAN***, T. FEHNIGER”. KDepartment of Biology, Addis Ababa University, **Armauer Hansen Research Institute. ***All Africa Leprosy Rehabilitation and Training Centre (ALERT) Hospital, Addis Ababa, Ethiopia. To determine the prevalence of antibody reactivity against HIV infection we studied 230 subjects, 60 prostitutes and 70 male clients who were seen at three local clinics because of venereal disease complaints, and 100 control subjects from the out-patient department of ALERT. Out of the 230 study subjects 4 female prostitutes, 2 male clients and 1 from the control subjects were found to be positive by the Organon ELISA test. However, when the confirmatory test was done by Western Blot assay only the 4 prostitutes and 1 male client were sero ositive showing reactivity to HIV polypeptide antigens of P24, P34, 31.)“, P5 , P64, gplzo in molecular weight. These sera were retested and confirmed positive by the State Bacteriological Laboratory in Sweden. This limited seroepidemiological study has determined seropositive individuals without clinical disease within the Addis Ababa geographical region. The low number of seropositive individuals within the population tested suggests a more recent establishment of HIV infection within this high risk behaviour group than in equivalent studies of prostitutes and sexually active individuals reported from other geographical regions of Africa. MONDAY, JUNE 1 M2215 The Rising Demand for Hospital Beds by AIDS Patients and the Fiscal Implications for Globally Budgeted Hospitals STEVEN A.GROVER*, L. COUPAL*, N. GILMORE**. *Department of Medicine, Montreal General Hospital, **Division of Clinical Immunology, Royal Victoria Hospital, McGill University, Montreal, Quebec, Canada. To evaluate the growing demand for hospital beds by AIDS patients, we ana- lyzed the hospital utilization rates of AIDS patients followed at the Royal Victoria Hospital (RVH) from 1981-1986. As of December 31 1986, 79 AIDS pat- ients have bgen treated and 65 (82%) have been hospitalized resulting in 138 admissions (x = 2.1 adm./pts.). while the number of AIDS patients diagnosed each year has increased 14.5 times, the annual admission and inpatient occu- pancy rates have increased approximately 29 times. During the same period, the total number of available medical beds has remained constant. YEAR TOTAL 1981 1982 1983 1984 1985 1986 CHANGE-(1986-81)/81 New Cases 79 2 3 4 14 25 31 14.5 Admissions 138 2 4 5 21 45 61 29.5 Hospital Days 3512 61 124 242 274 962 1849 29.3 Mean Stay 29.1 30.5 31.0 48.4 13.1 21.4 30.3 Our'data indicate that the growth in demand for hospital beds by AIDS pat— ients has exceeded the rise in the number of cases treated at the RVH. In 1986, 2.81 of all medical beds were occupied by AIDS patients. Should this trend continue, AIDS patients will significantly increase the competition for scarce hospital beds. This increased demand for hospital resources will be further compounded if AIDS patients require more services in hospital than the average non-AIDS patient. Fixed global hospital budgeting, as practiced in Quebec, will not be able to respond to this change in case—mix and demand for services unless precise coating of the services used by AIDS patients is undertaken and health care planners respond appropriately. M2216 Ampligen Therapy for HIV Related Immunodeficiency. HORACE F. HENRIQUES*,G.L. SIMON**,D.R. STRAYER#,W.A. CARTER#,L. EINCK+,R.S. SCHULOF**. Departments of Medicine** and Surgery* George Washington University, Wash.,D.C. 20037,Department of Neoplastic Diseases#,Hahneman University Phila., PA. 19102,HEM Research,Inc.+ Rockville,MD 20852. Ampligen, a mismatched dsRNA which inhibits HIV replication in vitro,was given to eleven HIV infected patients with ARC or AIDS to study the anti—viral and immunomodulating effects of this drug. There was no drug toxicity or side effects seen. Seven ARC patients received 200mg twice weekly for 12-16 weeks and 5 were then placed on 100mg twice weekly as a maintenance dose. Four AIDS patients received 250mg twice weekly and this dose was maintained in 2 and doubled in 1 based on clinical response measured at 8 weeks. All patients were HIV culture positive and anergic by multiple skin tests at the start of the study. All patients demonstrated reversal of skin test energy within 8 weeks. Lymphadenopathy resolved in 3/5 patients. In one patient both hepatospleno— megally and psrotid enlargement resolved with Ampligen. Chronic oral candidiasis resolved in another patient. One patient developed PCP for the second time and died after 7 weeks of therapy. No other AIDS related events were noted. In 9/11 patients there were changes in viral parameters: 1/9 became negative by lympho- cyte co—culture,P24 antigen concentration decreased in 2/5. In 7/8 mRNA levels and in 7/10 HIV polymerase concentrations decreased. T4 levels improved in 3 and stabilized in 8 patients. After 6 weeks of maintenance therap» patients remain asymptomatic with intact DTH responses and no change in T4 levels or T4/T8 ratios. The clinical improvement noted in these patients paralleled the apparent viral suppression. These promising results and the absence of drug related toxicity,support the use of Ampligen in additional trials in HIV infected patients. MR217 Intravitreal Ganciclovir (BW B759U) in the Management of Cytomegalovirus Retinitis FRED M. USSERY, III, s. GIBSON, R. CONKLIN, n. PIOT, E. STOOL, et 31. Park Plaza Hospital Special Diseases Unit, Houston, Texas Eight patients with unilateral or bilateral CMV retinitis associated with the acquired immune deficiency syndrome were admitted to a protocol designed to evaluate the efficacy of Ganciclovir (BW E759U) administered by the intraocular route. All patients had been treated previously with intravenous Ganciclovir; however, thrombocytopenia and/or leukopenia had necessitated the interruption of intravenous therapy. In each case, two hundred micrograms of BW B759U dissolved in 0.1 m1 Balanced Salt Solution were injected into mid—vitreous through the pars plans under ophthalmoscopic visualization, with retrobulbar anesthesia. Careful attention was directed to minimizing the likelihood of introducing bacteria into the vitreous, to the maintenance of blood flow through the retinal vasculature, and to rapid normalization of intraocular pressure after the injection. Suppression of the retinitis was observed in seven of the ten treated eyes. Two eyes did not improve. One eye developed a retinal detachment as a result of the procedure. Of ten treated eyes, eight required reinjection within two to twenty days to maintain suppression of the retinitis. The optimum schedule for reinjection is currently unknown. The intravitreal route of administration of Ganciclovir is well-tolerated by the eye and is associated with reasonable success in suppressing CMV retinitis. It offers an alternative for maintaining vision in patients unable to tolerate intravenous Ganciclovir. M2218 Observations on Clinical and Immunologic Parameters in AIDS/ARC Patients Treated with IMREGQ-l A. ARTHUR GOTTLIEB, M.S. GOTTLIEB, C.H. KERN. Imreg, Inc. and Tulane Medical School, New Orleans, LA and Cambridge, MA, USA. Patients with AIDS or symptomatic ARC were enrolled in three studies of 16 patients each. Each group received IMREGO—l. an imaunoregulator derived from healthy human leukocytes, as follows: Group A: Once every four weeks, subcu— taneously; Group B: Once every two weeks, subcutaneously; Group C: Once every two weeks, intradermally. The purpose of these studies was to determine if IMREGw—l could be safely administered in multiple doses, and to follow changes in immune parameters and clinical indicia of these parameters in these patients during treatment. Delayed hypersensitivity to tetanus toxoid returned or increased in 47, 57 and 752 of patients, while the average number of T4+ cells increased or were unchanged in 31, 44 and 812 of patients in groups A, B and C respectively. T4+ (helper) cells increased by 422, 362 and 561 in the 5, 7 and 12 individuals of each group that demonstrated increases in T4+ cell number. During the treatment period there was no observed toxicity attributed to the drug. No new opportunistic infections or deaths were observed, while patients were on protocol. Hematologic parameters appeared to stabilize. Resistant candida infections responded to treatment. Some patients gained weight, while in others there was no weight loss. We observed a decrease in serum uric acid and immunoglobulin levels which may reflect decreased white blood cell de- struction and modification of excessive non-specific B cell function. A Phase III randomized placebo control clinical trial in symptomatic ARC and recent onset Kaposi's Sarcoma patients is in progress and will enroll 150 patients. Each patient will be followed for six months of treatment or until an endpoint is reached. MP219 Evaluation of Antitrypanosomal and other Antlparasltlc Drugs in the Therapy of Experimental Pneumoc stls carinil Pneumonia (PCP) PETER D. HALZER***, C.K. Kim***, J. Fog/“1:, Fl. Hendrix‘". M.J. Linke***, M.T. Cushion***, VA Medical Center*, U. C1ncinnatl**, Cincinnati, OH. New drugs are needed for the treatment of PCP in AIDS. We have conpared antiprotozoal agents with other antlparasltlc drugs in the treatment of experlmental PCP. Rats were given corticosteroids for 8 weeks to induce PCP. The drugs were administered during weeks 5-8, and therapeutic efficacy was judged by examining lungs for PC using a semiquantltatlve histologlc scoring system in formalin fixed sections and counting organlsms in lung homogenates. Cation1c antitrypanosomal agents were the most active conpounds: dimlnazene, 1midocarb, amicarbalide, quinapyramine, and 1sometamidlum had efficacy 3 that of pentamidlne, the standard drug; guanylhydrazone and ethidium bromide also showed some activity. Efficacy and toxiclty of these drugs were related to dose and route and duration of administratioe. With successful treatment, PCP sc re gnd counts fell from 4+ (heavy) and 10‘/lung to 0-l+ (neg-light) and 10 -10 /lung. The following drugs showed little or no activity agalnst PCP: quinine, quinidine, qulnacrlne, pentostam, chlorpromazine, splramycin, pentostam, and astlban. The data suggest that drugs used in the treatment of a veterinary African trypanosomiasls are highly act1ve in the therapy of experimental PCP. Since efficacy in the rat model has usually been predictive of success in humans, these compounds represent a new therapeutic approach to PCP with important potential clinical application. MRZZU Effects of DHPG on Severe Cytonegalovirua Infection in AIDS SA Danner” JKM Eeftinck Schattenkerk. OHE Visser, KW Slaterus Depts of Medicine, Ophthalmology and Virology. Academic Hospital at the University of Amsterdam. The Netherlands. Cytomegalovirus (CMV) infection counts for much morbidity and mortality in AIDS. DHPG, a new acyclic nucleoside analogue of guanine has good antiviral effects against CMV in—vitro. We studied efficacy and safety of DHPG, 2.5 or 5.0 mg/kg body weight i.v. during 14 days, in clinical CMV infection in AIDS patients, CDC classification system IV—C or IV—D. Diagnosis of CMV infec— tion was made on the combination of virological, histological and clinical grounds. A DHPG course was given 20 times in 18 patients for: retinitis (11 cases), pneumonia (5), colitis (3) and spinal cord infection (I): in 3 addi- tional patients diagnosis of CMV pneumonia could not be confirmed virologi— Cally; these cases were included for safety analysis only. Virological re- sults: CMV positive urine and throat cultures became negative in 13 out of 15 patients within 14 days of treatment, and again positive after cessation in 5 out of 7 evaluable patients, mostly within 3 weeks. Clinical results: the spinal cord infection didn't improve, colitis responded well in 2 out of 3, pneumonia in 2 out of 5 and retinitis in 7 out of 11 cases. Retinitis re- lapsed within 4 weeks after cessation of therapy, so maintenance therapy, 2 times a week 5.0 mg/kg i.v. was instituted with good effect. In 3 patients DHPG was given intravitreally, 0.4 mg per 14 days in order to avoid frequent hospital visits. Results are promising and a pilot study is under way. Thrombocytopenia was seen 3 times (requiring drug withdrawal in 1 case), mo- derate leucopenia in most cases. reversible after drug cessation. le conclu— de that DHPG is a relatively safe and effective drug in CMV infection in AIDS patients, especially in colitis and retinitis. However, relapse prophy— laxis is needed and platelet and white cells counts should be monitored. MONDAY, JUNE 1 IflP221 Randomized Prospective Trial of Ganciclovir Maintenance ' Therapy for Cytomegalovrius (CMV) Retinitis Mark A. Jacobson*, HR Brodie*, JJ O'Donnell*, CC Nofsy*, J Mills* ‘UCSF School of Medicine and S.F. General Hospital, San Francisco, CA. We report the first randomized prospective comparative study of long-term maintenance ganciclovir therapy for CMV retinitis in patients with AIDS. Eleven CMV retinitis patients who received a ten day course of ganciclovir induction therapy were randomized to receive either immediate daily ganciclovir maintenance therapy or deferred maintenance (8 deferred maintenance, 3 immediate main- tenance). The two groups were well—matched for prior history of Pneumocystis pneumonia (PCP), visual acuity, mean age. Karnovsky score, hemoglobin, platelet count and neutrophil count at onset, as well as follow-up (4.8 vs. 5.1 months). Median time to retin- itis progression was 42 days for the immediate maintenance group compared with 16 days for the deferred maintenance group, (p= 0.07, Z-tailed log rank test). After crossing over to maintenance therapy, patients in the deferred group had a median time to retinitis progression of 58 days compared to 16 days while not on maintenance therapy (p=0.13). Only 9% (10/107) of cultures obtained while patients received maintenance therapy were positive for CMV, versus 40% (8/20) of those obtained off maintenance (p< 0.001). For these 11 patients, median survival following diagnosis of CMV retinitis was 7 months. Nine of these 11 also had a history of PCP, with a median survival following PCP diagnosis of 8.5 months (not different from historical controls without CMV retinitis). This randomized comparative trial documents that maintenance therapy with ganciclovir delays progression of CMV retinitis and suppresses CMV shedding in AIDS patients, as compared to untreated controls M2222 PHASE I TRIAL OF RECOMBINANT GRANULOCYTE-MACROPHAGE COLONY STIMULATING FACTOR IN ACQUIRED IMMUNODEFICIENCY SYNDROME ASSOCIATED LEUKOPENIA. J Groopman, R Mitsuyasu, M DeLeok, R Donahue*, D Oetcek, D Golde, et al. New England Deaconess Hospital, Harvard Medical School, Boston, MA; Genetics Institute, Cambridge, MA; Sandoz Pharmaceuticals, East Hanover, NJ; and UCLA School of Medicine, Los Angeles, CA. The granulocyte—macrophsge colony stimulating factor (GM-CSF) is a glyco— protein with a variety of in vitro activities including potentiation of myeloii colony growth and stimulation of leukocyte function. Because of the frequent decreased number and function of leukocytes in AIDS we performed a phase I study evaluating safety and efficacy of GM-CSF. Recombinant GH—CSF (s.a. - 4.4 x 106U/mg protein) was administered at doses of 1.3 x lO3U/kg/d, 2.6 x 103U/kg/d. 5.2 x lO3U/kg/d and 1.0 x IOI'U/kg/d to groups of 4 patients at each dose. A single IV dose was followed by a 14 day continuous IV infusion All patients were men with total peripheral WBC 3,500/u1. The drug was well tolerated with mild symptoms of headache, myalgia, and nausea. Increased liver function tests occurred in 3 patients. Recombinant GM-CSF was active in vivo with elevations in mean peripheral NBC from baseline to day 15-17 of 1850 to hS75/ul (at 1.3 x 103U/kg/d), 2675 to 8650/ul (at 2.6 x IO3U/kg/d), 1900 to 8743/..1 (at 5.2 x 103u/kg/d), and 2600 to 17,300/u1 (at 1.0 x lOI‘U/kg/d). No significant change in hemoglobin or platelet count was seen. The increase in "BC was mainly due to neutrophils, bands, and eosinophils with a two four-fold increase in total monocyte and lymphocyte counts. 2—10 days after discontinua- tion of drug the NBC returned to near baseline. Recombinant GM—CSF is active in leukopenic AIDS patients, well tolerated, and may have a clinical role as a single agent or in combination with antiretroviral therapy. MP223 Efficacy of BWASISU in Treatment of EBV Infection in Hairy Leukoplakia DEBORAH GREENSPANt, l& GREENSPAN’, Y.DE SOUZA*, SK. CHAPMAN”, E. LENNETTE'”, and V. PETERSEN‘, *University of California, San Francisco, CA, "Burroughs Wellcome Co., NC, and ***Virolab lnc., Berkeley, CA. We investigated the effects of BWASISU, a potent acyclovir prodrug, on the clinical features and viral components of oral hairy leukoplakia (HL), an AIDS-associated lesion. We have previously shown the presence of EBV in fully replicating form in the lesion of HL using cytochemistry, electron microscopy and DNA hybridization. Fourteen patients with HL, none of whom had AIDS at the time of the study, were assigned to drug or placebo groups on a randomized double blind basis. 250 mg of BWASISU or placebo were taken orally t.i.d. for 1!: days. Clinical photographs were taken at 0, 7, 114 and 28 days. Biopsies were performed at day 0 from HL lesions and at day 14 from lesions or from the site of lesions where they disappeared. 7/7 patients on active drug showed significant or complete resolution of the lesion clinically, while 7/7 receiving placebo showed no change. Histological features of HL significantly diminished in patients on active drug, while cytodiemical and ultrastructural studies showed elimination or dramatic reduction of EBV infection in the active drug group only. This study shows that BWA515U was effective, on a short-term basis, in eliminating the clinical, histological and virological features of oral hairy leukoplakia. Supported by Burroughs Weilcome and the University of California Systemwide Task Force on AIDS. y 47 Anti-CMV Treatment with DHPG Does not Affect HIV Antigen Levels in AIDS Patients. MP.224 JOHANNES GAUB", 3.0. LINDHARDT***, A.-G. POULSEN", C. PEDERSEN“, C.M.NIEL$EN****, . e al., Depts of Infectious Diseases. *Rigshospitalet and **Hvidovre Hospital, **** State Serum Institute, ***The Fibiger Institute, Kobenhavn, Dannark. In a study of the anti-HIV effect of foscarnet in 15 patients with AIDS, HIV antigen was found in 8 before treatment, and it disappeared temporarily during and after treatment in 5 of these. Four of the 5 patients had positive CMV culture prior to foscarnet treatment, but negative cultures during and after therapy. PROBLEM: Since foscarnet is effective against CMV as well as against retroviral reverse transcriptase, its effect on HIV antigen could be secondary to its effect on CMV, which may be a co-fector in AIDS development and progression. DESIGN: We have studied HIV antigens in sera from 8 patients with AIDS and CMV chorioretinitis, treated with DHPG (Syntex) for 14 days. RESULTS: DHPG was effective against CMV clinically and virologically. Seven patients had HIV antigen in serum. HIV antigens did not change during DHPG treatment. CONCLUSION: The effect of foscarnet on HIV antigen levels is probably indepen- dent of its anti-CMV effect. M2225 Dose Response Study of Diethyldithiocarbamate (DTC or Imuthiol) in Patients (PTS) with ARC and AIDS. EVAN M. HERSH, E. PETERSEN, D.E. YOCUM, R.S. GORMAN, J.M. DARRAGH, University of Arizona Health Sciences Center, Tucson, AZ USA. In previous study, DTC at a dose of 200mg/M2 was shown to significantly improve symptoms and signs of ARC and AIDS and was shown to induce a trend towards improved prognosis. In the current study pts. with ARC or AIDS were randomly allocated (after stratification for ARC vs. AIDS, E vs. >2 symptoms, 5 vs. >200 peripheral blood T lymphocytes per m3) to receive or not receive DTC for 16 weeks followed by a cross over to the other treatment arm on which they were again treated or not for l6 weeks. Pts. received DTC 200mg/M2 intravenously (IV) weekly (0N)x4 wks then 400mg/M2 (IV) 0N x4 wks, then 800mg/M2 (IV) on x4wks, then 800mg/M2 twice weekly x4wks. Doses of 200 and 400mg/M2 were non—toxic. Doses of 800mg/M2 either once or twice per week were toxic, inducing chest pain and dyspnea, nausea and vomiting, fever and skin rash. Thus far l9 pts. have been randomized, ll to treatment and 8 to control. Of these, 2 treated and 6 control have progressed. The treated patients progressed after 4 and 15 weeks of treatment. The treated pts. had P. Carinii pneumonia (PCP) while the 6 controls had Kaposi's sarcoma (2 pts.). PCP (2 pts.), M. avium intracellulare (l pt.) and severe progressive weight loss (3l lbs. over 3 months) withdebililation (performance status, Zubrod, declined from I to 4) (1 pt.). Evaluation of blood counts, blood chemistries, T cell phenotypic markers, lymphocyte blastogenic responses to the mitogens PHA, PNM, CONA, and delayed hypersensitivity to recall antigens showed no major changes except that 8/ll treated and 1/8 control pts. showed an increase in Tll + cells at 8 weeks. Thsse results indicate that the maximally tolerated IV dose is >400 and <800m /M . The apparent difference in prognosis sug ests that further controlled studies in larger numbers of pts. are warran ed. M2226 OI‘IO J. PLESCIA“, D. Pontani**, C. Schaffner“, D. Sun***, P. Sarin***, and S. I. Shahied“, *Waksman Institute of Microbiology, Rutgers-The State Univer sity of NJ, New Brunswick, NJ, MNew Jersey State Department of Health, Trenton, NJ, ***Laboratory of Tunor Cell Biology, NCI, Bethesda, MD. Central to AIDS is the progressive loss of T4 helper cells by the cytopat'hic action of HIV, dependent on replication of the virus in infected cells. Virus- infected cells are a reservoir of virus that can spread to other normal T4 cells. Our strategy to control infectious HIV is based on three objectives: (1) inactivate extracellular virus directly, (2) inhibit replication of HIV in virus-infected cells, (3) increase the resistance of T4 cells to infection by HIV. AME, a relatively non-cytotoxic methyl ester derivative of Amphotericin B, binds to sterols in manbranes of cells and lipidenveloped viruses such as HIV. In cultures of H9 test cells infected with HIV, AME (l to lOuM) inhibits viral replication, thus protecting H9 cells against HIV, and prevent: the spread of virus fran virus—infected H9. AWE also prevents the spread from virus- infected lymphocytes of AIDS patients. Based on results of pretreating HIV, virus-infected H9 cells, and normal H9 cells with AME, it meets all three of our objectives. Clearly AME inactivates HIV, and in combination with Foscarnet, an inhibitor of viral reverse transcriptase, it is more effective because of synergism Biological response modifiers are also candidates as synergistic drugs. (mr results provide a rational basis for using a combina- tion of synergistic drugs for the treatment of AIDS. Treatment of AIDS Based on a Combination of Synergistic Drugs MONDAY, JUNE 1 Treatment of ARC Patients with Sodium Diethyldithiocarbamate (DTC, M2227 ImuthiolR). A Multicentric, Randomized, Double Blind, Placebo con- trolled Trial Members of the AIDS-IMUTHIOL FRENCH STUDV GROUP (Lyon, Paris, Strasbourg, Tours), France. This study was designed to evaluate the clinical efficacy, inmunorestorative potential and tolerance of Imuthiol in the treatment of ARC patients. Patients were selected for presence of constitutionnal symptoms and T4 cell numbers below 600/cu mm. They were randomized to be treated with either Imuthiol (10 mg/kg, once a week, oral route) or placebo capsules. Asof January1987, 92 patients entered this study. After 4 months of treatment improvement of the clinical status was observed in 42 % of evaluable Imuthiol treated patients while 55 % were stable and 3 % worsened. In placebo group, only 8 % improved while 86 % were considered as stable and 6 % worsened. Pro- gression to AIDS occured in 5 out of 36 placebo treated patients, but none in the Imuthiol group (N = 33). Weight loss or splenomegaly disappeared in all Imuthiol treated patients who presented these symptoms on day 0. After 4 months, 42 % of the Imuthiol treated patients had T4 cell numbers over 600 cu mm. Recruitment of more than 350 additionnal T4 cells per cu mm over the 4 month treatment was seen in 30 % of the Imuthiol treated group. This trial will be completed before the meeting and results discussed. M2228 In Vivo Anti-Retroviral Properties of Recombinant Alpha Interferon in AIDS with Kaposi's Sarcoma and Healthy HIV- Seropositive Homosexual Men JOSEPH KOVACS*, H.C. LANE*, H. MASUR*, B. HERPIN*, J. FEINBERG**, A.S. FAUCI*. *Nationa institutes of Health, Bethesda, MD, **Scher1ng—Plough, Kenilworth, NJ. Alpha interferon is a leukocyte derived glycoprotein with anti-viral, anti-proliferative and immunomodulatory effects. It has been shown to be clinically effective in the treatment of AIDS—related Kaposi's sarcoma (KS) in 20-40% of patients and to have in vitro activity against HIV. The present study was designed to determine the in vivo anti-retroviral activity of recombinant alpha interferon in 30 AIDS patients with KS in an open trial of 35 million units of interferon daily and in 60 asymptomatic HI culture positive homosexual men with more than 400 CD4+ lymphocytes/m in a placebo controlled trial. At this time 15 KS patients and 20 asymptomatic individuals have entered the study. Of the 9 evaluable KS patients, 5 have had a complete or partial anti-tumor response (mean CD4 count for responders = 445 vs. 101 for non-responders). Reductions in HIV-isolation were noted in 3/5 of the KS patients with an anti—tumor response and 0/4 of the non-responders. 0f the 10 evaluable asymptomatic HIV infected individuals 4/5 interferon treated and 1/5 placebo treated patients became culture negative during study. Although the current sample size is too small to draw firm conclusions, it appears that alpha interferon may have in vivo activity against the AIDS virus. MR229 Survival of the Human Immunodeficiency Virus Under Controlled Drying Conditions on a Hard Surface. SHERRY L. LOSKOSKI, L.S. MARTIN, W.W. BOND, Centers for Disease Control, Atlanta, GA. we determined the stability of the human immunodeficiency virus (HIV) (LAV prototype strain) after drying and storage under controlled temperature and relative humidity (RH) using the ID—SO and antigen capture assays. HIV in culture fluid (0.1 ml, ID-50=103) was placed on 1/2-in2 stainless steel strips, and the strips were dried for 2 hr at 25.6°C and 282 RH in a vertical laminar-flow safety cabinet. Strips were then stored at 25°C in a desiccator jar over a saturated aqueous solution of potassium carbonate (enclosed RH=42Z). We removed triplicate strips from the jar at intervals of 1,3,5, and 7 days and assayed for viable virus. At each interval, 0.1 ml of media was added to each strip for 10 minutes, and the eluent was assayed for viable virus. A liquid control was performed in parallel. The virus titer eluted from the strips was reduced approximately 1 log during iniital drying, followed by a more gradual reduction over 7 days. The HIV titer held in the liquid state also dropped markedly. These results indicate that, although there is a 90% or greater reduction in titer after drying, HIV will survive drying and storage for a period of time. Survival after drying may effect future disinfectant chemical testing with this virus. 48 MP230 Variation in the Humoral Immune Responses of Rhesus Monkeys ' (Hacaca mulatta) Immunized with Formalin—Inactivated Type D Retrovirus Vaccine and Correlation with the Clinical Disease Outcome W, J.D. mum, 14.3. GARDNER“, and P.A. moor, *California Primate Research Center and **Department of Medical PathOIOQY, University of California, Davis, CA, USA. As part of a vaccine trial, six healthy juvenile rhesus monkeys (Kacaca mulatta) were immunized with a formalin—inactivated whole SAIDS type D rhesus retrovirus serotype—l (SRV—l) vaccine containing the adjuvant threonyl muramyl—dipeptide. Following immunization, all six animals showed antibody response against viral core and envelope proteins. The pattern of antibody response in immunized animals was unchanged in response to chal- lenge with a potentially lethal dose of SRV-l. All immunized animals were protected from persistent viremia and remained clinically healthy. Two of six non-immunized control rhesus which received adjuvant alone, developed antibodies against core and envelope proteins following live virus chal— lenge and exhibited only transient viremia. Four additional control rhesus failed to develop detectable antibody post-challenge and succumbed to simian immune deficiency syndrome (SAIDS). Variations in antibody response of individual immunized animals were observed even though all received identical viral proteins. These dif- ferences may reflect the titer of antibody made by these animals to specific viral proteins. This study demonstrated that early development of specific virus—induced antibodies correlated with a favorable clinical outcome. MR231 Experience in Treatment of Idiopathic Thrombocytopenic Purpura (IT?) in HIV-positive Homosexuals by Perfusion of Plasma over Staphylococcal Protein A-silica (Prosorbao Columns). HARRY W. SNYDER, JR., J. BERTRAM‘, F.R. JONES and the PROSGRBRD CLINICAL TRIAL GROUP. Angeles, CA. ITP is an autoimmune disease frequently found in association with HIV infection in homosexual men. In ITP platelet-associated antibodies (PAA) and/or circulating immune complexes (CIC) bind to platelets (Plt) and accel- erate their destruction by the reticuloendothelial system. Recently a clinical trial was conducted to evaluate removal of FAA and CIC from plasma of ITP patients by perfusion through columns of protein A—silica. Twenty- four patients were evaluated after receiving 4—8 treatments involving absorption of 250 ml plasma. The patients presented with 5026 x 103 Plt/mm’ and elevated PAA and CIC. During treatment Plt counts in 14 patients in- creased 1.6-4.3 fold (mean: 2.5:0.3, P=0.04). Coincident with this effect were drops in PAA (3229 ng IgG/los P1t to 1014 ng) and Clq-CIC (105123 ug/ml to 60:15 ug/ml, P=0.14). Responses of 4 of these patients were transient ( <2 weeks duration), while ther responses in 6 of the other 10 patients were of greater than 6 months duration. Plt counts continued to rise in these patients 1.3-4.5 fold (mean: 2,310.5) after termination of treatment. Plt counts and FAA and CIC levels were not altered in nonresponder patients. Serological parameters which were predictors of positive responses to treat- ment were PAA >10 ng/lo6 Plt (P=0.04) and Clq-CIC >60 ug/ml (P=0.04). The results suggest that extracorporeal removal of IgG antibody and CIC from plasma modulates the autoantibody response and decreases Plt destruction. IMRE Corporation, Seattle, WA and USC Cancer Center, Los MP232 The Lookback Program in a High-Prevalence AIDS Region ' STEVEN KLEINMAN AND K. SECORD, American Red Cross, Los Angeles, CA. The lookback program has been designed to locate, inform, and test persons who received blood components prior to anti—HIV test— ing from donors who were later found to be anti-HIV(+). Our pro- gram provides anti-HIV testing, physician education, recipient counseling and spouse testing if requested. We have identified 513 potentially infectious components donated from June 1983 to March 1985 and have thus far located 282 recipients of whom 163 (58%) expired during hospitalization. The anti-HIV(+) rate in 53 living recipients was 77% when tested 18—42 months post transfusion; this rate did not vary over 3 seven month periods beginning in 6/83. We have not yet observed a case in which recipients from 2 con— secutive donations by the same donor have been anti—HIV(—). Also, in one case, a unit of rho was split and given to 3 infants: 2 tested anti-HIV(—) but one tested anti-HIV(+). These findings of a) a high infectivity rate of lookback donors, b) discordantanti- HIV results in recipients of the same donation, and c) the diffi- culty of obtaining anti-HIV results from recipients ofconseéutive donations lead us to recommend notifying lookback recipients as quickly as possible, rather than on a case by case basis. Coun- seling sessions with 19 anti-HIV(+) recipients have been vital in helping these persons to understand and cope with the information. Anti—HIV testing of 12 spouses (6 male, 6 female) has been nega- tive despite 1 to 3 years of continued sexual contact with the anti—HIV(+) recipient. Anti-HIV testing and counseling services will increase the public health benefits of lookback programs. MONDAY, JUNE 1 MR233 Anti-HIV Testing of Blood Donations in the United Kingdom HAROLD H. GUNSON and V.I. RANLINSON, Regional Transfusion Centre, Manchester, Eng and. Routine screening of blood donations for anti-HIV which commenced in the U.K. in October l985 has been performed principally using the Nellcome competitive ELISA test. Donors are informed that the test will be carried out and asked to sign their agreement. Those confirmed anti-HIV positive are informed and counselled. By the end of October l986 approximately 2.8 million donations have been tested and 6l (0.002%) were confirmed anti-HIV positive. Of the 59 anti-HIV positive donors interviewed to date only 6 deny belonging to a recognised risk group with respect to HIV infection, the majority comprising young homosexual or bisexual men and intravenous drug abusers. Approximately 320,000 persons donating blood for the first time have been anti-HIV tested and l5 (0.004%) have been confirmed as positive. All those interviewed have admitted to being in recognised risk categories. The majority of anti-HIV positive donors attend- ing for blood donation did so because they did not consider that the self- exclusion categories specified in the leaflet issued to all donors applied to them since their homosexual activity or drug abuse had terminated several years ago. A revised leaflet has now been issued to donors in an attempt to resolve such misunderstandings. . Four confirmed anti-HIV positive donors had been tested previously. One was found to give repeatedly equivocal results and the donation was not used. of tmrm“thMflfMMamhMVmwfiwomishwnmhwehdmswm conversion following transfusion of products from the donation to two patients. ME234 Inhibition Enzyme Inmunoassay for Determination of Anti—HIV Specificity NRAPENDRA NATH, C. HUNDERLICH, C. FANG, R.V. DODD, American Red Cross, Jerome H. Holland Laboratory, Rockville, MD Only a small proportion of donor blood found repeatable reactive in currently available commercial enzyme immuno assays (EIA) is specific for anti—HIV when tested by Western blot (NB) assay. NB assay is subjective and prone to technical variation and is therefore not suitable for routine use as a confirmation test. He have developed an Inhibition EIA that utilizes biotinylated human IgG anti-HIV and an antigen coated solid phase from Abbott or Genetic System tests for anti-HIV. The Inhibition EIA is based on competition-inhibition format and is designed to be used in the field in conjunction with the commercial test in use for screening of donors. Using Inhibition EIA we successfully identified as positive 53 of 55 NB positives and also found 64 of 65 NB negatives as nonreactive. NB negative samples included 32 that were repeatably reactive in Abbott EIA. We tested additional 166 specimens that were repeatably reactive in Abbott EIA but demonstrating atypical or "indeterminant" band patterns in WB. Only 1 was found reactive in Inhibition EIA. This sample was later found to be HB reactive on retest. Inhibition EIA is a simple, objective and reliable substitute for HB for routine determinantion of anti-HIV specificity. MP235 Removal of human immunodeficiency virus (HIV) by ultrafiltration YOSHIAKI HAMAMOTO*, SHINJI HARADA*, NAOKI YAMAMOTO*, HIDEKI IIJIMA**, SEI-ICHI MANABE**, HIIZU AIZAWA**, *Department of Vi— rology and Parasitology, Yamaguchi University School of Medicine, Yamaguchi, Japan, **Asahi Chemical Ind. Co. Ltd., Osaka, Japan We intend to propose a new method to remove HIV perfectly from a desired solution such as plasma. As a filter, the regenerated cellulose membranes having various mean pore sizes were prepared from the cupurammonium solution of cellulose through the micro— phase separation method. After the filtration of HIV preparation with these membranes, we evaluated the infectivity of HIV in both filtrates and filtrants through the'assays for HIV-induced cyto- pathic effect (CPE), immunofluorescence method for expression of HIV-specific antigens and a plaque assay for quantitation of bio- logically active virus using MT-4 cells. When the pore size of the membrane determined by the water filtration rate method was smaller than 30 nm, neither CPE nor fluorescnet cells were detect- ed in MT—4 cells cultured with the filtrates five days after cul- ture, whereas in the cells with filtrants, remarkable CPE was observed and all cells were fluorescent three days after culture. Moreover, under such filtration conditions, no plaque was formed with the filtrates although the titer of HIV in the filtrants showed 106 level of plaque-forming units per ml. In addition, the novel porous polymeric membrane was found to scarcely absorb protein molecules. 49 ”“2236 Traps of HIV—Serology: Independent Changes in Sensitivity and Specificity of ELISA Kits GEORGE FUST,E.UJHELYI,M.HEJJAS,S.R.HULLAN, National Institute of Haemafo ogy and Blood Transfusion,Budapest,HUNGARY As a National Reference Laboratory for blood donor screening and transfusion—related HIV-infection, we have tested 1374 serum samples for the presence of HIV antibodies. More than 150 repeat- edly ELISA positive samples were found by us or sent to us for control. But of them, anti—HIV positivity could be confirmed IFA and/or WB tests in 39 samples.118 samples, however, were found to be false-positive. Using deep-frozen aliquots of these sera, we have compared sensitivity and specificity of different batches of 6 different commercial anti—HIV ELISA kits. A mathe— matically—evaluated serum dilution method was used for the sensi— tivity measurements.lwo types of changes were observed at repeated determinations: a.) a significant inter-batch and even inter—box sensitivity difference was found with some kits, relative sensi— tivity of the different kits also changed, b.) reactivity of the plates for true—positive and false-positive sera independently changed among different batches of the same kit: while reactivity for true—positive sera was constant, a significant decrease or increase in reactivity for false-positive sera were found. These observations point to poor reproducibility of some commercial kits which can cause serious difficulties in screening labora— tories. by MR237 Evaluation of an Anti—HIV Screening Test Using HIV 311 Specific Synthetic Oligopeptides RICHARD S. SMITH*, M. HANSON**, D. BOSCH**, H.F. POLESKY**, *Johnson and Johnson Biotechnology Center, San Diego, CA, **Memorial Blood Center of Minneapolis, Minneapolis, um. U.S.A. A research ELISA test in which microtiter wells were coated with synthetic peptides from the E region of the human immunodeficiency virus (HIV) was evaluated for accuracy. Serum samples previously tested for anti—HIV with licensed ELISA reagents and the Western Blot method were selected for testing with the 3:3 peptide assay. The assay detected 25/26 (962) samples that were repeatedly reactive (RR) by ELISA and confirmed anti-HIV specific (pZA and gplvl bands) by Western Blot. Two (2) patient samples that showed reactivity to the gplil band only were reactive on the e_nv peptide assay. of 35 samples from healthy individuals that were R by ELISA but reactive only with the p25 band on the E peptide assay 33 (94%) were non-reactive. The peptide assay correctly identified as negative>982 of 212 samples from blood donors who were non-reactive for anti-HIV by ELISA and Western Blot. These preliminary data indicate that the 33 specific peptide assay may provide a sensitive and specific alternative to ELISA screening tests which use whole viral lysate. M2238 Prevalence of Antibodies against Various Epitopes of Envelope 120,9p41) and GAG Proteins of HIV in AIDS Patients. TATJANA FRENKL*, E. HEIMER*, B. MCGHEE*, B. MALES*, M. USATEGUI*, R. POTTATHIL*, et al.**, *Hoffmann-La Roche Inc., Nutley, N.J., U.S.A. and **F. Hoffmann-La Roche & Co.; Ltd., Basle, Switzerland. Peptides corresponding to various conserved regions of envelope and gag were cloned and expressed in E, coli. Fusion peptides that contain portions of ga and envelope were also made. In addition, small peptides (10-30 amino acids) corresponding to various regions of gp 120, gp 41 and tat were synthe- sized by solid-phase peptide synthesis. Recombinant proteins and synthetic peptides were tested for their immune reactivity against normal sera (600 samples) and HIV antibody positive sera (597 NB+ samples). We have identified several highly antigenic epitopes of envelope ( amino acid sequences 58-68 and 487-511 of gp 120, 578-608 of gp 41), gag and tat that may be useful in early identification of HIV infection. Peptides corresponding to these antigenic epitopes were used as HIV antigen in an ELISA test for antibody. One of these fusion proteins showed 100% sensitivity and 100% specificity when used as HIV antigen in a bead-EIA test for HIV antibody developed at Roche. The data on a) purity of HIV peptides, b) antigenic epitope-analysis of gp 120 and gp 41 and c) development of a simple and accurate test for HIV antibody will be presented. MONDAY, JUNE 1 M2239 Effects of Drying on the Human Immunodeficiency Virus (HIV) Diluted in Heparanized Blood, Serum or Media. LINDA S. MARTIN, S.L. LOSKOSKI, Centers for Disease Control, Atlanta, CA. We assessed survival of HIV after drying the virus in tubes and in covered tissue culture plates. In both, drying required several hours. In the first, tubes containing 0.1 ml of virus in media were dried under vacuum in a desiccator and maintained dry until tested. ID—50 Ds AOC-Liguid Room te erature-Li uid Room temperature-Dried ‘Bl — 10 - 105-7 10 - 1 104.8 103.5 103.9 3 107.0 101.9 102.4 5 103.9 102.1 103.9 6 104.1 101.4 102.1 In another set of experiments, virus diluted in heparinized blood, serum (both negative for HIV antibodies) or media (RPMI +101 FCS, +102 1L2) was plated into 24 well plates, which were covered and allowed to dry overnight at room temperature (RT) or 37°C. The dried matrix was then rehydrated and the ID-50 titer determined. In 3 experiments, no virus was recovered after drying at 37°C. ID-SO before dryiggjafter dryingrat RT Matrix Exp.1 Exp.2 Exp.3 Media 10 - /10 ‘ 10 ' /10 - 10 0 /Not Done Serum 104-3/103-4 103-3/<101-o 103-°/<101-0 Blood 104-3/<102-0 105-°/ 25 months,and the on— set of ARC by 3 to > 24 months. At the end of the follow up period (January I987),15/16 patients with HIV an— tigenaemia had a ecreased number of l-helper/inducer cells in periphereal blood (< 0,5 x 10 /I).In contrast,on1y 7/17 patients without HIV antigenaemia had a decreased number of T—helper/inducer cells. In conclusion,the study indicates that the developement of AIDS or ARC in most patients with HIV infection is preceded by HIV-antigenaemia .Ihus,HIV an- tiqenaemia signifies active viral infection with resultant immunodeficiency, and later the onset of AIDS or ARC.This may be of importance,when patients are selected for treatment with antiviral agents. T.3.6 m P. PHAIR J. CHAN-l, C-B HN.LEMARK, H. NU, J. HJHIIKAR, lbrtlwestem Lhiversity Nadica School and Howard Brow Namrial Clinic, Chicago, IL, U.S.A. The framency of huian innunodeficiency virus antigenenia (HIVAg) was determined using plasma obtained at seniannual intervals (1984—1986) fmn 121 imosexml or bisexual nen enrolled in a proSpective study of the natural history of HIV infection. By design the study contained 38 participants persistently negative for HIV antibody, 23 seroconver- ters and 60 men seropositive at entry, including 27 who have developed AIDS. Plasra was assayed for HIVAg using a solid phase innunoassay aiploying beads coated with human anti-HIV (Abbott Laboratories, lbrth Chica , IL U.S.A.). 0f the 83 seropositive nen, including the 23 vbo seroconverted, 34(42% had HIV/Ag. The occurence of 11va was asso- ciated with a decline in concentrations of antibody to p24 as determined by intensity of precipitation bands seen on innumblots. 32(391) developed HIVAg when relatively synptan— free and within 2-22 nonths after entry, 22(26%) developed AIDS. 2(2.4%) subjects were HIV/59 positive after diagmsis of AIDS. Cnly 3 participants progressing to AIDS did not damnstrate HIVAg. HIVAg was not detected before antibody developed in hen with incident infection. Mean interval bemoan the first detection of HIV/’9 and diagnosis of AIDS was 315 days (range 56 to 688) in the 22 men with prior HIVPg (Cpl). lVean CD4 nurber at the first time of detection of HIVPg before the diagosis of AIDS was 311 oells/mn3 1164 (s.d.). i’ean CD4 counts in the 10 nen with HIVAg who did not develop AIDS (Sp 2) was 481 oells/rrm3 : 202 (p=0.03 vs Gp 1), and in seropositive hen without HIV/’9 (5p 3) 710 oells/rmr3 1 345 (p ( 0.0001 vs Op 1; p = 0.01 vs Op 2). The host cannon clinical finding in HIVAg positive nen was generalized lynphadenopathy (56%), although 35% of participants were asymtonatic and 26% had AIDS-related synutms at the tine HIVPg was detected. HIVAg cuimonl y predates the onset of the opportunistic diseases which define AIDS and is asso- ciated with severe CD4 depletion. HIV ANTIGENBflIA AND AIDS TUESDAY, JUNE 2 Virology—Antivirals 'l' 41 Activity of 2',3'-Dideoxynucleosides as Single Agents or in Combi- ' ' nations against Pathogenic Human T—Lymphotropic Viruses _IE Vitro. HIROAKI MITSUYA, S. MATSUSHITA, J.S. DRISCOLL, M. MATSUKURA, M-S. REITZ AND S. BRODER ET AL. National Cancer Institute, Bethesda, MD 20892. Purines and pyrimidines with the ribose moiety in a 2',3'-dideoxy-—configu— ration can significantly inhibit the in vitro replication of a wide range of retroviruses without inhibitions of the growth and functions of target cells. Dideoxynucleoside analogues including erythro-3'-azido-Z',3'—dideoxythymidine (AZT) can completely block the infectivity and cytopathic effect of HTLV-III (also called LAV or HIV) against T-cells under conditions of the substantial virus excess. Dideoxynucleoside analogues also block the i_n vitro infectivity of HTLV-I, which can cause a wide spectrum of diseases including adult T-cell leukemia, innuunodeficiency state, and neurological abnormalities. A variety of dideoxynucleoside derivatives have been tested for the activity against HTLV- III. For example, the antiviral activity of 5—f1uoro-2',3'-dideoxycytidine is as potent as its parent analogue, dideoxycytidine (ddC), while 5-bromo-, or 5- methyl—ddC is inert against the virus. In cells protected by dideoxynucleoside analogues the viral DNA synthesis and viral mRNA expression can not be detected. Dideoxynucleoside-S'—triphosphates strongly inhibit HTLV-III reverse transcrip— tase (RT) activity but much less mammalian DNA polymerase alpha activity. These 5'-triphosphates serve as substrates for the HTLV—III RT to elongate a DNA chain by one residue, after which the chain is terminated. In the case of ddc, the relative intracellular concentrations achieved i_n vitro exceed those needed for the DNA-chain termination. Combination of AZT and acyclovir shows a syner- gistic antiviral effect i_n vitro. Combination of AZT and dideoxyadenosine or ddC also shows a significant antiviral effect at low concentrations. These studies may provide leads in current attempts to develop regimens for effective chemotherapy against pathogenic human retroviruses. T.4_2 Inhibitory Effect of Various Reverse Transcriptase Inhibitors on Tumor Induction by Moloney Murine Sarcoma Virus _ig vivo MASANORI BABAX, R. PAquLsx, J. BALZARINI", 3. DE cumco’l and D.G. JOHNS” mega Institute for Medical Research, Katholieke Universiteit Leuven, B-3000 Leuven, Belgium, “Developmental Therapeutics Program, National Cancer Insti- tute, NIH, Bethesda, MD 20892, USA. Tumor induction by Moloney murine sarcoma virus (MSV) in newborn N'MRI mice is a representative model for retrovirus infection E vivo. Daily treatment with 3'-azido—2'.3'-dideoxythymidine (AzddThd) (125 mg/kg7day) protected more than 80 Z of the MSV-infacted mice against tumor formation and more than 90 1 against death. Even treatment with 25 mg/kg/day of AZT significantly delayed tumor formation, prolonged the life span, and protected 30 X of the infected mice against death. In contrast, treatment with either 125 mg/kg/day of 2',3'-dideoxycytidine (ddCyd) or 625 mg/kg/day of 2',3'-dideoxythymidinene (ddeThd) only resulted in a slight delay of tumor formation and no increase of survival rate. Mice treated with ddCyd at 625 mg/kg/day developed symptoms of acute toxicity, such as anemia, resulting in death within 10 days after the beginning of treatment. Combination treatment of ddCyd with deoxythymi- dine prolonged the life span and protected several of the infected mice against death. 2',3'-Dideoxythymidine (dd’l'hd) did not protect mice against tumor formation and death, even at a doaage of 625 mg/kg/day. Other reverse transcriptase inhibitors, i.e. suramin, Evans Blue and aurintricarboxylic acid, were also ineffective in protecting the mice against tumor formation and death at nontoxic doses. T.4.3 Anti-HIV Properties of Castanospermine. BRUCE D. NALKERM MARK KOHALSKI“. WEI CHUN GOH". LARRY ROHRSCHNEIDER **, WILLIAM A. HASELTINE***, JOSEPH SODROSKI*. Dana-Farber Cancer Institute, Dept. of Biochemical Pharmacology, Harvard Medical School, and ***H.srvard School of Public Health, Dept. of Cancer Biology, Boston, MA. **Fred Hutchin- son Cancer Research, University of Washington. Seattle. WA. Castanospermine (GAS, 1,6,7,8, tetrahydroxyoctahydroindolizine) is a plant alkaloid that has been shown to be a potent inhibitor of glucosidase I, and thereby prevents normal processing of glycoproteins. He tested whether this compound might inhibit the function of the HIV envelope in infection and cyto- pathicity. CAS dramatically inhibited syncytium formation in a transfected CD4+ cell line expressing the HIV fl gens. CAS effects on HIV replication were also examined using freshly HIV infected H9 cells treated with CAS. A dose-dependent protective effect was observed, as assayed by cytopathic effect, reverse trans- criptase activity. p24 radioimmunoassay, radioimmunoprecipitation. and virus yield. The effect was greatest at doses which did not significantly alter cell viability. CAS appears to exert its antiviral effects by alteration of the E glycoprotein and not by alteration of the CD1. molecule. Tlo-gp120 binding is not altered by CAS. but processing from gp160 to gplZO is decreased by this com- pound, suggesting that this is the mechanism of inhibition of syncytium forma— tion. Antiviral effects of CAS appear to result from a decreased virion infec- tivity due to inference with post-Tln-binding steps in virus entry, as well as a decrease in cell-to-cell virus transmission secondary to syncytium inhibition. Experiments evaluating possible synergistic effects of CA5 with other anti-HIV agents are currently underway. 54 T 4 4 Phosphorothioate Analogs of Oligodeoxynucleotidea: Novel Inhibitors ' ' of Replication and Cytopathic Effects of HTLV-III/LAV(Human Immo- deficiency Virus) _ifl vitro MAKOTO MATSUKURA*, K. SHINOZUKA", G. ZON**, H. MITSUYA‘, J-S. COHEN and S. BRODER‘, et al., *National Cancer Institute and “Wood and Drug Administra- tion, Bethesda, W) 20892 Nuclease-resistant phosphorothioate analogs of several oligodeoxynucleotides were tested i_n vitro for antiviral activity against HTLV-III/LAV on human T- cells. Two anti-sense sequences (lb-mots) complementary to the HTLV-III/LAV genome, a sense sequence, a random sequence, and homo-oligomera of dA and dC of two lengths (1A and 28-mers) exhibited a significant inhibitory effect on viral replication and cytopathogenicity under conditions of viral excess. The anti- viral activity was strikingly linear with 66 content; longer phosphorothioate analogs were more effective than shorter ones. None of the homologous sequences of unmodified normal oligomers, methylphosphonate analog, nor the 3-methylthy- mine containing phosphorothioate analog (the latter would be chemically blocked from binding to complementary sequences) showed any antiviral effects. The E novo synthesis of viral DNA was completely inhibited by 28~mer dC phosphoro- thioate at _>_ I»)! as assessed by Southern blot hybridization. However, even ZSuM of 28-mer dc phosphorothioate showed no significant inhibitory effect on the expression of p24 gag protein in chronically infected cells. These results sug- gest that the antiviral effect of phosphorothioate analogs of oligodeoxynucleo- tides is brought about by binding to certain viral component(s), possibly viral nucleotide sequences and thereby inhibiting d_e novo synthesis of viral DNA. We have also observed that lh-mer dc phosphorothioate synergistically enhanced the antiviral effect of 2', 3'—dideoxyadenosine. These data suggest that phosphoro- thioate analogs of oligodeoxynucleotide could be a novel class of therapeutic agent against acquired immunodeficiency syndrome (AIDS) and related diseases. T_4.5 Tumor Necrosis Factor—u and Interferon-y Have Anti—HIV Activity GRACE H.W. WONG*, J. Krowka**, D.P. STITES**, and D.V. GOEDDEL*, *Molecular Biology Department, Genentech, Inc., South San Francisco, CA, **Department of Laboratory Medicine, University of California, San Francisco, CA. One consequence of the defective immune response in patients with acquired immunodeficiency syndrome (AIDS) is an impaired synthesis of cytokines. The cytokines tumor necrosis factor—a (TNF—a) and interferon-y (IFN-Y) act synergistically to protect cells against HIV infection in vitro. In the presence of the two cytokines, expression of the viral antigen p24 and HIV RNA is dramatically reduced while levels of reverse transcriptase activity and production of infectious HIV particles are strongly inhibited. Combinations of TNF-u and IFN—y kill cells acutely infected with HIV and inhibit the production of full length genomic size of HIV mRNA in chronically infected H9 or HUT-78 cells. HIV infection does not induce the production of TNF-o or TNF-B mRNA, but HIV—infected cells are able to produce TNF mRNA in response to mitogens. T 4 6 QUANTITATION 0! THE HUMAN IMM'U'NODHICIENCY VIRUS IN PATIENTS ' ' TREATED WITH ANTIVIRAL AGMS SURAIYA RASHEED, RICHARD B. COOPER, AND SH", SU University of Southern California, School of Medicine, L.A., CA. Identification of HIV-infected cells and determination of virus titers directly in individuel's blood (i.e. prior to virus amplification) are critical factors in the prognosis and possible therapeutic intervention- of patients at risk to develop AIDS. We have developed an extremely sensitive fl situ hybridization method using molecularly cloned HIV-probe to quantitate the number of HIV infected cells prior to culturing fl vitro. combination of this method with short-term culturing and antigen detection assay, offers one of the most sensitive and specific systems to detect and to quantitate levels of viral RNA, reverse transcripts-e, proteins as well as cytopathogeniclty of HIV in patients at risk to develop AIDS. These techniques are particularly useful for comparison of the results before and after the treatment of patients with the drug. l’urthermore, antiviral effect- of various chemical compounds that are currently being used for clinical trials in HIV-infected individuals can be quantitatively assessed at the level of specific cell types that may be involved in the pathogenesis of AIDS. A TUESDAY, JUNE 2 Clinical Management—Neurology The Brief Neuropsychological Examination for AIDS Dementia Complex: T'5'1 Correlations with Functional Status Scales and Other Neuropsycho- logical Tests JOHN J. SIDTIS, HANNAH AMITAI, DONNA ORNITZ, RICHARD w. PRICE, Memorial Sloan-Kettering Cancer Center, New York, NY. The AIDS dementia complex (ADC) is a progressive syndrome that is a frequent complication of HIV infection. Although the natural history of ADC has not been fully characterized, experience with moderate and severe ADC has suggested that it shares features with the "subcortical" dementias. In order to better characterize the natural history of ADC as well as systematically assess the effects of antiviral therapies in multi-center studies, we have developed a brief battery of neuropsychological tests that are sensitive to some of the major features of ADC: motor slowing, poor concentration and reduced spontaneity. The tests include verbal fluency, Trail Making A, Trail Making B, digit-symbol substitution, finger tapping with dominant and non- dominant hands, and a timed gait test. Our initial experience with these tests indicates significant decrements in performance across patient groups with increasing severity of HIV infection ranging from asymptomatic HIV infection to AIDS. Moreover, in a series of 100 evaluations in over 60 AIDS patients, these tests correlated significantly with a number of function nnwsuhsmdeghmMHLKwuhaMBhsmSmhgam,mm importantly, with AIDS-specific neurological history and examination scales (correlations ranging from r = .4 to r = .8), and other neuropsychological tests including additional NAIS subtests, memory and motor tests (correla- tions ranging from r = .4 to r = .9). This brief battery constitutes a functionally significant core of tests that is suitable for inclusion in large population natural history and therapy studies. T 5 2 Neurologic and Neuropsychologic Complications of ' ' Lymphadenopathy Syndrome. ROBERT s JANSSEN*, A SAYKIN**, J KAPLAN*, T SPIRA*, P PINSKY*, L SCHONBERGER*. *Centers for Disease Control, Atlanta, GA, and **University of Pennsylvania School of Medicine, Philadelphia, PA, USA. To determine whether there is an association between neurologic and neuropsychologic abnormalities and human immunodeficiency virus (HIV) infection in lymphadenopathy syndrome (LAS), we studied 39 seropositive patients with unexplained lymphadenopathy for >3 months (mean duration of LAS=4.1 years) and 38 homosexual/bisexual men (controls) who were seronegative for HIV. Participants were evaluated with a neurologic symptom questionnaire, neurologic examination, a 5-hour battery of neuropsychologic tests, immunologic tests, and magnetic resonance imaging. Fifteen patients (381) with LAS had histories of symptoms of peripheral neuropathy and 9 (231) had a history of herpes zoster radiculitis. Overall, 21/39 (54%) patients and 3/38 (8%) controls had a history of symptoms or signs of neurologic abnormality (odds ratio=13.6; p<0.001). By neuropsychologic assessment, 9/18 (501) patients and 2/26 (82) controls were abnormal (odds ratio-12.0;p<0.002). Of those abnormal on the neuropsychologic assessment, the majority scored in the mildly impaired range. Magnetic resonance imaging was abnormal in one patient and one control. Neither neurologic nor neuropsychologic abnormalities correlated with absolute T-helper lymphocyte count or T-helper/T-suppressor lymphocyte ratio. These results indicate an association of neurologic and neuropsychologic abnormalities with LAS. They suggest that mild neurologic abnormalities in LAS are common and that HIV may be the cause. Cerebrospinal Fluid(CSF) Findings in HIV-infected Persons Without Clinically Evident Neurologic Disease Aflfl_Q‘QQLLIEB, R.w.Coomhs, B.Nikora, L.Corey, H.H.Handsfield, University of WA, Seattle, WA. USA. To evaluate the frequency of subclinical CNS infection with HIV, we performed cerebrospinal fluid(CSF) examinations and CSF cultures for HIV on 24 homosexual men with AIDs(post PCP without other active infections, mean age 36) and 10 subjects with persistent generalized lymphadenopathy(PGL, mean age 37). None of the 34 subjects had clinical symptoms or signs of CNS dysfunction. All AIDS patients had Karnofsky scares 370 and all PGLs had scores 280. Mean T4 counts were loo/mm and ssg/mm3 in the 2 groups; all AIDS and 3 PGLs had T4 counts <400/mm . All were HIV-seropositive. HIV was isolated from peripheral blood lymphocytes in all 34 patients. HIV was isolated from unfiltered CSF in 42% of AIDS and 50% of PGL subjects. CSF p1eocytosis(>5 WBC/mm3) was noted in only 3 of the HIV+ CSFs: 6 had CSF protein >40mg/d1. All CSFs had normal glucose values: none had detectable cryptococcal antigen or other viral pathogens. were no differences in any CSF, clinical, or immunologic parameters in CSF HIV-positive and negative subjects. HIV can be isolated in CSF from half of AIDS and PGL patients without constitutional complaints or overt neurologic symptoms or signs. The frequency of CSF HIV infection appears unrelated to the clinical stage of disease. The clinical significance of CSF HIV is unknown at present and requires further study. T.5.3 There 55 T.5.4 Cerebrospinal Fluid (CSF) Study in Forty—Four HIV—Infected patients: Clinical Correlation with Virus Isolation and Intrathecel Specific Antibodies Synthesis. Christine KATLAMA, M.A. REY, D. SALMON, P. NGOVAN, M. WOLFF, M.C. DAZZA H6pita1 Claude-Bernard, Paris, France CSF of 44 patients — 24 AIDS, 15 ARC, 5 asymptomatic - were studied for presence of HIV in culture and antibodies by Elisa. None had neurologic oppor— tunistic infections. Intrathecal HIV-IgG synthesis (2 Ab) was assessed on a ratio CSF-HIV x serum Alb : serum HIV x CSF alb 22. Presence of HIV was demonstrated by detection of reverse transcriptese activity in supernatant of cultures during 7 weeks. CSF characteristics and computerized tomography were recorded. 25/44 patients (57%) had neurologic disorders possibly related to HIV : encephalopathy (18), polyneuritis (3), meningitis (3) myelopathy (1), and 19 were asymtomatic. v o v o v 9 v o | EAb 0 ZAb G ZAb 0 ZAb 9 TOTAL | -Number of patients 13 5 22 4 44 —with possibly HIV neurologic disorders 8/13 5/5 12/22 0/4 25 l Prevalence of HIV infection was high (91% attested either by isolation of virus (41%) or specific antibodies intrathecal synthesis (50%). But this was not significantly associated with clinical evidence of HIV—nervous system involvement since 28% (5/18) of the patients with positive CSF culture and 45% (lo/22) of those with intrathecal antibodies synthesis were neurologically asymptomatic. These results suggest that the clinical signification of the presence of HIV in CSF remains unclear. T_5_5 The Clinical Spectrum and Time Course of HIV—associated "Aseptic" Menin itis HARRY HOLLANDER, S STRINGARI, UCSF Schools of Medicine and Nursing, San Fran- ClSCO, To better define the entity of HIV—associated meningitis, we reviewed the results of 80 consecutive diagnostic lumbar punctures in homosexual men with HIV infection t3 identify those with CSF pleocytosis. Twenty individuals had :6 cells per nm . Six of these had a secondary opportunistic infection docu- mented. Fourteen others had no secondary pathogen or neoplasm identified by CSF cultures or cerebral imaging studies. All 14 were either known to be HIV seropositive at the time of study or had prior manifestations of HIV disease, including 3 subjects with KS. None of the 14 had prior major opportunistic in- fections. Two patterns of disease were observed. Six men (group I) had acute onset of a self-limited illness characterized by headaches and fever, withne- ningeal findings in 3. One of 6 had a focal neurological deficit. Eight @roup 2) had a more indolent course. Seven had chronic headaches, no fever and no me- ningeal or neurological findings. One presented with cognitive dysfunction and ataxia but no headache. Mean values of CSF leukocytes and protein were higher in group 1 patients. Pleocytosis lasted for several months in 2 patients in group 2 who were restudied. CSF HIV culture was positive in 3 of 4 cases aud- ied. We conclude that HIV-associated meningitis occurs commonly and relatively early in the course of HIV infection compared to HIV encephalopathy. Headache rather than cognitive dysfunction is the most connmn clinical manifestation. The course can range from an acute meningitis to more low grade chronic sympto- matology. CSF inflanmation usually differentiates this condition from other HIV-associated neurological complication. HIV-associated meningitis does not mcessarily predict the development of otherHIV-related neurological syndromes. T 5 6 Polyneuropathies in Subjects Infected with HIV ' ' JEAN—ALBERT GASTAUT’, J.L. GASTAUT"; J.F. PELISSIER”*‘, J.B. TAPKO*, M. FINAUD, Y. CARCASSONNE*, et al., *Institut Paoli—Calmettes, Marseille, FRANCE, "* Hopital Saints—Marguerite, Marseille, FRANCE, "‘ Hopital de la Timone, Marseille. FRANCE. The neurotrophic effects of HIV are well documented. It can be directly or indirectly responsible for a wide variety of peripheral disorders and symp- toms. In order to detect clinical and infraclinical polyneuropathy we under- took a prospective study on the peripheral nervous system of HIV seropositive subjects (38 men and 2 women) with a mean age of 31 years (range 20 — 24). This population included 22 homosexuals, 13 drug addicts, 1 addicted homo— sexual and 4 bisexuals. Five were symptomless carriers, 13 had ARC and 22 had AIDS. All 40 patients underwent clinical neurological and electrophy— sical (E.M.G., motor conduction and sensitivity, F waves) examinations and sural nerve biopsy was performed on 23/40 (57,5 %). Peripheral neurologic anomalies, mainly quadridistal paresthesia, were noted in 18/40 patients (45 %). In 27/40 patients (67,5 %) clinical examina— tion revealed evidence of sensory neuropathy : especially distal hypoesthesia to bath and vibration and, less often, hypoesthesia to pin pricking and loss of Achilles jerk. Electrophysiologic data was more or less corroborative of exclusively or predominantly sensory polyneuropathy 33/40 patients (82,5 %) : midly lowered sensory motor conduction or greatly lowered action potentials and less often spontaneous denervation or prolongation of F wave latency. The results of 14/23 nerve biopsies are available. In 10/14 findings showed neuro— pathology involving axons (8 cases), myeline sheath (1), and circulatory im— pairment (1). Sensory polyneuropathy is frequent in subjects infected by HIV and especially in AIDS patients. It is usually well-tolerated with mild and even no symptoms and slowly degenerative. TUESDAY, JUNE 2 Prevention/Public Health—Reaching the General Public T_6_1 Market Research for Australia's National AIDS Education Program ALEX PROUDFOOT, E. HAZELL. N. MITCHELL, Department of Health, Canberra, Australia. The Program's objectives are: (a) to provide factual information to the total population and (b) to motivate individuals to adopt behaviors to reduce viral transmission. To identify areas of need, preparatory market research was undertaken. This included: (a) a 30—minute interview/questionnaire covering 750 men and 750 women aged 16 to 60 from the general population; (b) 30-minute questionnaires administered to 200 children aged 12-15 years; and (c) surveys of gay men and IV drug users involving detailed interviews and questionnaires. Preliminary results for adults showed public awareness that casual transmission is not likely (76%), that condoms can reduce the risk of transmission (93!), and that vaccines are not available (9&1). However only 191 were correct on 7 of 8 knowledge items, condom usage appears to be low and 401 still consider the blood supply unsafe. Only A9! are aware of heterosexual transmission and 361 of needle sharing as transmission routes. Seventy—two per cent disagree that sex should be limited to marriage. The public approved general population (911), childhood (81!) and risk group (80%) educational programs. Barriers to education include lack of perceived imediacy of threat (501) and the belief that one‘s own knowledge about AIDS is adequate. T.6_2 Evaluation of Health Education 15 kg‘tain. LORRAINE SHEER, JOE! QEEEE Dept. of Psychology, St Mary's Hospital London UK In the United Kingdom today the Government has embarked upon Health Education and have utilised National Press, Television advertisements and Household leaflet drops. This study presents data on the evaluations of these steps. Higher and lower risk subjects, comprising consecutive attenders st STD clinics, General Practice clinics and university students were monitored before and after each campaign. It was shown that maximum impact occurs at the first time a medium was used (“1.9% overall noticing advertisements at first down to 24.1%). Quality of content was initially low and improved as attention decreased. Priorrto the press campaigns knowledge was limited and errors and anxiety were high. The press campaign increased levels of infor- mation (t=2.13 df 516 p=.03 (first campaign) t=3.97 df=h17 p=.001 (second). Closer analysis showed that this was accounted for by filling in gaps and not adjusting misconceptions. The campaigns had no effect on changing sexual behaviour. Television advertisements had minimal information and used fear arousal to draw attention to leaflets. Exposure was high (95% of subjects monitored had seen the advertisement). General and health education value were low. Subjects found the household leaflet useful. Subjects still state the medical profession as their desired primary source for information. What the Public wants to Know: The National AIDS Hotline T.6.3 n1_c_H_A_£_L_._I. Roseggml‘z. R. KOHHESCHER3. n. communal. R. LAZARovIczl. American Social Health Association. Palo Alto. CA.2Family Health International. Research Triangle Park. NC. 3Centers for Disease Control' Atlanta, GA. In mid—December 1966. operation of the national hotline for AIDS information was transferred from the Centers for Disease Control to the American Social Health Association. The hotline provides a taped message which refers callers to an operator for further information. The new service was expanded from 5 days/week, 9 hours/day to 7 days/week. 24 hours/day coverage. In the first month of operation, the number of calls steadily increased. with taped messages going from 600/day to 1.700/day at its peak and operator calls from lOO/day to 700/day. Twenty-six percent of the operator-answered calls were received on weekends or holidays; 30% were received between the hours of 6 pm and 8 am. Based on a sample of every fifth operator call, most were to request information (69%). with highest demand for information on means of transmission (33%). general information (27%). or testing (15:). The average call lasted 6.8 minutes. Host calls were made because the caller was curious (51!). though a high proportion requested information because they had either symptoms of AIDS. had been tested positive. or had a test pending (23.7%). Most callers were male (52%); 12% of men and 1% of women callers identified themselves as gay. Information was requested by 16% of callers. with twice as many requests coming from women as from men. and the highest proportion of mailings was to the northeast (30%). 56 T.6-4 MEWOFAWAIISMEDIAMAIQIWAGEN‘BRAL POPULAEICN : ANTIBODY TEST REQUESTS AND REASONS. HELBDD NICHOLAS, PAULINE LEONARD, LESLEY GLCNER, DORIS FARR AND DAVID MILLER, Academic Department and Department of Genito Urinary Medicine, Middlesex Hospital/Medical School, london. The impact of a Govermnent television, newspaper and billboard AXIS advertising campaign was assessed by comparing the numbers of requests for antibody testing in the three months before and after the empaign began. Numbers were ocupared in five groups : hanosexual and heterosexual men, bisexual men, heterosexual women and bisexual wanen. Reasons given for requesting the test were also carpeted. In the three months after the campaign, the nunbers overall increased by 239%. Across groups, the numbers were as follads: Han. Men Bet. Men Bi. Men Het. wmen Bi. Wanen N Pre: 58.7% 20.2% 8.4% 12.1% 0.33 431 Post: 27.8’k 37.4% 7.7% 26.8% 0.3% 1032 While the actual number of hamsexual men and bisexual when requesting the test remained constant, the nunbers of heterosexual men and women wanting the test increased four and five-fold respectively. The number of bisexual men doubled. In lower-risk groups, requests for testing concerned anxiety over casual sexual contacts at hone and abroad. No—one from these groups was found HIV antibody positive, and 8% (n=16) were found seropositive Eran hcmosexual and bisexual male attenders. The Govermnenc campaign appears to have raised considerable anxieties in the lowest—risk groups while having little impact in groups with known higher seroprevalence T.6.5 RALPH J DICIEWFNI‘E“, (‘A PI$“. EJ S'IDILER", J HASKIN*“, GE OLIVA", CW RUnfiflHXlIF"*, 'University of California, San Francisco, I““‘San Francisco Ibpartnont of Public Health, and **‘San Francisco Unified School District, San Francisco, CA To design and develop effective AIDS prevention curricula for middle school and high school students in San Francisco, we conducted a baseline survey, teacher trainings, and evaluation of a pilot demonstration progrmn. The base— line survey showed insufficient knowledge of HIV prevention and misconceptions about casual contagion. we subsequently developed AIDS curricula and piloted than in 3 middle schools and 3 high schools. Non-intervention control classes were surveyed at each of the middle and high schools. All 640 students can- pleted a pretest. The intervention group received 3 periods of AIDS instruct- ion. A post-test, identical to the pretest, was administered to both groups. Protests showed that both had conparable knowledge. Post-tests indicated that students in the intervention group had a significantly higher neon score for AIDS knowledge (p<0.0001) than the control group. Specifically, 88% of the students in the intervention group were aware that condone are one way of pre— venting AIDS conpared to 71% in the control group (p<0.0001), and 90% in the intervention group agreed that is is unsafe to have sex with saneone whose health history is unknown compared to 81% of the control group (p<0.0001). We conclude that specially designed AIDS curricula can significantly increase adolescents' short—term knowledge which any result in changes to lower-risk sexual behavior. Evaluation of School-Based AIDS Education CurriculainSanFrancisco T_6'6 AIDS and Adolescents: Knowledge, Beliefs, Attitudes and Behaviors Lee Strunin, R. Hingson, Boston University School of Public Health. Boston, MA. Adolescents are a group at high risk for exposure to AIDS. A random sample survey of 860 16-19 year olds in Massachusetts indicates that many adolescents are still misinformed or confused about AIDS and AIDS transmission. Fifty—five per cent of the adolescent respondents said they are sexually active but only 15 per cent of than reported changing their sexual behavior because of concern about contracting AIDS, and only 20 per cent of those who changed their behavior used effective methods. Eight per cent of both sexually active and inactive adolescents did not know that AIDS is transmitted by heterosexual sexual intercourse. Thirteen per cent had used psychoactive drugs other than alcohol and marijuana with one per cent injecting drugs. Of those psychoactive drug users 8 per cent did not know that AIDS can be transmitted by injecting drugs. There is no significant difference in knowledge between the sexually active and non-active adolescents concerning sexual behavior and AIDS transmission, or between the drug users and non—users concerning drug use and AIDS transmission. Because their knowledge of the mode of AIDS transmission is limited many adolescents, including those in the highest risk subgroups of sexually active or psychoactive drug users, do not know what sexual and drug precautions are needed to prevent transmission of the virus. School systems and health care providers should systematically educate this population about AIDS to counter the current misinformation and confusion. TUESDAY, JUNE 2 Epidemiology—Surveillance: Incidence, Prevalence and Trends 1'] 1 'Demporal Trends of Prevalence and Incidence of HIV Infection Among ' Civilian Applicants for US Military Service: Analysis of 18 Months of Serological Screening Data. * 'k * ** *ti JCHN F. B , D.S. BURKE , L.I. GARDNER , J. HERBOLD , J. VDSKCVIICH **, R.R. REDFIELD , Walter Reed Army Institute of Research, Washington, D.C. Office the Assistant Secretary of Defense (Health Affairs), Washington, D.C., United States Military Entrance Processing Command, North Chicago, Illinois. Each nonth since October 1985, approximately 50,000 civilian applicants for 0.5. military service have been screened for antibody to HIV. of the 641,917 applicants screened during the program's first 12 months 86% were male, 74% were white (not hispanic), and 57% were younger than 21 years. Applicants represented all 50 states, the District of Columbia, and several U.S. territories. overall (1.5/1000), sex—specific (male: 1.6/1000, female: 0.6/1000), and age-specific prevalences did not significantly vary between the first six-months of screening and the second. A "temporal trend term" (first six month period vs. second six—nonth period) did not predict antibody status in a multivariate nodel that controlled for birth year, race/ethnicity, sex, population density, and regional AIDS incidence. when data from high antibody prevalence sub—groups were analyzed separately, there were suggestions of an independent effect of a "temporal trend term." For example, among black male applicants, the adjusted odds ratio (second six months vs. first six months) was 1.07 (95% CI: 0.97—1.18). Estimates of prevalences, incidences, and temporal trends. overall and in demographically and geographically defined sub—groups, from 18 nonths of screening data will be presented. TJ'Z Analysis of Demographic and Epidemiologic Data Concerning HIV Antibody Positive Recruits and Active Duty Air Force Members. RICHARD E. VINN R.A. ZAJAC, M.E. APPLEMAN, G.P. MELCHER, R.N. BOSWELL, M.E. EVANS. Vilford Hall USAF Medical Center, Lackland APE, T . Since the beginning of testing for HIV antibody by the 0.5. Air Force, over 268 active duty members (ADM) and 38 recruits (REC) have‘been identified as being positive using both an Elisa and Western Blot techniques. The majority of both groups are asymptomatic; AIDS has been diagnosed in 14.9\ of ADM. The overall incidence of seropositivity has remained relatively constant at approximately 0.l\ (one per thousand) for REC and ADM. REC and ADM have all been interviewed for demographic variables and examined by the infectious disease service. The average age for REC was 21.8 and for ADM 26.9. The percentage of males was 97‘ REC/96A ADM. A racial difference was observed between REC and ADM with proportionately more black than white REC positive for HIV. Referral locations were diverse and reflected US Air Force assignments in general. Only 19\ REC/11.5\ ADM admitted to homosexual or bisexual activity. The mean number of heterosexual partners of REC/ADM was II.B/68.4 with a range from 1 to > 1000 lifetime partners. Homosexual partners were more frequent: mean > 200. Marriage was infrequent, as predicted, in REC. Twenty nine percent of ADM were married. Age at first intercourse was similar in both groups. Among heterosexual REC and ADM, despite lower sexual promiscuity than occurs in homosexual populations, sexually transmitted diseases were frequently reported. REC/ADM gonorrhea occurred in 30/37\, syphilis in ll/ll.5t, herpes simplex 3/6t. “CH and Condyloma acuminata were reported more frequently in ADM, 17.3\ and 13.5% respectively. Exposures to prostitutes ranged global! from Europe to Southeast Asia and was highly reported in ADM, 37\. Although heterosexual preference in sexual activity and exposure to prostitutes suggests a higher transmission rate by heterosexual sex in the Air Force, disproportionate prevalence of anal condyloma in ADM not admitting to association with high risk groups suggests non-truthful reporting of sexual preference by some ADM and REC. T.7_3 AIDS in Heterosexual Contacts: 3 Small but Increasing Group of Cases MARY CHAMBERLAND, C. WHITE, A. LIFSON, T.J. DONDERO, AIDS Program, Centers for Disease Control, Atlanta, GA. Patients with AIDS who have no identified risk other than heterosexual contact represent 4% of all AIDS patients reported in the United States. As of January 16, 1987, this group includes 521 patients who had heterosexual contact with a person with AIDS or at risk for AIDS (HC) and 589 persons who were born in foreign countries where heterosexual transmission plays a major role. The racial/ethnic distribution of the 521 HC patients is similar to that associated with IV drug abuse: ABZ black, 262 Hispanic, 251 white, and 12 Asian. Males account for only 18% of HC cases versus 782 of non-HC patients who are heterosexual in orientation. The proportion of male HC patients has not increased significantly since 1983. The geographic distribution of HC patients differs significantly by sex: 67% of females are reported from New York, New Jersey, and Florida, compared with 432 of males (p<0.0001). The "at-risk" sexual partners of the HC patients include IV drug abusers (64%), bisexual males (female HC patients only) (14%), individuals from countries wherevheterosexuaI transmission plays a major role (4%), transfusion recipients (1%), and hemophillacs (1%). Risk status of the contact partner is under investigation for the remaining 161. During 1986, the total number of reported HG patients increased by 135% from 218 to 513, while reported cases among homosexual/bisexual men and IV drug abusers increased by 822 and 81% respectively. This reflects a 10 month doubling time for HC cases compared with a doubling in 1b months for homosexual/bisexual men and IV drug abusers. HC patients have increased from 1.0% of all AIDS cases in 1983 to 2.3% in 1986 (p(0.0001). Although the overall proportion of HC cases remains small, it will increase. Additional studies are needed to characterize and track this group. 57 T_7.4 Incidence of HIV Infection in Homosexual Men in a High Risk Area: Implications for Vaccine Trial Design. Cladd E. Stevens, Patricia E. Taylor, Edith A. long, Santiago Rodriguez de Cordoba and Pablo Rubinstein, The New York Blood Center, New York, New York, U.S.A. Early in 1984 the Laboratories of Epidemiology and Immunogenetics of The New York Blood Center enrolled a cohort of 850 homosexually active men in a prospective study of the acquired immune deficiency syndrome. 0f the 773 men tested for anti-HIV by ELISA (Dupont) and Western Blot (Biotech) at entry, 57.7% were seronegative and therefore were considered susceptible to HIV. In the three years since the study began, the participants returned for follow-up every 4 months. As risk factors related to HIV infection became known, the men were periodically advised regarding unsafe sexual practices. As a consequence, sexual activity changed dramatically, especially in numbers of partners and frequency of receptive rectal intercourse. However, in these past 3 years 37 men have seroconverted, a life—table attack rate of 10.0%. The 4-month incidence decreased from 2.25% in the first 4 months to 0.68% by the fourth interval at 1-1/2 years. Since then, however, the incidence has remained stable at about 1% in each 4-month interval. Seroconversion highly correlated, but not exclusively, with the practice of receptive rectal inter- course and nearly 35% of seronegative men continued this practice despite advice to the contrary. These data suggest that, despite educational efforts regarding safer sex, some homosexual men persistently engage in high risk sex. Such men may be candidates for vaccine efficacy trials if vaccines become available for testing. Additionally. the appearance of multiple antibodies to HIV proteins and T-lymphocyte alterations at the time of seroconversion sug- gest end-points which may distinguish between vaccine and virus-induced anti- body and end-points for evaluation of vaccine efficacy. T_7.5 The Surveillance of Clinical Viral Hepatitis Type B and Primary, Secondary and Early Latent Syphilis in Homosexual and Bisexual Men in MN: Implications for Human Immunodeficiency Virus (HIV) Transmission MICHAEL T. OSTERHOLM, K.L. MACDONALD, S.J. SCHLETTY, M.D. NIELSEN, R.N. DANILA, Minnesota Dept. of Health, Minneapolis, MN, USA. Since 1982, a marked decline in the incidence of rectal gonorrhea and syphilis has been noted among homosexual men nationwide. To determine the implications of declining rates of selected bacterial sexually transmitted diseases (BSTD's) on HIV transmission among homosexual and bisexual men, we compared statewide surveillance data for these groups obtained between January 1982 and July 1986 for incident cases of primary, secondary and early latent syphilis and acute clinical viral hepatitis type B (with hepatitis B serving as a marker for the sexual transmission of HIV). A mean of 79 cases (range, 61 to 90) of syphilis occurred during each six-month interval before July 1984. Despite similar surveillance efforts, marked decrease in incident cases was noted between July 1984 and June 1986. with a mean of 16 cases (range, 11 to 21) reported for each six-month interval However, no change was noted in the number of acute clinical hepatitis B cases reported through active laboratory-based surveillance. The number of clinical hepatitis B cases reported by six-month interval ranged from 12 (July-December 1983) to 19 (January-June 1986); intravenous drug abuse could be documented as a risk factor for only 8% of cases. Results of this study indicate that among homosexual and bisexual men declining rates of syphilis and other BSTD's among homosexual and bisexual men may not reflect a concurrent reduction in the transmission of selected viral STD‘s, such as viral hepatitis type B. We believe these results may have significant implications when interpreting the impact of risk reduction programs on HIV transmission nationally. T 7.6 Community Surveillance for HIV Infection in Zaire Robert W. RYDER*, W. BERTRAND**, R.L.COLEBUNDERS*, B. KAPITA*, H. FRANCIS*, M. LUBAKI*, *Projet SIDA, Kinshasa, Zaire, **School of Public Health, Kinshasa. To assist Zairian physicians in diagnosing HIV infection, a no—cost screening program was established at Mama Yemo Hospital, Kinshasa. Despite logistic difficulties in transport, sera from 8871 patients were referred during 1986, of which 54% was HIV(+) by repeat ELISA. Among children 70% of cases occurred between the age of 0—3. Three times as many children aged less than 1 year were HIV(+) compared to children aged 1—3 years old. Seventy percent of all cases occurred in patients aged 15—40 years. Striking differences in the female: male sex ratio were observed: less than 15 years old F:M ratio=1:1; 15-30 years F:M ratio=6:l; greater than 30 years F:M ratio=.64:l. The diagnostic accuracy(number of tests positive/total tests submitted) of physicians working in the Tuberculosis Sanitarium or in adult diarrheal disease wards were the highest; 85% and 74%, respectively. These data docu- ment in Zairian physicians a considerable awareness of and ability to clini- cally diagnose HIV infection. The overall femalezmale infection ratio in our study(1.1:l) is similar to the figure widely used in describing the epidemiology of HIV infection in Africa. However, we found that cases of infection clustered in two risk groups, young women(age 13 to 25) and middle to older aged men. These differences in age-specific, sex—specific HIV infection rates should be considered before any HIV prevention activities involving behaviorial modifi- cation in Africa are initiated. TUESDAY, JUNE 2 Clinical Trials—AZT and Ribavirin T_8.1 Decline in Serum HIV p24 Antigen (Ag) Treated with AZT. RICHARD E CHAISSON, J—P ALLAIN, M LEUTHER, W PARKS; in Patients S LEHRMAN. P VOLBERDING, UCSF School of Medicine, Abbott Laboratories, Burroughs-Wellcome 00., USA. To assess the anti—retroviral effect of AZT in vivo, we measured serum HIV-Ag in 157 AIDS or ARC patients enrolled in a multicenter placebo-controlled trial. Patients received AZT 250 mg or placebo every 4 hrs, with dose reduction for toxicity. HIV p24 Ag was detected using a polyclonal IgG sandwich enzyme immunoassay. Sera were obtained at entry and at 4 week intervals. 36 of 79 (46%) AZT patients and 40 of 78 (51%) of placebo patients had Ag detected during the trial. 28 patients in each group had a baseline and later specimen for comparison. Baseline HIV—Ag levels were 297 pg/ml for AZT patients and 234 pg/ml for placebo patients (p=NS). Significant decreases in HIV-Ag in AZT patients were seen at 4 weeks (AZT group mean = 70 pg/ml, placebo mean = 223; p=0.0002), 8 weeks (AZT mean = 56 pg/ml, placebo mean =233, p< 0.0001) and 12 weeks (AZT mean = 53 pg/ml, placebo mean 84 pg/ml: p=0.0052). Differences persisted through 20 weeks, though sample sizes were small. No HIV—Ag positive subject in either group had anti—p24 antibodies, and decline in HIV-Ag in AZT patients was not associated with reappearance of anti-p24. We conclude that HIV— Ag levels are an important marker of anti-retroviral activity in a substantial proportion of AIDS and ARC patients. T.8.2 Therapy of AIDS Patients with Early Kaposi's Sarcoma with 3'-Azido-3'Deoxythymidine ROBERT WALKER, H.C. LANE, H. MASUR, J. KOVACS, S. CARLETON, A.S. FAUCI, et al., National Institutes of Health, Bethesda, MD. 3'-Azido—3'-deoxythymidine (AZT) is a nucleoside analogue which has been shown capable of inhibiting the replication of HIV in vitro and prolonging life in AIDS patients 120 days following an initial—Bout of Pneumoc stis carinii pneumonia. The present study was designed to determine t e e ects of All on a group of patients at an earlier stage of HIV infection, namely AIDS patients gith Kaposi's sarcoma only and with more than 200 T4 lymphocytes/nun. A 40 patient study was designed with patients randomized to 1 of 4 groups. Group 1 patients received placebo, group 2 patients received 250 mg AZT po q4h, group 3 patients received 0.05 mg/kg AZT iv q4h, and group 4 patients received 2.5 mg/kg AZT iv q4h. Patients were treated for 12 weeks. As of this writing, 36 patients have entered the study and 22 have completed 12 weeks. Analysis of the available data has revealed that there was a reduction in Kaposi's sarcoma in 0/6 patients on placebo and 4/16 patients on drug. Viral cultures have become negative in 1/6 patients on placebo and 6/15 patients on drug. No significant changes have been seen in innmnologic parameters including total lymphocyte and subset counts, lymphocyte blast transformation to mitogens or antigens or natural cytotoxicity. Thus, based upon reduction in KS lesions and decline in viral shedding, AZT may be of value for the treatment of early AIDS patients with Kaposi's sarcoma. T 8_3 Clinical Evaluation of the Central Nervous System in HIV Infected Patients on Azidothymidine (AZT). C.J. KENNEDY, R.S. TESCHKE, J. HESSELINK, J. BERGER, M. FISCHEL, D. RICHMAN, et al, University of California, San Diego, CA. During a double-blind, placebo—controlled trial of AZT, 32 AIDS and ARC patients in San Diego were intensively investigated to detect any effect of AZT on the central nervous system. In addition to the standard protocol, study participants had: peri— pheral blood and CSF culture to detect HIV; magnetic resonance imaging (MRI) of the brain; a detailed clinical neurological examination; and a comprehensive neuropsychiatric assessment. There was no effect of AZT on the frequency of positive HIV culture in blood or CSF, nor on the patterns of MRI abnormality. The clinical neurological examinations showed a beneficial effect of AZT; 0/13 patients improved in the placebo group, and 5/16 in the treated group. However, the ovegall effect did not meet criteria for statistical significance (P = 0.12, Mantel-Haenzel Test). Neuropsychiatric testing detected no difference between the groups. These studies have been extended in two ways. First, CSF specimens are under analysis to determine HIV antigen load, using an antigen capture assay. Second, the clinical neuro- logical examination data is being pooled with comparable data in a further 30 patients from another AZT study center (Miami) to evaluate better the significance of the differences described here. Our working hypotheses are: (1) that AZT leads to an improvement in neurological functioning, and (2) that physical neurological examination is the most sensitive available tech- nique to detect this effect. 58 T_8.4 THE TOXICITV OF 3'—AZIDO-3'—DEOXVTHVM1DINE (AZIDDTHVMI— DINE) IN THE TREATMENT OF PATIENTS HITH AIDS AND AIDS— RELATED COMPLEX: A DOUBLE—BLIND, PLACEBO—CDNTROLLED TRIAL. AZT COLLABORATIVE HDRKING GROUP A double-blind, placebo-controlled trial of oral azidothymi— dine (AZT) was conducted in 282 patients with AIDS or AIDS- related complex (ARC). Although significant clinical benefit was documented serious adverse reactions, particularly bone marrow suppression, were also observed. Nausea, myalgia, insomnia and more severe headaches were reported more frequently by AZT recipients. Macrocytosis developed within weeks in most subjects. Anemia, with reductions of >ES% in baseline hemo— globin levels. occurred in 38% of AZT recipients and 13% of placebo recipients (p (0.05). Hemoglobin levels bolow 7.5 g/dl developed in 24% of AZT recipients and 4% of placebo recipients (p <.001). 21% of AZT recipients and only 4% of placebo recip- ients required multipls transfusions (p (.001). Neutropenia of less than 500 cells/mm occurred in 16% of AZT recipients compared to 2% of placebo recipients (p (.001). Patients who entered the study with low T“ lymphocyte counts, low serum vitamin B12 levels, low hemoglobin. or low neutrophil counts were more likely to experience hematologic toxicity. Acetaminophen co—administration was also associated with a higher frequency of hematologic toxicity. Although a subset of patients has tolerated AZT for an extended period with few problems, the drug should be administered with caution because of its recognized toxicities and the limited experience acquired with the drug to date. T85 “huunuhnpmuuumofmehwmumfiwcnuueflu) ' ' to the acquired immune deficiency syndrome (AIDS). P.U.A. HANSELL*, P.N.R. HESELTINE**, 3.3. ROBERTS***, G.H. DICKINSON****, J.H. LEEDOH** et a1., *University of Texas, Houston, TX, **Univeraity of Southern California, Loe Angeles, CA, ***Cornell University, NY, ****University of Miami, FL, 0.5.11. Ribnvirin, a synthetic gunnosine nucleoeide analogue has 15 vitro activity against the human immunodeficiency virus (HIV). Ribovirin’a role in preventing progression of LAS to AIDS was evaluated in a randomized, double-blind, placebo-controlled, multicenter trial. One hundred and sixty—three homosexual men with LAS were treated with oral ribavirin or placebo for 24 weeks, followed by no treatment for four weeks. All were HIV culture positive. hnd lymphndenopathy for six months or more, hematocrits Z 351 and fewer than 500 (1 5.0. of the method) TA+ cells. Those with chronic oymptoml of HIV infection (diarrhea, fever, thrush, weight loss) were excluded. Fifty-two received 800 mg of ribovirin daily and none developed AIDS; 6/55 (111) given 600 mg/doy of ribnvirin and 10/56 (18!) taking placebo developed AIDS (p-0.007). Difference in outcome correlated with ribnvirin plasma levels. This therapeutic effect was not explained by differences in Tb+ cells or hematocrit at initiation of therapy. Qualitative HIV cultureo remained positive and measured immunologic function did not increase in the treated groups. Three of 107 (2.81) receiving ribavirin discontinued treatment because of insomnia or nausea/vomiting. Ribnvirin was associated with a mild compensated one-in; no one required a blood transfusion. There was one death, AIDS-related, in the placebo group. Prolonged ribavirin therapy is well tolerated and delays the progression to AIDS of immunologically compromised men with LAS. Ribovirim deserves further study as a therapeutic agent for HIV infection. T 8 6 Serum HIV Core Antigen in Symptomatic ARC Patients Taking Oral Ribo- ' ' virin or Placebo. ANDREW VERNON? R.S.Schulof?*for the RIBAVIRIN ARC STUDY GROUP. *Johns Hopkins University, Baltimore MD.**George Washington University, Washington DC‘ We measured HIV p24 core antigen (AG) in serial sera of symptomatic ARC pat- ients as part of a multicenter, placebo-controlled, randomized trial of oral Ribavirin. Fifty-six men with ARC were randomized to placebo or one of two oral ribavirin regimens. AG was measured by sandwich enzyme immunoassay in samples taken at weeks 0 and 12. Counts of T4 lymphocytes and culture for HIV were performed at both times. Mean AG levels (+/— S.E.) were: Week 3 Placebo 600 mg gd 800 mg gd 0 56 275 +/— 81 325 +/- 118 174 +/-51 12 49 203 +/- 60 382 +/~ 114 324 +/- 85 Our data fail to show a statistically significant difference in mean AG levels of ribavirin-treated ARC patients and placebo controls (p=0.28 by ANOVA; p-O.19 by t test comparing drug and placebo). There was no significant difference in change in mean T4 cell counts when comparing patients on drug with those on placebo (p=0.35, t test). Culture positivity was similar in drug and placebo groups at week 0 (29/37 drug; 14/19 placebo) but was different at week 12 (23/33 drug; 15/16 placebo; p80.08 FET). Five patients developed AIDS by Week 12. Seventeen of 49 men tested on two occasions had no AG at either time. These data are qualified by small numbers and by 7 drop-outs. We will present data on 150—200 patients, measured at 5 points over 24 weeks, with quantitative aspects of culture. In sum, we found no effect of oral ribavirin on serum AG levels; our data suggest that an effect on virus culture positivity may be present. TUESDAY, JUNE 2 I C I Immunology—HIV-Speufic Cytotoxnclty T 9 1 HIV eng- and gag- Specific Cytotoxic T Lymphocytes (CTL's) in ' ' Seropositive Subjects wig S. CHAKRABARTI**, B. MOSS**, T. J. PARADIS*, M. S. HIRSCH*, R. T. SCHOOLEY*. * Massachusetts General Hospital and Harvard Medical School, Boston, MA 0211a. **I.aboratory of Viral Diseases, NIAID, NIH, Bethesda, MD 20892. Using recombinant vaccinia viruses to express HIV genes, we have detected circulating HIV-specific CTL's in homosexual males seropositive for the AIDS agent. EBV immortalized B cell lines established from 8 seropositive subjects and 5 seronegative controls were infected with recombinant vaccinia viruses expressing the HIV m (VAC/env) or gag (VAC/gag) gene, or a control vaccinia vector expressing the bacterial lac 2 gene (VAC/lac), and used as targets in a chromium release assay. Freshly isolated autologous peripheral blood mononuclear cells were used as effector cells. HIV m- and ggg- specific cytotoxic responses were detected in seropositive subjects, but not seronegative controls. At an effector: target ratio of 100:1, mean specific lysis of the different vaccinia-infected target cells in seropositive subjects was a) VAC/env 37.5 ‘1 6.2% (p<.005 vs VAC/lac) b) VAC/gag 17.2% i 3.8% (p<.05 vs VAC/lac) c) VAC/lac 11.2 1 3.3%. For seronegative subjects. these values were a) VAC/env 8.6 g 1.2% b) VAC/gag 7.8 i 1.1t c) VAC/lac 7.7 1 1.1%. The ep_ - specific cytotoxic response was inhibited by 67‘1008 by addition of a CD3-specific monoclonal antibody, indicating that the effector cells are T lymphocytes. This demonstration of HIV-specific cytotoxicity in seropositive individuals should prove useful in further investigating the immunopathogenesis of AIDS and in evaluating vaccine strategies. T9 2 Detection of HLA Restricted Human Immunodeficiency Virus (HIV) ' Envelope Antigen-Specific Cytotoxic Lymphocytes (CTL). DAVID H. SHEPP,* D. W.***. S. CHAKBABARTI,** D. MOSS,**, P. DAGUILLARD,**** AID G.V. QUINNAH,‘ *Division of Virology, FDA, **HIAID. IIIH, ***HCI. IIIH, Bethesda, MD and ****o.c. Comm. Public Health, Hashington, DC, USA Because cell—associated virus may be important in transmission and pathogenesis of HIV infection. vaccine-induced protective inmmnity may require induction of CTL killing of infected cells. To measure HIV envelope—specific CTL. peripheral blood mononuclear cells from asymptomatic HIV seropositive individuals were stimulated i_n vitro for 5 days with autologous, irradiated, HIV infected T-lymphoblasts. Human skin fibroblast target cells matched to the donor at one or more HLA—A or B loci. or mismatched, were infected with recombinant vaccinia containing the Whole envelope gene of the H'l‘LV-IIIB strain of HIV. The same target cells infected with recombinant vaccinia lacking this insert served as controls. Targets were labelled with 51Cr and at 19 hours after infection were incubated with effector cells at an effectorztarget ratio of 25—30:1 for 4 hrs. 5l-Cr release was then measured and the percent lysis calculated. HIV envelope-specific lysis was determined by subtracting the results with the control from those with the envelope recombinant. six of 8 donors tested showed significant (p<0.05) HIV envelope-specific lysis (mean 1. lysis 9.4 +/— 2.2). Cells from HIV seronegative donors did not show significant lysis. Among donors showing positive responses, 8 of 12 matched but only 2 of 9 mismatched targets were lysed (p=0.05). Memory cells capable of developing HLA—restricted, HIV envelope-specific cytotoxic activity are present in the peripheral blood of some asymptomatic, HIV infected individuals. HIV envelope antigens can serve as targets for these responses and measurement of CTL may be an important part of evaluation of the immunogenicity of candidate vaccines. T'9_3 Cytotoxic T Cells Directed Against Target Cells Expressing HIV-1 Proteins SCOTT KOENIG, P. EARL, D. POWELL, H.C. LANE. B. MOSS, A.S. FAUCI, et al., NIH, NIIID, Bethesda, MD. We previously detected HIV-specific cytotoxic T cells (CTL) in peripheral blood mononuclear cells (PBMC) of healthy HIV seropositive individuals as well as 2 AIDS patients who had received bone marrow (BM) transplants from their HIV seronegative identical twins. HIV-specific CTL activity was not found in PBMC of HIV seronegative individuals or in non-transplanted AIDS patients (2nd Intl Conf AIDS). In order to determine which viral proteins are important in the detection of HIV-specific CTL responses, recombinant vaccinia viruses expressing different products of the HIV genome were utilized. FHA-stimulated PBMC or EBV-transformed B cells were infected with recombinant vaccinia viruses expressing either gp120 ggd 41 (env), gplZO alone (env), or gp55 (gag) and used as targets in a 4 hour Cr-release cytotoxicity assay. Cells infec- ted with a vaccinia vector that contained a bacterial lac gene were used as a control. PBMC obtained from healthy HIV seropositive individuals or a cohort of 12 AIDS patients participating in a study of AZT used in combination with BM transplantation, served as effector cells. Most CTL activity was detected against the env region (15-48% specific lysis at an effector2target ratio of 100:1) although lysis of target cells expressing gp55 was also seen. HIV was sporadically isolated from PBMC of most of the individuals with CTL activity. Given the fact that in vitro priming was unnecessary to elicit CTL responses, these data suggest that HIV specific CTL are stimulated in vivo and may be effective in suppressing viral replication. These studies have potentially important implications in the delineation of the nature of a protective immune response in HIV infection and in devising strategies for vaccine development. 59 119.4 GplZO-Specific Cell-Mediated Cytotoxicity in Patients Exposed to HIV KENT J. WINHOLD“, H. KIM LYERLY", T.J. MATTHEWS*, M.R. CAIRNS**, D.T. DURACK”, AND D.l’. BOLOGNESI*, *Department of Surgery and “Medicine, Duke University Medical Center, Durham, NC As part of an ongoing investigation of cellular anti-HIV reactivities, we examined the ability of peripheral blood mononuclear cells (PRMC) obtained from patients at various stages of disease to directly lyse cells bearing only gplZO determinants. Autoiogous CD!» gills were coated with purified HTLV-III gp120 and used as targets in 4-hour Cr release assays for cell—mediated cygotoxicity (CMC). CplZO—specific CMC was apparent in HIV seropositive individuals at all stages of disease. Levels of CMC were highest in asymptomatic patients while ARC and AIDS patients exhibited only sporadiE and law (MC. The activity was not MIC—restricted and was mediated by a CD3 , CD4 , CD8 , CD16 population of effector cells. Although not strictly Interleukin 2 (IL—2)-dependent, CMC was greatly augmented by exogenous IL-2. Cold target competition studies revealed that anti-gp120 effector cells also recognized K562 targets. Taken together, these results suggest that a sub—population of 'NK—like' effector cells, not present in eeronegative individuals, mediates the destruction of gp120 coated targets. The antigen receptor on these cells recognizes 'group' determinants, since CM targets coated with purified gp120 from the widely divergent HTLV—II isolate were lysed to the same degree as cells coated with HTLV-III gpl . These resul s not only document the presence of virus-specific cellular cytolytic elements present in HIV seropositive individuals but also highlight gpIZO as a target antigen for immune cytolysie. Additionally, the ability of gp120 adsorbed CD4 cells to serve as targets for CMC suggests a possible mechanism of immunopathogenesis in which lympholysis might occur in the absence of infectious virus spread. T9 5 Cytotoxic T Cells, that Recognize Human Immunodeficiency Virus ' ' (HIV) Envelope Glycoproteins, Isolated from chimpanzees Immunized with a Recombinant Vaccinia Virus Expressing HIV Glycoproteins JOYCE H. ZARLING“, PATRICIA A. HORAN*, JAN HcCLURE+, PEN'NATHUR SRIDHAR*, JORG . C G *, and SHIU-wK HUN *Oncogen, Seattle, VA; i”rSouthwest Foundation for Biomedical Research, San Antonio, TX; +Genetic Systems Co p., Seattle, VA. Little is known concerning ’1‘ cell mediated immunity to V. However, we previously reported that a recombinant vaccinia virus, v-env5, expressing HIV envelope (env) glycoproteins 3PM and gpllO induces T helper cells in macaques, that recognize HIV by proliferating and by producing interleukin-2. It was not determined, however, whether immunization with such a recombinant virus can also prime HIV specific cytotoxic T cells (GIL). In this study, immunization of chimpanzees, the closest relative of man, with v-env5 (but not with a recombinant vaccinia virus that expresses a herpes simplex virus glycoprotein) resulted in the generation of T helper cells that proliferate following stimulation with HIV or with purified env glycoproteins. In addition, cytotoxic T cell clones were also isolated from v—envS immunized chimpanzees following stimulation of lymphocytes with env glycoproteins. These CTL clones lyse autologous target cells infected with v-envS but not with parental vaccinia virus. Our results thus indicate that immunization of chimpanzees with a recombinant vaccinia virus expressing HIV envelope glycoproteins results in the generation of HIV specific T helper cells and CH. and also that HIV envelope glycoproteins serve as target antigens for cytotoxic T cells of primates. HIV specific T helper cells and CTL. such as those we have demonstrated, may play a role in limiting dissemination of HIV or preventing the development of AIDS. 119.6 HIV Antibodies in Human Sera Induce Cell-mediated Lysis of HIV— Infected Cells. EMMANUEL A. OJO-AMAIZE, P.G. Nishanian, D. Keith, Jt., J.L. Fahey and J.V. Giorgi. UCLA School of Medicine, Los Angeles, California, U.S.A. The capacity of human imzmmodeficiency virus (HIV) antibody-positive sera to recruit non-immune lymphocytes to lyse HIV-infected T cell lines was investi— gated. Sera from twenty-seven asymptomatic homosexual men with normal CD4/CDB cell ratios were shown by ELISA to have antibodies to the whole HIV. At dilutions between 10'2 and 10-5, twenty-two of these sera caused lysis of HIV- infected target cells (HOLT—4f and CEM-CCRF) above the level of spontaneous lysis caused by either peripheral blood lymphocytes (PBL) alone, or lysis of HIV-antibody—coated uninfected target cells in the presence of added PBL. HIV- antibody negative sera did not cause lysis. Fractionation of the HIV-antibody positive sera on protein-A affinity columns showed that the ADCC—inducinq molecule resided in the Ig-fraction. Thus, identification of the extra cytotoxic activity in the IgG fraction is indicative of antibody-dependent cellular cytotoxicity (ADCC) . Varying capacity to cause ADCC was observed among the different HIV-antibody positive sera. Using radioimmunoprecipitation- SDS-PAGE analysis with [35$]-methionine-labeled HIV-infected cells, it was shown that antibody to the HIV envelope protein, gplzo was present in reactive, but not in ADCC inactive, sera. There was no correlation, however, with presence or absence of antibodies to p24, p55 or gp41 antigens. These results suggest that HIV envelope proteins play an important role in HIV-specific responses. TUESDAY, JUNE 2 Psychosocial—Psychosocial Research: At Risk Populations vention of AIDS: An urgent research agenda. T.1ll.1 Th° Pm“? . . . . Susan Allen, Mindy Fulhlove, Thomas Coates. University of Caiifomia, San Francisco, CA, 94143. AIDS is a fatal and incurable disease that has already had an unprecedented impact on the health and social structure of our society, and the adverse effects of the epidemic will intensify as those who are already infected develop clinical disease. These facts lend urgency to the nwd to develop more effective approaches to preventing the further spread of infection. AIDS is a behaviorally transmitted disease, and culture-specific behavioral interventions are the only known approach to primary prevention. In order to develop a more effective public health response there is a need to greatly enhance our pursuit of the following research agenda: 1. Population based epidemiologic studies to inform us on the distributions of HIV infection, and on the distributions of high risk behaviors and their antecedents, in various segments of the population, and, 2. Health education intervention studies to reveal the most cost—effective approaches to reducing high risk behaviors, and to tailoring preventive strategies to those segments of the population (such as the black and hispanic minorities) that are at disproportionely high risk. This research agenda is staggering in size, since these issues should be addressed in many cultural and language settings throughout the world, not just in the United States. There is a need for more fiscal resources to support these efforts, and for more health scientists to become involved in their pursuit. T 10_2 Persistence and Change in Sexual Behavior and Perceptions of Risk for AIDS among Homosexual Men. KAROLYNN SlEGEL, J.Y. CHEN, F. MESAGNO, G. CHRIST Memorial Sloan—Kettering Cancer Center, New York, NY, USA A longitudinal study of modifications in sexual behavior among asymptomatic homosexual men (n=161) in New York City was conducted. Participants were interviewed at two time points (T1 and T2) six months apart. Based on respon- dents' reports of their behavior during a recent "typical" month, the riski- ness of their sexual behavior was scored from 0 to 4. Scores were based on available epidemiological evidence concerning sexual behaviors associated with HIV associated conditions. Respondents were also asked to rate their own be— havior on a scale from i to 10 based on how risky they thought their current practices were in terms of contributing to their chances of getting AIDS. When change between T1 and T2 was examined, a number of patterns emerged. For almost halt (47%) of the respondents there was no change in their risk rating. About one—third (36%) received a lower risk rating at T2, and the re- maining men (17%) received a high risk rating. A full 41% of the men studied were practicing risky sex at both assessment points, while only 29% were en- gaging only in safe sex at the two time points. The remaining 30% had shifted categories (20% risky at Ti, safe at T2; 10% safe at T1, risky at T2). When respondents' subjective ratings of the riskiness of their behavior were compared with the objective scores, it was determined that as many as four out of every five men engaging in risky sexual behavior may be underestimating the danger inherent in their behavior. The implications of these findings for future public health efforts will be discussed. TI10'3 KNOWLEDGE OF H.I.V. CONTAMINATION MODALITIES AND ITS CONSEQUENSE ON SEROPOSITIVE PATIENTS BEHAVIOUR. A.PESCE, M. NEGRE, J.P. CASSUTO. Ligue Régionale Frangaise de Lutte contre le S.I.D.A. — 8, rue Hatel des Postes — NICE - 06000 — FRANCE We made investigation on behaviour of 150 patients infor— med of their H.I.V. seropositivity, Living on French Riviera, which is the second French place for A.I.D.S. rate. Characteristics of this population are the following : drug addicts : 100 (67 %J, homo and bisexuals : 32 (21%) exclusive heterosexuals : 10 (6,5 %), transfused : 8 (5,5 %) ; median age (17—79) : addicts : 25, homo and bisexuals : 29, transfused : 41. For each group specific contamination risk was known on an average of 16 months for addicts, 35 months for transfused patients. Drug addicts stopped syringe exchange in 51 % of cases, drug (heroin) in 36 % and use condoms : 33 %. Among 73 % of homosexuals who carry on sexual practices, 37 % use condoms. almost of heterosexuals who carry on sexual activity use protective mean (4/5). In this study, transfused population is not significant because of lack of seropositivity knowledge and lack of sexual activity in all patients related to severity of initial disease. Although these results appear disappointing, they do signify a real change in practice of risk patients, which justify repe- titive and specific public information conciousness being heterogenous according to the groups. 60 T 10 4 Preventing Human Immunodeficiency Vlrul Contagion Among I I Intravenoul Drug Users: The Impact of Street-Bleed Education on Risk—Behavior John K. Hatters, Ph.D. Height—Anhbury Free Medical Clinic- An evaluation of n street-based, AIDS prevention and hellch education project directed at out—of-trelement intravenous drug unern (IVDUI) who conducted In San Francisco. Two waves of IVDUI were interviewed and data obtained on drug use and medical hlntory, sexual practicel, needle-hygiene, beliefs and knowledge about AIDS transmission, and HIV serology performed. Each wave contained respondents who were sampled from non-cllnlcnl populations of IVDUs not connected with treatment program] and clinical populations of IVDUs enrolled In 21-day drug-detoxification programs. The first wave (n-ABB) was conducted during winter/Spring, 1986 end the second wave (n-SOO) was conducted during Winter/Spring I987. The intervention-- which placed "community health outreach workers" in San Prnnclneo neighborhoods with lnrgo numberl of IVDUl—-wna Implemented It the approximate mid—point between observations. Preliminary findings suggest significant change between woven in adoption of the recommended needle-hygiene procedural. Additional findings Include reported reductions In needle-shoring, increased use of condoms, and increased AIDS knowledge. HIV infectlvlty was significantly higher among the non—clinical group (161) than the clinical group (71) in the 1986 wove. Preliminary results suggest an approximate doubling of HIV infectlvlty between the 1986 and 1987 woven. T 10.5 Determinants of Current Psychiatric Disorder in AIDS Spectrum Patients. SUSAN TROSS*, D.A. HIRSCH, E. RABKIN, C. BERRY, J.C.B. HOLLAND. Memorial Sloan-Kettering Cancer Center, New York, NY. Current psychiatric status was examined at diagnosis in gay men with AIDS (A=90) and ARC (ARC=40), and compared with that of healthy gay men (H=l49) in New York City. Standard psychiatric interviews, using structured interview schedules, were conducted to obtain D.S.M.—III diagnoses by reliable interviewers (Kappa = N.70). 42% of the entire sample had any current disorder-- chiefly adjustment disorder (81% of disorders). Rates were higher for the A (52%) and ARC (63%) groups than for the H group (31%). The A, and especially, ARC groups also exceeded the H group on self-reported psychological distress at the Brief Symptom Inventory (p=.001). Hierarchical multiple regression analysis was performed to identify the determinants of psychiatric disorder. The resulting equation accounted for 20% of the variance. A series of significant predictors (p£.01) were associated with the following increments in explained variance: history of past major affective or anxiety disorder (3%); diagnosis of AIDS or ARC (5%); number of AIDS spectrum physical symptoms (4%); and extent of self—reported psychological distress (1%). Reactive psychiatric disorders are a common and highly treatable complication of AIDS and ARC-- which may be readily detectable from the patient's SWE report. 1106 Two-Year Longitudinal Study of Behavioral Risk Reduction in a Cohort of Homosexual Men JILL G. JOSEPH*, S. Montgomery*, R.C. Kessler*, D.G. Ostrow*, C.A. Emmons*, JJ’. P'HEH , niversity of Michigan, Ann Arbor, MI, USA, “Northwestern University, Chicago, IL, USA A cohort of approximately 650 homosexual Chicago men provided behavioral and psychosocial data from mid-1984 to mid-1986. A four level objective risk index was constructed and validated using HIV serological data. This index summarizes number and type (e.g. monogamous; anonymous) of sexual partners, frequency of receptive anal intercourse, and use of condoms. Although 35% of the cohort was categorized as at high risk originally, by Wave 4 this was true of only 6.0%. Similarly, while 6.1% were originally completely avoiding risk behaviors, two years later 13.4% were doing so. Components of the health belief model at Wave 1 were used as predictors in a series of multiple logistic regressions which examined subsequent risk reduction. Indices were constructed to quantify knowledge of AIDS, perceived risk, perceived efficacy of behavioral change, social network characteristics, peer norms, difficulties with sexual impulse control, and beliefs in technological solutions to the AIDS crisis. of these, knowledge (p<.01-.05), peer norms (p<.01-.02), and difficulties with sexual impulse control (p<.01-.02) were consistently predictive of behavioral risk reduction. This provides evidence for the role of cognitive, social and psychological factors 'in behavioral risk reduction. TUESDAY, JUNE 2 Roundtable Discussions 1.11 Access Issues Associated with AIDS: Discrimination, Services, Care Panel Moderator: Jeffrey Levi National Gay and Lesbian Task Force Washington, D.C. Tom Stoddard, Lambda Legal Defense and Education Fund, New York, New York Ben Schatz, National Gay Rights Advocates, San Francisco, California Tim Westmoreland, Council House Subcommittee on Health and the Environment, Washington, D.C. Adam Carr, Victorian AIDS Council, Richmond, Australia Katy Taylor, New York City Human Rights Commission, New York, New York T.12 Use of AZT in HIV Infections Panel Organized Byr John La Montagne National Institute of Allergy and Infectious Diseases Bethesda, Maryland Douglas Richman, Veterans Administration Medical Center, San Diego, California Paul Volberding, University of California, San Francisco, San Francisco, California Margaret Fischl, University of Miami, Miami, Florida Sandra Lehrman, Burroughs Wellcome Company, Research Triangle Park, North Carolina T.13 Encouraging Physician Counseling for AIDS Prevention Panel Organized By: Neil R. Schram LA City/County AIDS Task Force Los Angeles, California David McEwan, Honolulu Medical Group. Honolulu, Hawaii Brian Willoughby, Vancouver, Canada Mark Behar, Milwaukee, Wisconsin Alan Novick, Yale University, New Haven, Connecticut 61 T.14 Legal, Ethical and Public Policy Issues: International Perspective Panel Moderator: Richard Riseberg Public Health Service, HHS Washington, D.C. Ronald Robertson, Department of Health and Human Services, Washington, D.C. LeRoy Halters, Joseph and Rose Kennedy Institute of Ethics, Washington, D.C. Bernard Dickens, University of Toronto, Toronto, Canada Harvey V. Fineberg, Harvard University, Boston, Massachusetts Sev Fluss, World Health Organization, Geneva, Switzerland Michael D. Kirby, Court of Appeals, New South Wales, Australia Eric Matthews, University of Aberdeen Kings College, Aberdeen, Scotland Helen Roscam—Abbing, University of Limberg, Maastricht, The Netherlands Brenda Almond, The University of Hull, Hull, England T.15 Psychological Distress and Maintenance of Behavior Change in HIV Illness Panel Organized By: Peter Bridge ADAMHA Bethesda, Maryland Panel Moderator: Ellen Stover National Institute of Mental Health Rockville, Maryland John Newmeyer, CEO Youth Projects, Inc., San Francisco, California Peter M. Davies, South Bank Polytechnic, London, England Jeff Moulton, Langley Port Psychiatric Institute, San Francisco, California David Ostrow, University of Michigan, Ann Arbor, Michigan Thomas Coates, University of California - San Francisco, San Francisco, California Biology of HIV T.16.1 Flossie Won —Staal, National Cancer Institute, National Institutes of Health, Bethesda, Maryland. The AIDS Virus Genomes: Structure and Function. ABSTRACT NOT AVAILABLE AT TIME OF PRINTING TUESDAY, JUNE 2 T 16.2 Molecular Basis for Approaches for Diagnostic, Therapeutic, and Prophylactic Measures for Control of AIDS. WILLIAM A. HASELTINE**, JOSEPH SODROSKI*, CRAIG ROSEN*, ERNEST TERWILLIGER*, ANDREW DAYTON*, ROBERTO PATARCA*. *Dana-Farber Cancer Institute, Dept. of Bio- chemical Pharmacology, Harvard Medical School, and **Harvard School of Public Health, Dept. of Cancer Biology, Boston, MA. The studies of the replication cycle, genetic regulatory pathways and mecha— nisms of cellular cytopathicity of the AIDS virus will be presented in the con- text of their potential for the development of improved techniques for the con- trol of the disease. Specifically, studies of the gig and trans elements of the viral genome will be presented. In this study, the structure/function of envelope glycoprotein will also be discussed as it pertains to early steps of infection, cytopathic effect and immunoprophylactics. The potential for other viral genes as targets for anti-viral drugs, including the protease reverse transcripatase and endo~ nuclease integrace genes will also be discussed. 116.3 Simon Wain-Hobs on , Genetic Variability of the AIDS Viruses. Institut Pasteur, Paris, France. ABSTRACT NOT AVAILABLE AT TIME OF PRINTING T 15 4 The Irmnunobiology of the External Fmvelope Viral Glycoprotein ' ' J. MATTHEWS", scorr D. PUTNEY", JAMES R. RUSCHE", ROBERT c. mum", DANI P. BOIJOGNESI", “mke University Medical Center, Durham, NC, “Repligen Corporauon, Boston, MA, *"National Institutes of Health, Bethesda, MD The interaction of gplZO with the CD4 surface lymphocyte marker is critical for the processes of virus infection and Virus mediated cell/cell fusion. We have examined the relationship between the segments of gplZO responsible for each of these activities as well as those serving as target epitopes for virus neutralization. These results will be discussed in terms of vaccine and interventive strategies for the disease. 62 [16.5 manna. 1m: urn-no: AGAINST AIDS vums m amass D. Zagury, Z. Lurhuna, K. Mbayo, J.J. Salaun, R. Leonard, J. Bernard, M. Fouchard, B. Reveil, B. Goussard, J. Hana. Universite Pierre & Marie Curie (Paris) - Institut J. Godinot (halal) — Faculte de Msdacins de Kinshasa et INF! (Kinshasa). The diversity of subtypes of human immunodeficiency virus (HIV) represents a major difficulty in the immune defense unchanlsn- against AIDS because s hanoral response induced by one HIV strain may generate neutralizing Abs only against that strain and not against other HIV strains. That prompted us to investigate whether a cell mediated inflame response (ml) would overcome the subtype diversity limitations. Previous studies showed that infected T cells proceed, before release of virions, through an innunogenic stage, where the cell may a) trigger a CHI and b) represent a target for a specific cytotoxic T Cell (CTL). These data rationalize our operative strategy, to trigger a CH! against HIV infection by either non infectious fixed antologoua cells expressing HIV antigens at the cell surface (for saropositive hnuuu deficient organisms) or a vsccinla recombinant (Vr) expressing Gp.160 521 protein from RTLV.IIl—B (for aaronagativs organisms). After preliminary experiments on mnkeys showed the innocuity of both treatments, we treated by their fixed cells infected in vitro, 2 volunteers AFC patients, folloued 3 months after, by 8 others. No clinical coaplication whatsoever occurred up to now and immological parameters improved significantly. We also ilnmnized with Vr a saronegative individual (D.z., one of us) no clinical manifestation nor immunological defect occurred during the illumination. Vs than inunizsd 10 individuals high risk seronegative inlmnologically normal individuals. all volunteers. n.z. and these individuals presented a normal vaccine course without any ccnplication. In our presentation we will report the results of clinical and biological follow up and the degree of the innune response against different strains of HTLV.III. Finally we will discuss the scientific, ethical and economic conditions required for clinical trials of vaccines against HIV. All these researches have the full support of the Zairian Executive Council and its Ethics Cunnittee. Poster Session Correlation between Metabolism and Antiratroviral Effect of AzddThd TP.1 ( T) and ddCyd in Murine sad Human Call Syitsms 2 vitrg and E vivo. JAN gwpll , R. PAUWELS , M. BABA , E. DE CLERCQ , S. BRODER and D.G. JOHNS . aga lgtitute for Medical Research. varsity of Lauvan, 3-3000 Lauvan, Belgium; Clinical Oncology Program and avelopmental Therapeutics Program, National Cancer Institute, NIH, Bethesda, MD 20892, U.S.A. 2',3'-Didaoxycyt1d1ne (ddCyd) is superior to 3'-azido—2',3'-dideoxythymi- dine (Azdd’l‘hd) in suppressing the _i_g vitro infectivity of human imunodefician— cy virus (HIV) in human ATH8 cells. In contrast, Azdd'l'hd inhibits the H vitro transformation of 03H mouse (M0) cells by Moloney marine sarcoma virus (Ho-HSV) at an inhibitory dose (In 0) of 0.06 uh, that is at a concentration at least AGO—fold lower than the 111755 of ddCyd. Daily Azddl'hd treatment (125 walks/day) of mi mice infected at 3 ‘days after birth with Mo—MSV almost completely pre- vented MSV-induced tumor formation and resulted in a complete survival of the mics. At 25 mg/kg/day, significant delay in tumor formation and considerable prolongation of the life span of the mice was observed. In contrast, ddCyd treatment at 125 or 25 mg/kg/day only resulted in a slight delay of tumor for- mation, without any effect on the survival rate of the mica. Since AzddThd-5'- triphosphats (AzddTTP) and ddCyd-5'-triph03phate (ddCTP) are asstmad to be the active antiretroviral metabolites in the cell. we compared the levels of these metabolites in human and murins cells. Undu- sinilar experimental conditions. lower ddCTP but higher AzddT’l‘P levels were observed in murine 1.1210 cells than human ATH8 cells. Thus, the antirstroviral affect of Azdd’l‘hd and ddCyd corre- lated well with their corresponding intracellular 5'-triphosphats levels. The- se findings strongly suggest that the intracellular levels of the 5'-triphos- phate metabolites of 2',3'-d1deoxynuclaoa1das determine their efficacy for in- hibition of rstroviral infections and that the potency of these agents are greatly influenced by cell type dependent metabolism. TEZ A Model of Human Imunodeficiency Virus (HIV-l) ALBERT F.8YKDVSKV, Institute of Epidemiology and Microbiology, Moscow, U.S.S.R. He‘have carried out a comparative study of various strains of HIV-1, such as: LAV (obtained from Prof.L.Montagnier, InstitutGPesteur, Paris, France), HTLV-lll (from Dr.R.Gallo, Bethesda, USA), ARV (from Dr.J.Levy, San-Francisco, USA), the latter two were received from Prof.V.M.Zhdanov. The molecular organization of sub- virion components of HIV-1 was examined using the high—resolution electron micro- scope. we studied as components as the core, ribonucleoprotsin, the reverse trans- criptase, gp 120, gp 41, p 2a, p 18 and p 13. The diameters of the viz-ions with single core were about HAD—160 nm, but. the diamatm of the visions with two cores were about 200-250 nm. The cores were rod— or conic—shaped and usually were located excentricslly. Rod— shaped cores had the size of 130-150xh0—50 nm, conic cores had the height of 100- 130 nm and the diameters of 60—70 nm in the upper suit and 10—15 nm in the been one. The core shell contained spherical structures with the size of 6-7 nm x 3—4 nm. The nucleoids, consisting from ribonucleoprotein threads (2 nm in diameter), were packaged in special way into loops (diameter of 5-6 nm). The intermediate layer of virions contained globular structures (2-3 nm). Sphe- rical structures on the surface of visions (10-11 run) contained central channel (2 nm). "Minimal forms" of HIV-1 (diameter 50-70 nm) were also found. The visualization of components of HIV-1 let us construct a stereo model of the virus. TUESDAY, JUNE 2 T83 Monoclonal Antibodies to Peptides of the gp41 Molecule Neutralise Variapt Isolates of HIV * A.G. DALGLEISH,‘R.C. KENNEDY , P.C. CLAPHAM , T.C. CHANH , G.R. DREESMAN and M. MALKOVSKY, Retrovirus Research Group, MRC Clinical Research Centre, Watford Road, Harrow, Hiddlesex HA1 3UJ, England; Department of Virology and Immunology, Southwest Foundation for Biomedical Research, San Antonio, TX 78284, USA; *Chester Beatty Laboratories, Institute of Cancer Research, Fulham Road, London SW3 6J3, England. We have previously shown that rabbit antibodies raised against HIV envelope peptides neutralise virus infectivity in vitro (Chanh et a1., EHEO J. 5, 3065-3071, 1986; Kennedy et al., Science 321, 1556-1559, 1986). We how’show that monoclonal antibodies against 3 different gphl peptides all neutralise different isolates of HIV as determined by syncytia, pseudotype, reverse transcriptase and long term infectivity assays. This data has important implications for the development of anti-HIV vaccine. * TR4 In Vitro Infection of Primate Lymphocytes by HIV-1 and Expression 6? C51 Epitopes .MVRA 0. McCLURE*. Q. SATTENTAU**, P. BEVERLEV**. J. HEARN***, .J. ZUCKERM N****, R.A. WEISS, *Chester Beatty Laboratories, **Department of Human Tumour Inmunology, University College London, ***Institute of Zoology, ****Department of Medical Microbiology, London School of Hygiene and Tropical Medicine, London. Peripheral blood monoclonuclear cells (PMB) from a number of primate species were infected jg vitro with HIV-L PBM were phenotyped for expression of epitopes of the CD4 antigen with a panel of CD4 monoclonal antibodies (Mabs) by indirect inmunofluorescent staining and FACS analysis. The greater the divergence of the primate species from man, the fewer epitopes were conserved, and only one epitope was consis- tently represented in all species tested. This could be detected by the CD4 Mabs leu 3a, MT310, F101-65 and 94b1, all of which strongly inhibit the virus CD4 interaction in human cell lines. Infection of the primate PBM with super— natants of HIV-1 was tested after stimulation with PHA and IL-2. Samples of infected PBM or supernatants from these cultures induced a cytopathic effect in the C8166 CD4+ indicator human cell line. Preliminary data also show induction of RT activity in infected PBM and the presence of p18 by immuno- fluorescence. These data may indicate primate species which could be suscept- ible to infection. lg vivo tests are in progress. They may also indicate which part of CD4 is essential for virus binding. TE5 Characterization of a Monoclonal Antibody Specific for the HIV-1 Precursor Glycoprotein. E. KRUST‘, A. G. LAURENT , A. LE GUERN2 , 0. .JEANNEQUIN2 , L. MONTAGNIERl and A. G. HOVANESSIAN1 . lUnite d'0ncologie Virale, zHybridolab, Institut Pasteur, 25, rue du Dr. Roux, 75724 Paris Cédex 15, France. HIV-1 infected MOLT4-T4 cells provide an efficient system for the production of cellular precursor gp160 of HIV envelope glycoproteins, gp120 and gp41. The precursor gp160 was purified on an imuno-affinity column containing antibodies fromsera of HIV-l-seropositive patients. The precursor gp160 was then isolated by preparative polyacrylamide gel electrophoresis. Two out of 4 BALB/C mice inmunized with these purified preparations of gp160, developed specific circulating antibodies after 5 injections at 2 weeks interval. A hybridoma cell line was subsequently isolated producing monoclonal antibody (1961, K) specific for gp160. This monoclonal antibody can immunoprecipitate specifically gp160 present in HIV-l-infected cells. In an immune-blotting assay, it identifies mainly gp160 and manifests a slight affinity for the mature glycoprotein, gp120. The monoclonal antibody is probably directed against an epitope in the polypeptide residue of gp160 since it can recognize a 90,000 Mr deglycosylated polypeptide, product of gp160 digestion by Endo H. It does not cross-react with any protein of HIV-2 by imunoblot or immuno- precipitation assays. By virtue of its specificity, the monoclonal antibody might provide a powerful probe to detect gp160 in cells and tissues which might express partially the HIV-1 genes. 63 THE Evidence for lentiviral etiology in an epizootic of lymphoma and immunodeficiency in stump-tailed macaques (Hacaca argtgidgg) LINDA g, flflfllm, llJi. , I. JENNINGS“, J. m“, A. UYBDA‘", I. GARDNER", et a1., *California Primate Research Center, "Schools of Veterinary Medicine and Medicine, University of California, Davis, CA, USA. Infections of nonhuman primates with simian T—lymphotropic lentiviruses (S'I'LV—IIIs) serologically related to HIV and HIV-2 provide important models for human AIDS. Reports in the literature suggest that these viruses are endeaic in some populations of African monkeys, 9.21. African green monkeys (Cercopithecus gethigg) and sooty mangabeys (Macadam a_ty§), but do not cause disease. Natural infections in captive macaques are rare but inocula— tion of macaques with isolates from macaques or African monkeys causes an AIDS-like disease. Retrospective studies of a naturally occurring epizootic of immunosuppression and lymphoma in stump—tailed macaques (Stu) that oc- curred between 1976 and 1978 at the California Primate Research Center have revealed that sets from many Stli reacted strongly with HTLV-III (HIV); LAV-2 (HIV-2); STLV-III (macaque and sooty mangabey). None of the sets reacted with the simian immunosuppressive t D retroviruses which are the common cause of epizootic simian AIDS (SAIDS in macaques in the u.s. Inoculation of a juvenile rhesus (L mulatta) with a lymph node homogenate from a St! that died in 1977 of lymphoma produced lymphadenopsthy and decreased Til/1‘8 ratio. The animal developed antibodies cross reactive with human and simian lymphotropic lentiviruses. Virus recovered from this rhesus had llg++ depend- ent reverse transcriptase and the ultrastructure of a lentivirus. This documents the first naturally occurring propagating epiaootic of lentivirus associated SAIDS in captive macaques and provides an additional isolate for comparison with known human and simian lentiviruses. TPJ Absence of HTLV-IV in Central Africa PHYLLIS KANKI*, J. ALLAN*, F. BARIN“, M. ESSEX*, *Harvard School of Public Hea tfi, Boston, MA, “University of Tours, Tours, FRANCE. HTLV-IV was first described in Senegal and has been shown to be prevalent in most countries of West Africa where reports of AIDS cases are still infre- quent. In contrast, AIDS and HTLV-III/HIV are observed at high and increasing rates in discrete regions of Central Africa. This study was conducted to assess the prevalence of HTLV-IV in 7 countries of Central Africa and to determine any association with AIDS or a related disorder. Serum samples from healthy controls, tumor patients, ARC, tuberculosis, STD patients, and AIDS were kindly provided to us as a collaborative study with T. Quinn, N. Clumeck, F. Mawovondi, I. Lausen, D. Zagury, L. Thiry, J. Craighead, C. Saxinger, and L. Falk; Zaire, Cameroon, Zambia, Kenya, Tanzania, Burundi, and Uganda were represented in the sample population. All 1,430 serum samples were analyzed by radioimmunoprecipitation and SDS/PAGE and immunoblot for antibodies to HTLV-IV. The cross-reactivity between HTLV-IV and HTLV-III/HIV antigens has been well documented and appears to be the strongest in a and 01 encoded antigens. Therefore, a positive HTLV-Iv response was dist nguishe y a specific response to the env antigens of HTLV-IV, the gp160/120 and gp32 (transmembrane). NONE of the 17430 samples analyzed demonstrated antibodies to the gn_v-related antigens of HTLV-IV; in HTLV-lII/HIV antibody positive samples, cross-reaction to the g_a_g_ and PE. antigens of HTLV-IV was frequently observed. HTLV-IV was not detected in 7 Central African countries surveyed, whereas HTLV-III/HIV in association with AIDS and related disorders was quite common. Further study on these two viruses of apparently differing pathogenicity will be important to our general understanding of various members of the HTLV family and how they have evolved. TEs HIV Infection of B Lymphoblastoid Cell Lines JAMES E. nonaoc*, G. LENOIR**, c. MULDER*, *ums, Worcester, MA, USA, **International Agency for Research on Cancer, Lyon, FRANCE We examined the susceptibility of B Lymphoblastoid cell lines to HIV infec- tion. A series of EBV genome-negative and EBV‘converted Burkitt Lymphoma cell lines, and other EBV-infected cell lines, exhibiting both permissive and non- permissive EBV infection, were studied. Initial studies showed that only 1 of 4 EBV—negative Eurkitt Lymphoma cell lines and 10 of 20 EBV-positive cell lines could be infected with HIV-IIIB. HIV infection was monitored using re- verse transcriptase and cytoplasmic RNA dot-blot assays. Further studies using two different strains of HIV (1113, RF) and a LAV 2 strain (Moi-532) followed. The C-8166 syncytia assay was also used to moni- tor infection. Twenty-two of 2A cell lines could be infected with at least one of the three virus strains. In certain cell lines, virus production was very low and detectable only by the syncytia assay. Each cell line which could be infected with HIV was found to express T4 surface antigens. It is clear from this study that prior EBV infection has no major effect on HIV susceptibility. Southern blot analysis of DNA extracted from long-term, HIV-nonproducing cell lines detected integrated HIV genomes. This study in- dicates that Tq-positive B lymphoblastoid cells may serve as a reservoir for latent HIV infection, even in the absence of EBV infection. TUESDAY, JUNE 2 TPg Detection of HIV—Specific Sequences Using i3 Vitro ' Nucleic Acid Amplification and Oligonucleotide-Based Affinity Chromatography THOMAS E. GINGERAS*, D.D. RICHMAN**, G.R. DAVIS*, AND D.Y. KWOH*, *The Salk Institute Biotechnology/Industrial Associates, Inc., La Jolla, CA, USA, **University of California, San Diego School of Medicine, La Jolla, CA, USA. The polymerase chain reaction (PCR) protocol, first described by Siaki gt il' [Science (1985) 232:1350-1354], permits a 10“— fold increase in the copy number of a 350 bp region from the en! gene of the HIV RNA genome. The products of this i3 vitro ampli— fication can be labeled by incorporation of 32P—dCTP during the last cycle of amplification. Although the labeled nucleotides can be incorporated into both HIV-specific and human—host cell—speci— fic sequences, the labeled HIV—specific fragment can be detected by a rapid and simple hybridization procedure using support—bound, HIV—specific oligonucleotides. This protocol has been applied to the detection of HIV present in cultured cell lines (CEM) and in clinical samples derived from a longitudinal study of a cohort of 240 homosexual men at various degrees of risk for AIDS. Results from the application of this detection protocol to these samples will be discussed. TP10 Imunoaffinity Purification of the Major Envelope Glycoprotein from ' HTLV-III-Infected H9 Cell Culture Media. STEPHEN H. PYLE*, W.G. ROBEY**, J.W. BESS, JR.*, P.J. FISCHINGER**, R.V. GILDENi, L.O. AHTHUR*, *Program Resources, Inc., NCI-Frederick Cancer Research Facility (FCRF), Frederick, MD 21701, **0ffice of the Director, Virus Control Unit, NCI-FCRF, Frederick, MD 21701, USA. Purified external envelope glycoprotein, gp120, of the human immuno- deficiency virus (HIV), the name proposed for the retrovirus causually assoc— iated with acquired immune deficiency syndrome (AIDS), has been shown to induce the formation of neutralizing antibodies when inoculated into laboratory animals and is, therefore, being evaluated as a prototype vaccine. The gp120 is not tightly associated with the virus and is shed into the culture fluids used to propagate HTLV-IIIb—infected H9 cells. We have utilized an immunoaffinity resin, prepared by coupling IgG from AIDS patient sera to Sepharose 43, to purify gplZO from this culture fluid. In a typical run, virus is removed from the culture fluid by continuous—flow ultra—centrifugation, and 144 liters of the fluid is chromatographed over the immunoaffinity resin. After washing, bound HTLV-IIIb envelope glycoprotein was eluted with low pH buffer. Following extensive dialysis against distilled water, the gp120 was further purified by polyacrylamide gel electrophoresis, HPLC or differential precipitation. This purified gplZO induced both precipitating and neutralizing antibodies in laboratory animals and will provide a valuable reagent in AIDS vaccine research and HIV envelope studies. Research sponsored, at least in part, by the National Cancer Institute, DHHS, under Contract Number N01-C0—23910 with Program Resources, Inc. TP11 Expression in E. coli of open reading frame gene segment: of Human ' B—lymphotropic virus (HBLV) MING-CHIU FUNG*, S.C. FUNG*, S.F. JOSEPHS**, M.L. BERMAN***, F. WONG-STAAL**, NT—CHANC;,_*FEylnr College of Medicine, Houston, TX, **National Cancer Institute, National Institutes of Health, Bethesda, MD, ***Bionetics, Inc., Kensington, MD. Human B-lymphotropic virus (HBLV), a new member of the herpesvirus family, has been recently detected in several patients with lymphoproliferative disease including the chronic mononucleosis fatigue syndrome. Several subgenomic fragments of HBLV have been molecularly cloned into bacterial plasmids and partially characterized. A combined cloning/expression protocol was used to identify a gene encoding a viral protein that is immunoreactive with sera from patients infected with HBLV. Random fragments were generated from the HBLV subgenomic DNA derived from pZVHlA by DNase Bal 31 digestion or sanitation were inserted into an expression vector pMLBllll and the HBLV DNA sequences were expressed as proteins fused to fi-galactosidase. Several different open reading frames were mapped along the subgenomic DNA fragment. Sera from patients infected with HBLV were used to screen for HBLV immunoreactive fusion proteins. Two expression plasmids were isolated and theirspecific fusion proteins were identified with patient sera in the Western blot analysis. The HBLV DNA sequences represented in these two clones were mapped within a single open reading frame on the HBLV genome. Using affinity chromatography and SDS—PAGE, the HBLV-fl-galactosidase fusion protein waspurified and monoclonal antibodies were raised against them in mice. TB12 Western Blot Assay Patterns of Early Antibody Response to the Human Immunodeficiency V1rus. Patr1c1a E. To lor, Cladd E. Stevens and Pablo Rublnsteln, The New York Blood Center, New York, N.V., U.S.A. Stored serial serum samples from 103 homosexual men who participated 1n hepatitis B vacc1ne efficacy trials begun in late 1978 and who showed serocon- version during the subsequent 8 year period for antibody to the human Immune- deficiency virus (anti-HIV) were tested by the enzyme-linked Immunosorbent assay, ELISA, (Dupont Inc.). Sera obta1ned at and three to six months prior to anti-HIV positivity by ELISA were also examined by Western Blot (WB) pro- cedure (Blotech Laboratories, Inc.). The NB patterns for 59 of these men showed anti-HIV reactivity for p24, p41 and other HIV proteins at the same time as ELISA reactlvlty was first observed. The remainder showed diverse patterns of early anti-HIV reactivity, the most common be1ng antl-p24 reacti- vity with or without anti-p55. In 12 men anti-p24 was the first antibody to HIV to appear by WB. In five of these the ELISA result was negative when anti-p24 appeared and, in another, ELISA gave a positive reaction in a serum sample taken two months before the anti-p24 positive sample. The remaining seven were both ELISA and WB posltlve. The appearance of antl-p55 preceded anti-p24 and other antibodies In six instances. Anti-p41 was not found before the appearance of antI—p24 or antl-p55 or before antibody was detected by ELISA. No relat1onship was found between the pattern of early anti—HIV response as observed by WB and the T helper to T suppressor cell ratio obtained in early 1984 when studies of cell-mediated immunity were initiated. 'TP13 Demonstration of Antigenic Variation in HIV Envelope Proteins by ' Competitive Radioimmunoassays. 44w. BESS, JR.*, 5.". PYLEt, AND L.0. AHTHUHt, *Program Resources, Inc., NCI— Frederick Cancer Research Facility, Frederick, MD 21701, USA. Competition radioimmunoassays have proven extremely useful not only in quantitation of biologicals but for establishing immunological relationships as well. We have purified the outer envelope glycoprotein (gplZO) of HTLV—IIIB and used it in establishing competition radioimuunoassays. A broadly specific immunoassay was obtained when HTLV—IIIB gp120 was used as the radiolabeled probe in a competition assay with serum from an AIDS patient. All HIV variants tested in this assay competed completely with equal efficiency providing an assay for quantitating gp120 in viruses and other biological samples. Use of antisera generated against purified HTLV-IIIB to precipitate 125—1 HTLV-IIIB gp120 provided an immunoassay which differentiated HIV variants. HTLV—IIIB competed completely in the assay while the variant HTLV—IIIRF gave only partial competition. Use of these radioimmunoassays, along with an HTLV-IIIRF gp120 currently being developed, will provide rapid sensitive assays for establishing HIV envelope relatedness. This information, coupled with data from envelope nucleotide sequencing data and cross—neutralization results, will be potentially invaluable in assessing HIV isolates to be used in vaccine strategies. Research sponsored, at least in part, by the National Cancer Institute, DHHS, under Contract Number N01—CO—23910 with Program Resources, Inc. TP14 Topographical Analysis of HIV p24 using Monoclonal Antibodies ' KEVIN J. REAGAN, A. L. PIEPER, M. A. WALSH and R. L. TYSON, E. I. Du Pont de Nemours and Co.. Inc., Medical Products Department, Wilmington, DE 19898. We have prepared panels of monoclonal antibodies reactive with the major internal core protein (p24) of Human Immunodeficiency Virus (HIV). Balb/c mice were immunized with partially purified virus or isolated viral proteins and immune Splenocytes fused with variant 653 or P3x63 A98 mouse myeloma cells. Reactive hybridomas were initially screened on Du Pont HTLV—III ELISA plates. A further characterization of antibody specificity was accomplished by Western Blot reactivity with electrophoretically separated virus, surface and cytoplasmic immunofluorescence on virus-infected H9 cells and reactivity with recombinant core proteins. Over 20 monoclonal antibodies specific for the p24 core protein were isolated and used to construct a functional epitope map. We identified four reactivity patterns representing three distinct antigenic sites on this protein. TUESDAY, JUNE 2 TB15 Complete Type III Human T—Lymphotropic Viruses GENOVEFFA FRANCHINI, et al., Laboratory of Tumor Cell Biology, National Cancer Institute, NIH, Bethesda, MD. A new primate retrovirus, simian T-lymphotropic virus type III (STLV-III), recently has been isolated from healthy African green monkeys and is apparently non-pathogenic in its natural host. However, spontaneous infection and inocu- lation of STLV—III into Macaque monkeys induce a disease like human AIDS. Independent isolates of human retroviruses related to STLV-III have been obtained from healthy individuals (HmIM—IV) and patients with AIDS (LAV-Z SBL-6669) from west Africa. We molecularly cloned the STLv-III genome and generated probes from the gag and envelope genes and determined genetic relatedness by Southern analysis of these simian and human retroviruses. our results indicate that all these retroviruses are genetically closely related to each other. HTLV-IV and STLV-III genomes differed only in 2 of 15 restriction enzyme sites while LAv—2 and ESL-6669 exhibited greater polymorphism as compared to HTLV-IV and V—III. Computer analysis of the nucleotide sequence obtained from the cloned STLV—III genome in comparison to that of HTLV—III showed a high degree of homology, suggesting common ancestry of these two viruses. Comparison within specific viral genes has allowed characterization of biologically important regions within the env gene and functional domains of some of the genes encoding regulatory proteins for the AIDS and AIDS related Viruses. Nucleotide Sequence of the simian T—Lymphotropic Virus and Genetic Analysis of a New Subgroup of AIDS—Related F6 and TR16 Phorbol lZ-Hyristate Iii-Acetate Enhances HIV Promoted Gene Expression and Acts Upon a 12 Base Pair Functional Enhancer Element. JOSH D. KAUFMAN. G.S. BUSHAR, C.P. 6131, AND H.A. HORCROSS, Division of ViroloSY, FDA. Bethesda, MD. USA Phorbol 12-myristate la—acetate (FHA) is a potent inducer of T-cell immune functions and has recently been demonstrated to increase viral replication in cell lines infected with Human Immunodeficiency Virus (HIV). In order to define sequences required for viral induction by PHA, cell lines were transiently transfected with viral long terminal repeat (LTR) sequences directing chloramphenicol acetyl transfersse (CAT) gene expression. 10 ng/ml PHA added to transfected cell cultures 24 hr before harvest reproducibly increased both CAT mRHA and enzyme expression 2 to 5 fold. Induction of CAT expression occurred in T—cell lines. monocyte lines. and cultured peripheral blood lymphocytes. Sequences necessary for basal and PHA induced levels of CAT expression were determined by transfecting cells with’deletion mutants constructed from the original LTH—CAT expression plasmid. Removal of U3 DNA 118 base pairs (bp) upstream of the mRHA start site improved basal and induced levels of CAT expression up to 5 and 50 fold. respectively. Deletion of DNA 68 bp upstream of the mRNA start site eliminated the basal expression level and prevented FHA induction. Basal and induced levels of CAT expression were restored by introducing a synthetic oligonucleotide containing a 12 hp LTR sequence. The enhancer-like sequence could be inserted at a site distal to the CAT gene open reading frame and functioned in a position and orientation independent manner. In summary, the data defines a transcriptionally active and PHA inducible regulatory/enhancer element critical to the control of HIV gene expression. T217 Inhibition of HIV by Species of Recombinant Interferon Alpha VICKI MASISON*, M BRUNDA**, P GAGE**, J GROOPMAN*, *Divlsion of Hematology/Oncology, New England Deaconess Hospital, Harvard Medical School, Boston, MA; **Hoffman La Roche, Nutley, NJ It has previously been reported that recombinant interferon alpha-A has a dose-related suppressive effect on HIV replication in peripheral blood mononuclear cells in vitro. Based on this initial work, we investigated the effects of 6 species of recombinant human interferon alpha on HIV (HTLV-III B strain) infection of the T lymphocyte cell line H9 and the monocytoid cell line U—937. Both cell lines were mycoplasms free and maintained an RPMI 1640 with 20% fetal calf serum. Cultures were treated with either a single dose or multiple doses of recombinant interferons alpha A, A/D, C, K, I, or D at concentrations of 16, 256. and 1024 U/ml. Viral infection of target cells was quantitated by indirect immunofluorescence and reverse transcriptase (RT) activity in H9 on days 7 and 11 and in U937 on days 14 and 18. A dose response for HIV inhibition was seen with all species of alpha interferon. Single doses of interferans A, A/D, K, and I at 1024 U/ml completely inhibited HIV replication in both H9 and U937. Interferons alpha C and D were less inhibitory by 1-2 logs of RT activity. Approximately 50% inhibition of HIV infection was seen at 256 U/ml. Multiple doses of all six alpha interferon species were effective in U937 cells with total suppression seen with all species at 1024 U/ml. Cell viability was not impaired with interferon therapy; indeed, the survival of both H9 and U937 cells was improved by 10-25% in the presence of 256—1024 U/ml of interferon. These studies demonstrate that the interferon alpha family has antiretroviral activity in vitro in lymphoid and monocytoid cell systems and may be clinically useful in the therapy of AIDS. 65 T218 Synthetic peptide analogs of HIV proteins are recognised by naturally ac uired antibodies. D.STAPLET0N1, S.CUMMING , D.MCPHEE2, B. KEMPl, R.DOHERTY2. 1: Department of Medicine, Repatriation General Hospital, Heidelberg, VIC. 2: Department of Virology, Fairfield Hospital, Fairfield, VIC. AUSTRALIA. Predicted amino acid sequences of HIV proteins were scanned for potential antigenic epitopes using the Welling Antigenicity program (FEES lett. 188, 215-9, 1985). Conserved, hydrophilic sequences identified were synthesized as 13-21mer peptides using automated Merrifield solid phase techniques. Peptides synthesized included gp120(2-13), gp120(55-65), gp41(582-596). gp41(579-600)s gp41(659—670), 8p41(766-778). ptat(60-72), and ptat(46-58). Peptides were studied by ELISA for recognition by human antibodies. A11 peptides could be recognised, with sera from 98% of viraemic patients recognising gp41(579-600), and 732 of identical sera the truncated form (582-596). These results concur with those of Wang et al (PNAS, 83,6159- 6163, 1986). Ptat(60—72) was recognised by 522 of sera from viraemic patients. Serum from one viraemic patient with antibodies against core proteins only on immunoblot assay did not recognise any of the peptides. Individual profiles of recognition of peptides did not vary over time, but differed substantially between individuals . These findings demonstrate the significance of natural variability of HIV isolates, and offer a means of further defining conserved, immunogenic epitopes for serodiagnosis or vaccine development. TP19 Chronic Infection of Non-human Primate Gibbon Ape (W E) by Human Immunodeficiency virus (HIV), HTLV-IIIB. P.D. MARKHAM’, W. JARRETT", E. GARD‘, M.G. SARNGADHARAN’, and R.C. GALLO’*‘. *Department of Cell Biology, Bionetics Research, Inc., Rockville, MD; ‘*Department of Veter- inary Pathology, University of Glasgow, Scotland: ""Laboratory of Tumor Cell Biology, National Cancer Institute, Bethesda, MD. Many attempts have been made to identify animal model systems suitable for the study of pathogenesis resulting from infection by HIV and its prevention on treatment. To date, the persistent infection and immune response following inoculation with virus or tissues from AIDS patients had been documented in only one animal, i.e., chimpanzee (£52 troglodytes) (1,2). We describe here the extension of these observations to an additional non-human primate, the gibbon ape (Hylobates 133). The infection, recognized by isolation of infec- tious virus from peripheral blood mononuclear cells and appearance of specific antibodies, was detected within two weeks following i.v. inoculation with concentrated HTLV-IIIB, and has persisted for several months. During this period of time, other than possible lymph node involvement, no noteworthy pathological symptoms were detected. In parallel experiments, animals from three other primate species, i.e., Rhesus monkey (Macaca mulatta), African green monkey (Cercopithecus aethiops), and common marmoset (Calithzix jacchus jscchus), gave no evidence of infection and only sporadic or transient immune response was observed. 1. Alter, H.J., Eichberg, J.W., Masur, H., 35 El.,.Lancet i£2549, 1984. 2. Francis, D.P., Feorino, P.H., Broderson, J.R., 35 51., Lancet ££:1276, 1984. T220 A Possible Role for Bpitopes, other than CD4 in the Receptor Complex for (HIV). D.V. ABLASHI', P.D. MARKEAM", 5.2. SALAHUDDIN‘, F. VERONESE", AND H.C. GALLO’, *National Cancer Institute, Bethesda, MD., **Bionetics Research, Inc., Rockville, MD. It was demonstrated that the receptor for HTLV-III on T—helper lymphocytes includes the CD4 protein complex. However, we have demonstrated that EBV genome positive B-lymphocytes can be infected by HTLV-III regardless of the presence of CD4 detectable by immunofluorescence of immunoprecipitation pro- cedures. To further investigate these observations, monoclonal antibodies directed against multiple CD4 epitopes were used to compete with HTLV-III infection of two highly susceptible lymphoblastoid cell lines. This treatment failed to completely block HTLv—III infection of either CD4- or CD4+ B cell lines at concentrations that completely blocked the infection of CD4+ T-cells including fresh leukocytes from human peripheral blood and established T cell lines. B-cell specific monoclonal antibody (ORB-7) blocked EBV infection of B-cell lines but did not block infection by HTLV—III, suggesting that HTLv-III does not use the EBV receptor. These observations further suggest that CD4 proteins are not required for the infection of all susceptible target cells. However, the presence of these epitopes may constitute a high affinity recep- tor for HTLv-III. Concerning susteptable B-cells, EBv may code for or induce the synthesis of molecules that fulfill the receptor function. TUESDAY, JUNE 2 11321 Immunological and Chemical anal sis of H'l'LV-III p15 ' r. diMARZO vskotlassl, R. RAHMAN , 'r. CopELANDz, s. OROSZLAN2, R.C. GALLO3, M.G. snucansaml, lslonetics Research, Inc., Rockville, MD; 2Lab. of Molecular virology and Carcinogenesis, NCI-PCRP, Frederick, MD, 3Lab. of Tumor Cell Biology, NCI, Bethesda, MD. The first open reading frame of HTLv-IIIB genome has been identified as the 33 gene. The proteins encoded by this gene are p17 as the amino terminal protein, p24 as the middle peptide and p15 as the carboxy terminal end. a monoclonal antibody recognizing p15, designated M35/2F8 has been developed and used to further characterize this protein. p15 was purified from an extract of H9 cells producing HTLV-IIIB by an immunoaffinity procedure employing immobilized purified Has/2P8 IgG. in addition to p15, M35/2F8 purified the precursor of lag proteins p53, a smaller intermediate p39, and at a lesser concentration a very small peptide of approximately 6 kn. In contrast, M35/ 2P8 purified only p6 when viral extract was applied to the immunoaffinity column. H9 cells producing HTLV-IIIB were then labeled with [35sl-cysteine and [3al—leucine, illmunoprecipitated with M35/2P8 and analyzed by SDS—PAGE. No immunoprecigitation of p6 has been observed when cells or virus were labeled with I 5Slmcysteine. However p6 was distinctly immunoprecipitated when [3l-ll-leucine labeled cells were analyzed. These results demonstrated: that m p15 is indeed processed into two smaller products p7 and p6 as anti- cipated, that ass/2n recognizes an epitoprorthe cysteln'efre‘e’pe‘ptids’pd and that p6 arises from a maturation cleavage of p15. To confirm its viral origin, [3H1—leucine labeled p6 was subjected to radiolabel sequencing. Leucine was unambiguously assigned at position 1 and 13 of the 40 cycles examined. The amino acid sequence determined is a perfect match with a pre- dicted sequence at the carboxy terminus of the gig gene starting with Leu‘“. TR 22 Interaction of Human Immunodeficiency Virus with Neural Cells Isolated from the Human Fetus Nervous System BRIAN fllfiDAflL“, Rhonda A. Guyton“, Luzi A. Pfenninger“, and From S. Satin“, *The Pennsylvania State University College of Medicine, Hershey. PA, USA,“ Laboratory of Tumor Cell Biology, National Cancer Institute, Bethesda, MD, USA. Human immunodeficiency virus (HIV), the primary etiological agent of acquired immunodeficiency syndrome (AIDS), has been implicated in the causation AIDS-associated neurological dysfunction and may be responsible for an increasing number of neonatal immunologic and neurologic disorders. However, as yet there is no model system available to investigate the interaction of HIV with the developing human nervous system in vitro. To examine the intracellular events associated with HIV infection of the human fetus nervous system we infected cells obtained by enzymatic dissociation of aborted human fetus dorsal root ganglia and their attached spinal roots and nerves. The expression of the HIV gag gene protein products (p17 and p24) was detected in a subpopulation of cells with a non-neuronal morphology, reaching a maximum within 3 days. Although 70% of the non-neuronal neural cells were p17- and p24-positive 3 days after infection, a majority of the cell population survived acute HIV infection, with the expression of p17 and p24 decreasing below the limit of detection by 12 days postinfection. Additional studies have demonstrated that the number of HIV-pl7/24 nonneuronal neural cells detected 3 days postinfection decreased in direct correlation with increasing time of in vitro maintenance of the human fetus neural cells prior to HIV infection. These results suggest that in vitro maintenance of the neural cells after isolation from human fetus DRG and ad'accnt spinal root and peripheral nerves may result in plasma membrane alterations that inte ere with HIV attachment and/or penetration or an intracellular physiological change that impairs at least the expression of the gag gene protein products p17 and p24 after infection or possibly a combination of both. This system may prove useful for examining the neuropathogcnesis of HIV infection of the developing human nervous system . TP23 Glycosylatlon Inhlbltors Block the Expression and Functlon of HIV ' Glycoprotelns and Thelr Receptor(a) HERBERT A. stoucl-l‘» R. PAUWELS", E. or CLERco”, J. osswrrn”, J. coculaux'“. w. KENEALY'", ‘Unlvorslty of Pcnnsylvanla School of Medlclne, Phlladelphla, PA, "Kathol|eke Unlvorsltelt Leuvsn, Bolglum, "’Inat|lut Pasteur du Brabant, Brussels. “"E.l. DuPont Central Res., WIlmlngton. DE The Intoractlon of envelope glycoprotolns of HIV (99110 and gp41) and thslr rocoptor(a) ls responslblo for vlral entry and cell fusion; 2-deoxy-D-glucose (2—dGlc) blocks the expresslon of HIV glycoprotolns. Unlnfectod MT—4 or CEM cells were treated wlth 5-10 mm 2DG|c for 24-96 hrs. One—half were Infected wlth HTLV3_B; an untreated group of cells were slml- larly Infected. Fresh medlum (wlth or wlthout 2—dGIc) was added and the cells lncubated for an addltlonal 72 hrs. Trlton X-lOO-lysed cells or glutaraldehyde-flxod cell surfaces were lntoracted wlth polyclonal antlbo— dlas agalnst HIV-recomblnant protelns. (pwENVS, pENV14, pENV14, pENV120, pENV7),. Alternatlvely, unlnfscted cells were Interactod wlth monoclonal antlbodles I alnst T4: T4A. T8 and the IL-2 receptor. Bound antlbodles were guantlf ed with [‘25IJ-F(ab')2 fragments of antlmouso IgG or [125l1—antlgoat IgG (rabblts). By trypan blue oxcluslon and light mlcroscopy. 2—dGIc-treatsd calls were protected agalnst CPE by HIV. Treatment of MT-4 calls wlth 2—dGlc produced a 35% decrease In the blndlng of OKTAA (to the putatlve receptor) vs controls. Ualng [3HJ-Rlcln communla or gal oxldaso tochnlque wlth LI3HB4, we observed a 35-60% decrease In blndlng or labelllng of 9p41 or gpllO In dGlc-treatod-calls; thls was con— flrmad by P.A.G.E. or Western Blots. Those otudlel support the vlaw that glycosylatlon Inhlbltcrs block the lnltlal steps of HIV—Infoctlon and should prove useful In the treatment of AIDS. TP24 Human Immunodeficiency Virus (HIV): Fine Structure and Immunolo- calization of Virus Strucutral Proteins and HUI-Determinants. HANS R. GELDERBLOM M. UZEL, H. REUPKE, E.H.S. HAUSMANN, G. PAULI“, M.A. KGCH, Robert-Kochvlnstitut des Bundesgcsundheitsamtcs und *lnstitut: flit Virologie der Freien Universita’t Berlin, Nordufcr 20, D—rooo Berlin 65 Thin section electron microscopy (EM), serial sectioning and tilting experi— ments were applied to elucidate the fine structure of HTLV—lll B and LAV-z. On the envelope 7o - Bo knobs are observed having a diameter of 15, and a height of 9 nm. Knobs are arranged according to surface replica EM, in a T = 7] symmetry and are shed concomitant to the morphological maturation of HIV. Adjacent to the inner leaflet of the viral membrane an electron- dense matrix protein is seen which enlarges parallel to the long axis of the elongated prismatic viral core. The antigenic architecture of the virion was investi ated by pro-embedding lmmunofetritin EM and immunogold labeling of ultratfiin cryoscctions. The core shell shows tubular symmetry and p24 antigenicity, while p17 determinants are associated with the matrix protein: both were not detectable on the outside of the virion. The major envelope gplzo forms the knobs and gp41 represents the transmcmbrane protein. HLA-antigens were shown to be incor rated in the envelope corresponding to the antigenic make-up of the virus-pr ucing cell. Combining rfitfiphologicalfidlmnmnologital observations a structural model of HIV is proposed. TP25 An Assay for HIV-p24 Antigen With Chemiluminescence ' Detection Using Antibodies Against Synthetic Oligo- Peptide Fragments of the Major Core Protein HARTMUT ROKOS*, A.GADOW*, R.KUNZE**, B.SCHWARTLANDER**, B.FRENZEL"', W.RGNSPECK***, *Research Laboratory, Henning Berlin, Berlin, Germany, **Robert Koch—Institut, Berlin, **'Biochrom, Berlin. Antibodies against 2 separate epitopes of p24, the major core protein of the human immunodeficiency virus were obtained in sheep on immunisation with short synthetic oligopeptides. After purifi- cation by affinity chromatography, one antibody is coupled to polysterene beads as solid phase, the other to a diacyl hydrazide as chemiluminescence label. This Lumitest sandwich-type immuno— assay requires a one-step incubation at room temperature over- night. The assay protocol includes pretreatement with sodium dode- cyl sulfate for denaturation, thus minimizing risks in handling infectious material and reducing interference from human anti- bodies against p24, present in many sera, often leading to false results in other antigen assays In 9 out of 24 follow—ups of male homosexuals taking part in a prospective study, p24 antigen was detected up to 6 months prior to seroconversion. In serial samples of 1 additional patient who showed after seroconversion persistently very low antibody titers, p24 antigen was found always The assay can be used to determine LAV-Z in cell culture'super— natants, too, as these antibodies are highly cross-reactive with the p24 protein of this variant 1'st Inhibition of HIV reverse transcriptase activity by culture fluids ' from HIV-infected, Epstein-Barr virus-transformed cells. MICHEL TREMBLAY, M.A. HAINBERG, Lady Davis Institute for Medical Research, Jewish General Hospital, Montreal, Canada. Most individuals who are infected by HIV are also sets-positive for Epstein- Barr virus (EBV) and it is important to understand potential relationships between these two viruses. We used EBV progeny from the simian 3-95-8 cell line to infect and transform unstimulated cord blood lymphocytes. Following the establishment of EBV-transformed B cell lines, these cells were super— infected with the HTLV-IIIB strain of HIV. These cultures were examined periodically for viral reverse transcriptase activity, by means of a poly- ethylene glycol precipitation procedure, and for the presence of infra-cellular viral antigens, by an indirect immunofluorescence assay using mouse monoclonal antibodies against the HIV proteins p15 and p26 (kindly supplied by Dr. R.C. Gallo). By 17 days after infection about 152 of cells had become positive for HIV antigens, yet no RT activity could be detected in the culture fluids. To investigate this further, aliquots of viral pellets from the HIV-infected, EBV—ttansformed cells were mixed with equal volumes of similar material ob- tained from H-9 cells, continuously infected with HTLV-IIIB. RT activity of the latter preparations was inhibited by 881 when the assays were performed immediately and by 951 if the samples were allowed to co-incubate for 3 hr at 37°C. These data suggest that EBV or EBV infection may have an inhibitory effect on HIV RT activity. Supported by Health and Welfare Canada and by the Medical Research Council of Canada. TUESDAY, JUNE 2 TP27 Kinetics of HIV infection after IV exposure to blood from an ' AIDS patients. SOPHIE MATHERON*,D. DORHONT**,M.A. REY*,F. BRUN-VEZINET*,F. BOUSSIN**, SAIMOT*,*H6pital Claude Bernard, Paris, **CRSSA, Clamart, France. A 40 year old man was contaminated by IV injection (10 ml) of an AIDS patient‘s blood, from which HIV had been isolated. He developed clinical symptoms of primary HIV infection 23 weeks later. His virological status follow up was assessed by ELISA , Western Blot (W3) and PBL cultures (PBLC). A.G. Weeks PBLC ELISA WESTERN BLOT +)0.30 18 25 41 55 110 160 —40 - 0.036 — — - - — - IV 10 m1 ._) 0 8 ND — 0.016 — - - — — — 18 + ND 19 4» ND Clinical symptoms—)23 + - 0.133 + + - - — +/— 24 ND — 0.103 + + — +/_ _ +/_ 25 ND — 0.221 + + — +/- — +/— 26 + + 0.49 + + - ¢/— - + 29 ND + 0.45 + + +/— +/— — + 32 ND + 0.58 + + + + + + 33 ND + 0.907 Our data show after contamination : 1) positive PBLC at W18 ; 2) positive WB at the time of clinical symptoms (W23) ; 3) Positive ELISA at W28. 0n W33, the patient had not ARC nor AIDS. Tnzs A Rapid, simple and Economical Screening Assay for Antibodies to the Human Immmdelficiency Virus (HIV). * * &CARLSON , 5.9. MERTFNS , J‘L. YEE , M. JENNIARS ,*M.B. GARDNER , E.J. WATSON-WILLIAMS , J. GHl'ifiYEB AND Rn]. BIGGAR . Uniy; of California, Davis, CA., Centocor, Inc., Malvern, PA, Natl. Cancer Inst., Bethesda, MD. A dot enzyme immunoassay for the detection of anti-HIV antibodies was developed using an antigen derived from a recombinant HIV envelop protein, peptide 121 (Centooore, Inc., Malvern, PA). The assay can be performed in 30 minutes with a qualitative endpoint that does not require expensive instrumentation. Antigen was spotted onto opaque, high-impact polystyrene cards. The test was performed by adding human serum, plasma, lysed whole blood or saliva, alkaline phosphatase-conjugated goat anti—human IgG and substrate to the antigen spot with washing between reagents. A bright blue color developed on the antigen Spot for positive specimens, and negative samples yielded no color. Correlations of results with western blot (WB) were as follows: Specimens Source No. Tested/No. WB Positive 8Corre lation Serum/Plasma USA 118/60 99.2 Sew/Plasma Africa 103/50 98.6 Whole , lysed blood USA 115/50 98.3 Saliva USA 20/8 100 This assay may be useful for anti-HIV antibody screening for blood donors, epidemiologic studies or initial clinical assessment in remote areas of the world. szg Attempts to Produce a Progressive Immune Deficiency and ' Encephalopathy in Nonhuman Primates with the Human Immunodeficiency Viruses. R. YANAGIHARA, D.M. ASHER, A.V. WOLFF, C..7. GIBBS, JR., D.C. GAJDUSEK, et al. National Institutes of Health, Bethesda, lid. of the multiple nonhuman primate species we have investigated to date, including African green and marmoset monkeys, only chimpanzees (Pa_n troglodytes) and rhesus monkeys (Hacaca mulatta) are susceptible to experimental infection with the human immunodeficiency viruses (HIV). Chimpanzees develop persistent infection following intravenous and/or intracerebral inoculation with strains of HIV, with brain tissues and plasma from AIDS patients, or with blood from experimentally infected chimpanzees. None of 24 HIV-infected chimpanzees monitored for nearly three years has developed a wasting illness, neoplasm or encephalopathy, despite persistent viremia. Signs of an immunodeficiency syndrome, as evidenced by opportunistic infections and abnormalities in T-cell subpopulations and in in vitro lymphoproliferative responses to mitogens, have not occurred. How—ever, a chimpanzee, inoculated intravenously with whole blood from an HTLV—IIIB infected animal, has, on ‘routine skin testing for tuberculosis, become tuberculin-reactive 23 months postinoculation. Hycobacterium avium- intracellulare was isolated from gastric washings, but no pulmonary or gastrointestinal focus of infection was found. The animal has developed inguinal lymphadenopathy, but is otherwise clinically well. This mycobacterial infection may represent the first indication of an underlying immunodeficiency, and studies to determine the extent of infection are underway. 67 TPan Synergism and Antagonism In Vitro Among Various Antiviral Drugs ' In the Treatment of HIV Infections. *, TING-CHAD CHOU**. KEVAN L. HARTSHORN*, LESLIE A. COIhAN‘k, DAVID A. NEWEYER*, MARTIN S. HIRSCH*, * Massachusetts General Hospital, Harvard Medical School, Boston; **Hemoria1 Sloan Kettering Cancer Center, New York An effective therapy is urgently needed for individuals infected with the Human Immunodeficiency Virus (HIV). Combined therapy with two antiviral drugs that show in vitro or in vivo activity against HIV offer the potential benefits of enhanced antiviral activity, reduced toxicity and prevention of resistance. We thus evaluated various combinations (Table) in vitro utilizing different cell culture systems including peripheral blood lymphocytes, H9 cells and a human monocyte line (3T4). HIV replication was assessed by reverse transcriptase activity, indirect immunofluorescence, p24 capture immunoassay and virus yield. Drug interactions were mathematically evaluated by the median effect principle and the isobologram technique. Mamie] m Phosphonoformate + Recombinant Interferon alpha A Synergy Azidothymidine + Recombinant Interferon alpha A Synergy Azidothymidine + Ribavirin Antagonism Azidothymidine + Lymphoblastoid Interferon Synergy Ribevirin + Phosphonoformate Synergy Ribavirin's antagonism of AZT resulted from phosphorylation inhibition. Other combinations are under study. Drug interactions should be considered when planning clinical trials of anti-HIV combinations. TP31 Regulation of mRNA Accumulation by a Human Inmunodeficiency Virus ' Trans—Activator Protein. DANIEL CAPON, A. JAKOBOVITZ, B. SMITH, M. MUESING, Genentech, Inc., 50. San Francisco, CA, USA HIV LTR-d1rected expression is markedly stimulated in trans by coexpression of a region of the HIV genome encoding a portion of the tat reading frame. Transient expression assay analysis reveals that trans-afii'vat‘lon of LTR-directed expression results primarily from an increase in mRNA accumula- tion. Deletion analysis of the LTR indicates that upstream enhancer elements are dispensible for trans-activation, while sequences 3' of the RNA start site displaying strict orientation and position dependence are required. These sequences, contained in the 5' leader of all HIV transcripts, form a stable stem-loop structure with twofold symetry in the cognate mRNA. Analysis of mutations in the trans—acting region demonstrates that the trans-activator is the protein product of the tat gene. This protein has been identified biochemically in HIV—infected W transfected cells as an Mr 15,000 polypeptide. We discuss possible mechanisms whereby the interaction of plSE with the dyad element promotes the accumulation of LTR-directed mRNA. TP32 Reactivity of HIV and LAV 11 Positive Sera with a Synthetic ' Peptide Antigen in the p34 Nuclease/Integrase Protein. RAYMOND L. HOUGHTON, T. SMITH, K. SHRIVER, J. McCLURE, P.C. SU, and W.L. COSAND, Genetic Systems Corporation, Seattle. WA, USA. A synthetic peptide antigen has been prepared which represents a conserved epitope in the 34kD (Nuclease/Integrase) protein present in HIV. The peptide designated 124 was tested for its reactivity with a panel of 46 sera (35 HIV positive and 11 HIV negative). As compared to the Genetic Systems whole virus assay (LAV-BIA) for detection of antibody to HIV, peptide 124 showed a specificity of 100% and a sensitivity of 97X. Peptide 124 was tested against an additional panel of sera of African origin. Of 61 African sera (28 positive, 25 negative, and 8 atypical by Western Blot), 96.4% (27/28) of positives, 01 (0/25) of negatives and 25% (2/8) of atypicals were positive. In addition, since peptide 124 represents a conserved antigenic epitope amongst AIDS viruses, we analyzed its reactivity with 10 sera that were characterized as positive for core and envelope antigens of LAV II by Western Blot. As expected, 1002 (10/10) reacted in an EIA using LAV II as antigen, 70% (7/10) were positive with our standard LAV—EIA and 80% (8/10) using the single peptide 124 as antigen. These results are consistent with cross-reactions observed between the p34 proteins of HIV and LAV II in Western Blot analysis. In addition, no reactivity of peptide 124 was observed with HTLV I positive sera. These data indicate that peptide 124 will provide an additional tool in peptide based assays for HIV antibody detection. TUESDAY, JUNE 2 TP33 Replicative properties of transsectional and longitudinal HIV iso- ' lates from serum HIV-antigen positive and negative individuals MATHIJS TERSMETTE, R.E.Y. DE GOEDE, J.M.A. LANGE’. J. GOUDSMIT*, J.G. HUISHAN AND F. MIEDEMA, Central Lab. Netherl.Red Cross Blood Transfusion Service, in- corporating the Lab. of Exp. and Clin. Immunol. of the Univ. of Amsterdam. *Dept. of Viral. of the Univ. of Amsterdam, Amsterdam, The Netherlands Virus replication in co-cultures of lymphocytes of seropositive individuals and lymphocytes of healthy blood donors selected for susceptibility to HIV in- fection was quantitated by RT activity and a HIV p24 antigen capture assay. Virus was detected in 1002 of AIDS and ARC patients (n-16), 842 of LAS patients (n-6) and 711 of asymptomatic individuals (n-38). Detection by antigen capture assay was considerably more rapid than by RT assay, especially in asymptomatics (mean: 14.0 vs. 28.1 days). HIV isolates obtained from lymphocytes collected over a two year follow-up period in six persons, showed similar culture charac- teristics within one individual. No clearcut differences were observed between serum HIV antigen—positive and -negative asymptomatic persons. Syncytia were detected in 401 of AIDS/ARC patients, 202 of LAS patients and 201 of asympto— matics. 8/9 Isolates that induced CPE in donor lymphocytes could be transmitted to H9, in contrast to 0/11 non—CPE inducing HIV isolates. One asymptomatic indi- vidual with in-vitro OPE-inducing HIV developed AIDS 16 months after first virus isolation. These data may imply that the probability of developing AIDS may be partly determined by the syncytium inducing capability of the HIV strain present in an infected individual. TP34 Comparisons of antigen detection and virus cultivation ' in HIV-l-infected patients BERND ZORR,K.O.HABERMEHL, Inst.of Clin.and Exper.Virology, Free University of Berlin, Hindenburgdamm 27, 1000 Berlin 45, Germany All of 12 patients selected for an AZT-study gave before onset of treatment a positive HIV-l-result by lymphocyte co- cultivation in tissue culture. Using HIV-l-ELISA for antigen detection (duPont) IO patients were significant reactive, 2 patients with ARC were negative. In HIV-l-infected children the ELISA-antigen-detection is independent from the amount of HIV- neutralizing antibodies. — The antigen ELISA shows a good sensitivity with a detection limit of 20 pg/ml serum. In comparison to a sensitive plaque titration assay on MT 4-cells one ng corresponds to 7xl03 PFU/ml. TP'35 HIV t_at/LTR-mcdiated Expression of Heterologous Genes in Transient Assays 3.9. FERGUSON. L.L. STREHL. L.T. BACHELER. M.M. RAYNER. R. RUGER AND S.R. PE'ITEWAY. E. I. Du Pont de Nemours, Medical Products Department. Wilmington, DE. We have used transient expression assays to study the trans-activation of heterologous genes under the control of the HIV-IIIB LTR. Reporter genes included 15,. M B-galactosidase, chloramphenicol acetyl transferase. and human IL—2. Expression of the reporter gene was monitored in cell lines from several species in the presence and absence of the following viral regulatory genes: HIV t_a_t-III (under SV40 early transcriptional control). human CMV IE-I, pseudorabies virus IE, and human adenovirus-S EIA. HIV ta_t efficiently induced LTR»mediated expression in Hela cells (>400-fold) but was markedly less efficient in each of the nonhuman cell lines tested (2 to 30-fold induction). These results suggest that a major component of tat function is species specific. In HeLa cells expression of the reponer gene unda’ Lat-activated LTR control was 40-fold greater than the level expressed under SV40 early promoter control. CMV IE-I significantly induced HIV LTR expression (~ I0-fold), whereas EIA had no effect on LTR expression. These results suggest that superinfeclion by CMV of a latently HIV108 months) after HIV seroconversion; 3) that AIDS incidence after seroconversion may be slightly higher in homosexual men than in hemophillacs; and 4) that the 1-year morbidity and mortality from pediatric AIDS will be high. TUESDAY, JUNE 2 ":57 Retrospective Case Study of Presuptively Diagnosed AIDS (FDA) in ' New Jersey JG-IN BEIL, E. BISl-BURS, G. WHITAKER, J. MASSEY, J. FRED-l, N.J. State Dept. of Health (NJSDH), 'I‘renton, NJ, T. STARCHER, Centers for Disease anntrol (CDC), Atlanta, GA. Many patients with HIV infection do not meet CDC criteria for AIDS and are not crnrded in AIDS statistics, but they are presumptively diagnosed as having AIDS rrnetheless. The NJSDH, in cooperation with CDC, crnducted a retrospective study of 207 patients randonly chosen fnan the New Jersey registry who were entered into the registry between July 1985 and Jme 1986. All but three of the 207 had engaged in a Imam risk activity. The goalwastodetermimhowmanyofthesepatientsoould, oncloser exaninaticn, be shown to have AIDS. Ten (5%) were diagnosed as meeting CDC criteria for AIDS; another 31 (15%) were PDA on the basis of mysician opinion; and 99 (48%) met NJSDH criteria for ARC. Forty four patients (21% of the sample) had expired by the end of the period studied. of the deceased, only one had been autopsied and met one criteria for AIDS. Another 17 (39% of the deceased) were Judged FDA. while the study suggests that the number of AIDS cases in New Jersey has been undercounted, more conclusive results would depend on more frequent autopsies of deceased FDA and note frequent attanpts to make reliable diagnoses of living FDA. ABSTRACT NOT AVAILABLE AT TIME OF PRINTING TP59 Modeling the Spread of Human Immunodeficiency Virus (HIV) in the United States N. SCOTT CARDELL, D.E. KANOUSE, E.M. GORMAN, C. SERRATO, P.H. REUTER, A.P. WILLIAMS, The RAND Corporation, Santa Monica, CA USA Despite widespread interest in the processes by which HIV infection has spread in various U.S. populations, there have been few attempts to develop mathematical models of the dynamics involved. Yet such models may be extremely useful in predicting the future course of the epidemic for health services planning purposes, identifying the most promising strategies for primary prevention, and estimating the aggregate effects of new medical interventions that are capable of lengthening individual survival. We have developed a computer model of the dynamics of HIV infection that takes into account a broad array of data on the size and sociodemographic composition of various risk groups, estimated seroprevalence rates, the natural history of HIV infection, and patterns of risk-related behavior. The model is fitted to the known history of the AIDS epidemic to date. It reduces our uncertainty abOUt the dynamics of HIV infection and transmission by narrowing the range of possible values that certain important parameters take on. It also allows us to identify which uncertainties in the parameters contribute most to the uncertainties in our forecasts. Results indicate that the future incidence of CDC—defined AIDS is likely to be much higher than accepted U.S. Public Health Service estimates and that a self-sustaining epidemic among heterosexuals in the U.S. is already underway. 72 T260 HIV High-risk lndices among Anti-HIV-negative Blood Donors EVA A. 0PERSKALSKI*, THE TRANSFUSION SAFETY STUDY GROUP* **, *USC School of Medicine, Los Angeles, CA, **other participating institutions. Transfusion Safety Study (T58) is a multifaceted cooperative evaluation of factors influencing risk of transfusion-transmitted HIV infection and progres— sion. As part of TSS, serum samples were stored from persons who were blood donors in September 1984 through January 1985, just prior to routine anti-HIV screening. Data are currently available about high-risk indicea (known AIDS risk factors, hepatitis markers) for 114 anti-HIV(+) and 108 anti-HIV(-) con- trol donors. matched to the former by sex, age, and area of residence. We have determined relative frequencies of high-risk indices in the two groups to assess possible discrepancies between presence of risk factors and anti—HIV status on screening. Among anti-HIV(+) and anti—HIV(—) males, 41% and 12, respectively, were homo- sexual; 422 and OZ were bisexual; and, 101 and 12 were IV drug users. Among anti—HIV(+) and anti-HIV(-) females, 50% and OZ had a known risk factor. The two anti-HIV(—)ma1es with risk factors had a low intensity of exposure. For both sexes, anti-HBc positivity at follow-up 12 to 24 months later was 552 and 12; ALT> 45 was 72 and 5%. In neither sex were there any instances of sero— conversion at follow-up. These data show a high proportion of bisexuals among donor males with homo- sexual contact; these men may be less likely than homosexual males to identify themselves as being in a risk group. The low frequency of high—risk indices among anti-HIV(-) donors with demographic characteristics similar to anti-HIV— (+) donors is reassuring about the sensitivity of present anti-HIV screening. (Supported by Contracts No. NOl—HB—4-7002 and NOI-HB-k—7003 of the National Heart, Lung, and Blood Institute.) “361 Risk Factors for Infection by HIV and Development of AIDS in a ' Cohort of Gay Men. J. ALLEN MCCUTCHAN, D. JACOBSON, C. KENNEDY, S. SPECTOR, M. KLAUBER, D. RICHMAN, et 31., University of California, San Diego, San Diego, CA. To identify factors predictive of either rlsk of infection by human inmuno— deficiency virus (HIV) or subsequent development of AIDS, we performed two case-control comparisons within a longitudinal study of 148 gay men. Eight HIV-seroconverters (SC) were compared to eight seronegatlve controls and 15 HIV-infected men who developed AIDS (DA) after entry were compared to 15 sero- positive men matched for clinical status who did not progress. sc had fewer years of education (14 vs 16), whereas DA had more (16 vs 14). SC were more sexually active, especially in the year before seroconversion. DA were less sexually actlve throughout the period (1981—1984) antedatlng their diag- nosis by 4-6 years. At entry, DA had lower white blood cell counts, hemo- globins, absolute number of CD4+ lymphocytes, total area of reaction to 3 intradermal antigens, serum albumin, and lymphocyte 5’ nucleotidase than controls. IgG (ELISA) to a ZO-amlno acid synthetic peptide (p 62) from the alanine—glycine copolymer region of the Epstein-Barr Virus nuclear antigen (J. Immunol. 134:211, 1985) was lower than controls before and after both seroconverslon and development of AIDS. We conclude that: 1) education and recent sexual behavior is associated with risk of infection, 2) sexual activity is diminished in infected gay men who develop AIDS compared to matched controls who do not, 3) multiple hematological and immunological variables differentiate those infected men at greatest risk of AIDS, and 4) low levels of 196 to an EBNA peptide may predict both increased suscep- tibility to HIV 1nfectlon and development of AIDS. TP62 In Vivo Analysis*of Antiretrovirgl Treatment Strategies in Mice. '*** RUTH M. RUPRECHT , ARLENE SHARPE , RUDOLF*iAENISCH and DAVID *_________________ CHOU , Dana-Egiber Cancer Institute, Boston, MA, Whitehead Institute, Cambridge, MA, Memorial Sloan-Kettering Cancer Center, New York, NY. The reverse transcriptase inhibitor 3'-azido-3'-deoxythymidine (AZT) acts early in the retroviral life cycle, whereas o-interferon reversibly inhibits late events during retroviral propagation. AZT suppresses Rauscher murine leukemia virus complex (RLV)-induced disease in adult BALE/c mice. Longterm AZT treatment, however, leads to severe bone marrow depression. Recombinant human interferon c-A/D (rHuIFNo-A/D) strongly inhibits RLV—induced splenomega- ly in BALB/c mice. Combining suboptimal doses of AZT and rHuIFNo-A/D leads to virtually complete suppression of splenomegaly without hematological toxicity. We conclude that AZT and rHuIFNa-A/D are highly synergistic i3 vivo. We have also developed murine models to study retroviral neurovirulence, as well as 12 utero and perinatal infection, by infecting SWR/J mice as midgesta~ tion embryos or neonates with Cas-Br-E virus which causes hind limb paralysis. AZT given orally to pregnant and/or lactating females delayed the onset of paralysis and prolonged life of infected mice in a dose~dependent fashion. conclude: 1) AZT is active in the CNS sanctuary, 2) AZT is effective across the placental barrier, 3) AZT is secreted into milk, and 4) pre- or perinatal infection and therapy can be evaluated in our model system. The significance of our studies lies in the rapid and cost-effective ways in which questions relevant to human neurovirulent retroviruses can be studied ifl vivo. Sup- ported by a contract from the Commonwealth of Massachusetts Department of Public Health (RMR), a Faculty Development Award from the Pharmaceutical Manufacturers Association Foundation (RMR) and a Lucille P. Markey Charitable Trust Scholarship (AS). AZT was a gift from the Burroughs Wellcome Co., and rHuIFNo-A/D from Hoffmann La Roche, Inc. We TUE DAY, JUNE 2 EVALUATION of a NEW VIRONOSTIKA HIV CONFIRMATION ASSAY GABY VERCAUTEREN*, W KEUR*, G VAN DER GROEN*, P PIOT* *Institute of Tropical Medicine, Antwerp, Belgium TP. 63 In the Organon anti-HIV confirmation assay (CA) wells of Vironstika anti— HTLV III enzyme immunoassay strips (EIA) are preincubated overnight, respecti— vely with blocking sheep anti—HIV serum, sheep anti—H9 serum and normal sheep serum. Thus HIV antibodies from a truly positive specimen can no longer bind to the HIV antigen. This blocking effect is compared with that of the anti— H9 serum. If the ratio of the optical density in the presence of the anti—H9 serum versus the reaction with the anti-HIV blocking serum is greater then 2.0. the sample isconsidered positive. A ratio between 1.5 and 2.0 is inter— preted as doubtful or "gray zone" value. In this preliminary study 180 sera were tested in the EIA, CA and in two additional confirmation assays, indirect immunofluorescence assay (IFA) and immunoblot assay (IBA). The EIA results showed an overall concordance of 90.9 X with the CA. The CA revealed 4.3 Z (4/94) false positive EIA results. These 4 negative CA results were confirmed by IFA and IBA. Concordance of the CA with IFA and IBA was 91.5 Z and 94.5 Z respectively. Two sera were negative in the CA, but positive in the IBA. One of them was also positive in the EIA and IFA and the other one was negative in EIA and IFA. Three sera (3.1 Z) positive in EIA and CA could not be confirmed by IFA nor with IBA. All "gray zone" CA results were negative in IFA and IBA. An advantage of the CA is the use of the Vironostika anti—HTLV III EIA strips. This CA may be useful to confirm the positive result of a single performed EIA. TES‘ Clinical and Behavioral Predictors of Developing AIDS and Related Outcomes among Asymptomatic HIV Seropositive Homosexual Men in Boston KENNETH MAYER", J. MCCUSKER**, A.M. STODDARD**, S.P. SALTZMAN*, M.W. HOONT, J.E. GROOPMAN*, et al, Fenway Community Health Center, Boston and University of Massachusetts, Amherst, MA, USA. Seventy four of 290 asymptomatic (AS) gay men enrolled in a pro- spective study of the natural history of HIV infection between 1/85-5/86 were Ab(+) (25.5%). of 57 followed for more than a year (3 1 visit every 6 months), only 12 have remained AS, whereas 35 developed persistent generalized lymphadenopathy (PGL), 9 thrush (2 with PGL), and 4 zoster. All 4 of the men who developed AIDS, had thrush first, whereas none of the men with zoster + AIDS; only 1 had prior PGL. Lifetime number of sexual partners, number of partners in the preceding 6 months, frequency of receptive ano- genital exposure to semen, number of anogenital partners, drug use history and prior sexually transmitted disease history were not significantly different between men who remained AS and those with AIDS-related clinical outcomes. Whereas the polymorphonuclear cell count and hematocrit did not differ on the initial exam between those who stayed AS and those who got sicker, the mean number of lymphocytes was significantly different (p=.006) between the AS men (2250), those who developed PGL (1722) and those who + thrush, zoster or AIDS (1499). Thus, behavioral risk factors associated with becoming infected with HIV are not predictive of the develop- ment of PGL, thrush, zoster or AIDS; but thrush and lymphopenia are associated with early clinical progression towards worse out- comes. TP65 Prevalence and Incidence of AIDS, ARC and HIV Infection in a Gay NYC ' Cohort. JOHN L. MARTIN, Columbia U. School of Public Health,NYC,NY. Prevalence and incidence rates of AIDS, ARC, and HIV infection (antibody) were calculated from data collected on a cohort of 745 NYC gay men. The AIDS- free sample was recruited and interviewed in mid-1985 in order to examine soc- ial and behavioral risk factors for AIDS and the presence of signs of ARC. An annual follow-up interview was completed one year later. Fourty—seven percent of the sample (N=357) underwent an initial serologic evaluation for HIV anti- body in early 1986 and a follow-up blood sample was obtained six months later, at the time of the follow-up interview. Prevalence of HIV antibody in early 1986 was 34%. Including the group of men with a history of sharing a needle for IV drug use increases this value to 36%. The six month incidence of setoconversion was two out of 230 seronegatives. Pro-rated for 12 months this represents an annual rate of 17.4 new infections per 1,000 susceptible gay men. The prevalence of pre—AIDS conditions or symptoms of ARC [thrush,herpes zos- ter, lymphadenopathy, unexplained weight loss of 10 lbs (+), persistent unex- plained fevers of 100°F (+), persistent unexplained diarrhea] during the 1984— 85 year was 21% for the total sample and 38% for HIV antibody positive men. Incidence of new cases of ARC has not yet been calculated. During the course of the one year follow-up interval, 18 incident cases of AIDS occurred. For the total sample this represents a rate of 24 new AIDS cases per 1,000 gay men. Using only HIV antibody positive men for the denomin- ator, the annual incidence of AIDS is 67 per 1,000 HIV infected gay men. The low seroconversion rate relative to the high AIDS incidence rate indica- tes that the rate of increase of new AIDS cases among gay men should decline in future years if sexual activity remains low or continues to decline at the rate we have previously reported. 73 TP66 A Method for Estimating HIV Seroprevalence Rates in Urban Areas ' with High Rates of I.V. Drug Abuse: The Case of the Bronx ERNEST DRUCKER, S.H. VERMUND, Department of Epidemiology & Social Medicine, Montefiore Medical Center/Albert Einstein College of Medicine, Bronx, NY, USA In the absence of large scale seroprevalence surveys it is still possible, using available data, to estimate the probable magnitude and geographic localization of the AIDS epidemic in urban area with high rates of intravenous drug abuse (IVDA). The Bronx with 1.16 million people has a distinctive pattern of prevalence and distribution of AIDS, i.e., 69% of AIDS cases are among IVDA's, 20% are female, 89% are Black and Hispanic, and 4.5% are children. Local data on AIDS cases (by risk factors, age & sex) can be combined with local indices of the IVDA population, e.g., drug—related deaths and N.Y. State drug treatment data, to estimate numbers of IVDA's and rates of HIV seroprevalence. In this application of the model, HIV seroprevalence is calculated for: Bronx males & females age 25—44, a group comprising 76% of all Bronx AIDS cases through November 1986; and for the South Bronx area where AIDS cases are most concentrated. Overall, the Bronx is estimated to have between 31,300 and 46,200 IVDA‘s of whom 78% fall into the 25-44 age group. 30%—50% of female IVDA's and 4095—6025 of male IVDA's are considered to be HIV positive based on local sero-surveys. These figures produce a seroprevalence range of 5.3%—ll.8% for all Bronx males age 25—44 and 1.12—2.61; for females. For the South Bronx, with 66% of all IVDA's and 38% of the population, these rates are 9.3%—20.6% for males age 25—44, and LBS-4.3% for females. These must be considered minimum estimates of Bronx seroprevalence in this age group as they do not take into account the contribution of risk groups other than IVDA's. Implications for heterosexual and vertical transmission are discussed. TP67 Additional Evidence for Lack of Transmission of HIV Infection to ' Ibusehold (bntacts of AIDS Patients. GH FRIHDLAND,* B SALTZMAN,* M WEEKS/”I P KAHL,‘ C FEINER,* M MAYERS, et a1. hTmtefiore Medical Center/Albert Einstein 0011. of Med., Bx. NY,**CDC,Atlanta, Ga, USA. We report on the continuing enrollment and evaluation of non—sexpal household contacts of adult AIDS patients (pts.). 200 contacts of 85 AIDS pts. were evaluated with detailed interviews, physical exams, and antibodies to HIV; 99 contacts were re—evaluated 6—12 months after cessation of household contact or death of the pt. Mean age of contacts 10.4 years: 57 mder 6, 1132 6—19, 4l>19 years. Median duration of hoteehold contact from 18 months prior to symptoms in pts. to last contact, 2.1 months. Median time elapsed from first contact dm‘ing this period to last evaluation 35 months. No homebold oontact has AIDS. 199/30 are negative for serum antibody to HIV. the HIV-I» biologic child of a woman with AIDS likely acquired infection perinatally. Sharing of selected household facilities, items and personal interactim. with AIDS patient anxxwg 199 household menters: Shared Activi % Sharin s Shared (Median) Da Shared (Cumulative) ‘Wfl flm— i tellet, bath, kitchen 105, 793-II36,§57 oonb 69 397 46,777 bowels 48 418 36,937 utensils 38 108 16,402 plates 51 71 17,044 glasses 55 84 23,984 hugging 76 352 55, 3% kiss ' 78 352 55 , 728 This study slows that household members remain at minimal to no risk for HIV transmission (95% coo-1.49) despite [xolmged and substantial close non-sexual contact with AIIS patients, and after reevaluation 6-12 months after contact ceased. 11358 Western Blot-positive and -negatIVe Sera from Harare, Zimbabwe and ' New York, NV, USA are identified Equally by a Synthetic Polypeptide- based Enzyme-linked Immunoassay (ELISA) FREDERICK P. SIEGAL*, C.Y. VANG**, T. HONG**, K. SHAH*, D. IMPERATO*, J.C. EMMANUEL***, *Long Island Jewlsh Medical Center (LIJMC), New Hyde Park, NY, **Unlted Biomedical Inc. (UBI), Lake Success, NY. USA and ***The Blood Transfusion Service, Harare, Zimbabwe. Sera from 499 subjects seen at our institutions (434 from NY, 65 from Harare) were blindly assayed for reactlvity with a new ELISA for HIV antibodies. The antigenic adsorbent for this system Is a mixture of synthetic polypeptides representing highly antigenic epitopes of HIV gp41 and p25. Sera were selected on clinical grounds and/or known prior reactlvlty with currently employed ELISA techniques; 324 represented a wide spectrum of HIV infection (duration and clinical stage), I75 were controls. The control sera represented normal laboratory workers, parenterally and sexually exposed people, several primary lmmunodeflciencies, autoinmune diseases, thymoma, classical Kaposi's sarcoma, T and B non-Hodgkin's lymphomas and Hodgkin's disease. Most sera were assayed independently at both UBI and LIJMC and all ELISA results were compared with results from "Western" blots (us). There were no false negatives, including 5 sera having no detectable band corresponding to gp4l, one of which (AIDS-0|) also lacked all reactivity on HB. There were also no false posltlve results. These data suggest that despite virus heterogeneity related to geographic distances, the epitopes in question remain Invarlate, and the assay Is consistently highly sensitive. TUESDAY, JUNE 2 TP 59 Prevalence and Persistence of HN Antigen among IV Drug Users. ' W2 SR FRIEDMAN", J-P ALLAIN'". D MILDVAN'“'. M LEUTHER'", M MARMOR""', S BEATRICE""" et al. 'NYS Div. of Substance Abuse," NDFI. Inc., "' Abbott Labs, "" Beth Israel Med. Can, ""' NYU Med. Cen., """ NYC Dept. Health, New York NY Recently developed tests for detecting HIV antigen in serum provide a means for examining the role of serum antigen In the natural history of HIV infection. We examined the prevalence. persistence and sequelae of detectable HIV antigen In a cohort oi 138 intravenous dmg users in New York City. No subject had AIDS or ARC at the beginning of the study; each subject was seen twice with a mean 019 months between the two data collection points. HIV antigen was assessed with me Abbott test. antibody was assessed with Abbott ELISA and Western blot tests. Antigen was detected In 5/66 (8%) of the subjects who were initially antibody positive. in 0/4 of subjects who became antibody positive during the follow-up period. and In use (1 5%) of the subjects who were antibody negative at both the start and end of tollow-up. All subjects who were antigen positive at the start oi follow-up were also antigen positive at the end 01 the period; one antibody positive subject developed antigen during the period. Antibody to gp41 was more common than antibody to p24 in antigen positive subjects. Antigen was associated with increased rates of T4. T8 and B cell loss. 2/5 antigen positive, antibody positive subjects have since developed AIDS or died with ARC. compared to 3 of 61 antigen negative. antibody positive subjects (p < .05). (Disease incidence will be updated to the time of the conference). Repeated ELISA antibody tests of the for one antigen positive subject were negative at both time points; repeated Westem blots for this subject showed no antibody to p24. gp41 or gp120 at either time (additional testing is being conducted). This was the only subject for whom HIV antigen level declined. Presence of HIV antigen In serum of IV drug users at risk tor AIDS appears to be infrequent, relatively stable over time. and a potential marker for development 01 clinical disease. Further relationships among antigen presence. presence of specific HIV antibody. and other potential markers of disease progression will be presented. TP70 Factors Influencing the Risk of Infection with Human Imunodeficiency Virus in a ' Cohort of Homosexual Men - Denver 1983-1955 QRNELIS hm RImIJER, ILA. PM, ILL. COHN, C.R. HORSBU‘RGH, A..I. DAVIDSON and F.N. JUDSON, Denver Disease Control Service and The University of Colorado, Denver 00. He studied factors associated with infection with the human imunodeficiency virus (HIV) in a cohort of 231 gay men enrolled from Itovember 1982 through May 1985, including A0 asymptomatic HIV antibody negative (AS-), 21 asymptomatic antibody positive (AS+), 7A with generalized lymphsdeno- pathy (GLS), 39 with AIDSrrelated complex (ARC) and 57 with AIDS. Because univariate analysis did not show significant differences between AS+ and 61.5 or between ARC and AIDS, these groups were combined for analysis. Riskfactors in AS- AS+/GLS ARC/AIDS Ugivargte fllygis W t I. months “#0 95 "=9 96 N=96 96 1’" W P” ds i0 1. Erratus 3 (7.5) 1.9 (51.5) 32 (33.3) (0.00001 (0.005 (0.0001 15.1» (Ml-58.3) Receptive anal)30 1 (2.5) 21» (25.2) 12 (12.5) (0.005 NS (0.05 No.6 (1 7‘126.0) ARC/AIDS contact 3 (7.5) 25 (25.2) 13 (13.5) (0.05 NS <0.005 8.8 (2 2-35.3) Sex partners>20 1 (2.5) 17 (17.8) 08 (08.3) (0.05 NS 0.062 3 1 (0 845.1) IV drug use 2 (5.0) 19 (20.0) 21 (21.8) (0.05 (0.05 0.063 5 0 (0 9-27.5) Insertive anal>§0 2 (5.0) 03 (1.5.1) 21 (21.8) (0.05 N§ *AS- vs + GLS- i“(AS‘ vs ARC I S- M 5+ S C.1.=Conf dence inte In mitivariate analysis (table) the use of enemas, number of episodes of receptive anal inter- course and sexual contact with someone with AIDS or AIDS related conditions were all indepen' dently associated with HIV infection. IV drug use and number of sexual partners improved the mltivariste model but did not reach statistical significance. In univariste analysis the ARC/AIDS group did not differ significantly from A5- as to number of episodes of receptive or insertive anal intercourse and number of sexual partners, but: this most likely represents confounding that occurs when current risk factor behavior in fatally ill men is used in place of risk factor behavior at the time of HIV transmission. It indicates however that this group has become less sexually active and that HIV infection is largely spread by relatively healthy infected men. TP.71 DAVID L. com, A.J. mvmsul, ILA. m, F.1I. JUN, Denver Disease Control Servim (115), University of Colorado lbalth Sciences (hitter, Miller, 0), U.S.A. AltlnghthszeravebemoverwfimcasesofAUSreportedlntlelm, therehavebeensua- prisirgly few mrehensive analyses of mmlity in A113 patients (pts). In 1985 [X28 inple- named the capiterized AIDS Reporting systan (ARS), which utilizes mas software program provided by the Carters for Disease (kmtml (ma). lehy, 1982 thrush became: 31, 1986, 119 adult cases of GD-deflrai Am were reported, of vim 202(651) had died. Follow-up unr- btxlity and nomlity infatuation was ascertained on 30k (98%). 'lhoee wlnee survival was not ascertained were censored as of the last Magnetic entry in the ARS. thdiansmvival (t6) fmntineofdiegmaisofallptsmsmdays (d), ofptewho initially presented with Ramayana Ma (PC, rr-IBZ) 257 d, inapoai’s sarcoma (KS, n-65) 293 d, PC am KS (mlo) 223 d, otter opportunistic diseases (CI), 11-52) 140 d, aid PC who survived at least 60 d after disgusts (II-115) 337 d. is by craraniseim category was for gsym(n-221) 250d, gaymenard WNW-48) 236d, heteroeaonlatd IVIJJ(n-13) 251d, lamphiliace (m7) 6% d, letemeexual cantacte (rt-5) 293 d, tramfusion recipients (m5) 320 d, and no idmtified risk (Nl‘R, (FIG) 87 d. is for pts with lynphom at any tine (11-26) was 137 d carpeted wlth no lywlmra (rt-283) 260 d; ml for diseasimced cytmegalovirue (W, 11-50) 198 d and no 0” (tr-259) 255 d. is for pts with or wltl'out: Wane her-pa, M. avirm-irrtrecellulare, Cmfiida esophagus, u'yptoeporldjceis, and cryptoooccoeis was not significantly different. Ptsvtopresentwithmluveaworseprognoeis t-hanltSand/orPC,andPCptswlneurv1ve trell- initial episode have tl'e beet prognosis. NIR pts have a mfleantly worse programs than other Mimi categories, probably became diagnoses are delayed. Lynplm and 0N indicate a worse progmeie, although (Ml may be mdendiagmeed. ABS ls meful for followlrg prognosis in differed: types of AIDS pts, and for mnitorirg trends over time. Mortality in ADS in (blorado: Life-Table Analysis from tin AIDS Feportizg System 74 "”2 REVERSIBILITV AND PROGRESSIDN 0F PERSISTING AIDS-RELATED COMPLEX BARBARA VISSCHER, R DETELS, J PHAIR, C RlNALDO, R KASLOH, R FOX. u t center Cohort Study, NIAID, Bethesda, MD. A cohort of 693 HIV antibody positive homosexual men in Los Angeles were characterized as being asymptomatic (well), having persistent generalized lymphadenopathy (PGL) or AIDS Related Complex (ARC) on two separate visits at least 6 months apart and were re-examlned 6-12 months later. ARC was defined as one or more of the following reported conditions: fever or diar- rhea lasting more than two weeks or involuntary weight loss greater than 9 pounds. Men were considered to have PGL if examination revealed non-conti— guous lymph nodes greater than 1 cm In diameter at 2 or more non-inguinal sites. Men who had been in that same status at the subsequent consecutive visits were most likely to remain in that same status at the subsequent visit. The AIDS attach rate was highest for those with a diagnosis of ARC on two consecutive visits (12%) but was lower and similar (4—7%) among the other groups PGL/PGL, well/well, ARC/PGL, PGL/ARC. The ARC attack rates were similar and lower for those with any sequential status other than ARC/ARC. These observations suggest that persisting ARC is an unfavorable prognostic sign, although at least some men with persisting ARC do revert to either PGL or well, at least temporarily. PGL alone does not appear to be an unfavorable prognostic sign over the time span studied. For the meeting, we will have data from an additional 1000 seropositive men in Baltimore, Chicago and Pittsburgh. TP_73 Predictors of The Hazard of AIDS Among HIV Seropositive Gay Men. B.FRANK POLK, A.MUNOZ, R.FOX, R.KASLON, J.PHAIR, C.RINALDO, R.DETELS, for the Multicenter AIDS Cohort Study (MACS), NIH, Bethesda, MD. Of 4,955 gay men who enrolled in a prospective stud , 1828 were seropositive for HIV at entry. Among the seropositives, 164 (9.0%) developed AIDS during 24 months of follow-up. Exposure variables of interest, with data collected at entry and at three subsequent six-monthly visits, included age, race, adi- posity, sexual activity, CBC, T—cell subsets, serum inmunoglobulins, serum antibody to CMV and HIV, serum HbsAg, and AIDS-related complex (ARC). Follow- up data were available on 1820, 1614, 1454 and 1332 participants at the four respective visits. We conducted a stratified analysis using a proportional hazards regression model. In an attempt to control for the unknown time since infection, the strata were defined by the entry CD4 number (a known marker of disease progression) and the rate of change in the number of CD4 cells. The estimates of the relative hazards from the multivariate analysis for those variables that made independent significant contributions to the final model were: KS 01 Age 1.51 for 10 yrs. 179 1750 log CDB 2.10 for twice 1.89 2.18 log igA 1.37 for twice 1.54 1.38 Hemoglobin 1.20 for -1 gm% 1.19 (NS) 1.26 HIV antibody 1.79 for -1 0.0. 1.19 (NS) 2.02 and opportunistic infection (OI) were analyzed When Kaposi's sarcoma KS) ' . . separately, the hazard 0 K was more strongly assoctated WIth older age .while the hazard of 01 was more strongly assoctated with increased number of C08 cells and decreased level of H1 antibody. In Sumner , after adJusting for number at entry and change in CD4 cell number, severe other variables have predictive information regarding the development of AIDS. TP14 ClJnical Significance of Anti-HIV Antibodies in Asynptamtic Blood Donors: A Prospective Study. HARVEYJ- ALTER', S.I.-". LEW. 11.6. ram, J.J. WEI“, F. BARR“, J.L. POW, et a]... fiiflm Carter, NIH, “finality-ton Region Red Cross. 88aeynptaraticlrhetemblot+ (WB+)blooddcrmarr151 KIM, HB-cmtrol dornrshave thus farbeenatrolled inaSHyesrprospective study. thwarted withtheWB—cmtmle, wad-imividtnlewerenm‘e frequentlynnle (BBSVBSQ!) andblad: (51%vs60). 'lheprobableewrceofl-IIVexpoeurewaslnmeml wit-act, 75%; heterosexual met, 17%; IV drugs, 1%; micron. 78. Nate were transfusim related. on initial evaluation of “3+ subjects: 1) 38% had extra- i.ngu:l.nal lyrrriiadencpethy; 2) neon T4 cell mmber was 450 (range 120 to 982) an! mean T4/T3 ratio was 0.75 (range 0.26 to 1.7); 3) 47% had dhninished in vitm reepmseetotetarmarflZSShaddecreasedrespcnaestoPHAand/orfiflr 4) 45% had Iw > 1&0 rig/dL: an! 5) 2% had platelets < 100.000/u1. HIV was isolated from mly 8 of 88 (90) cultured at Biotedt and 7 of 74 (10!) untured at (1!). This is markedly lower than earlier (Ix: studies (57% viral isolatim) and sug- gesteachengeintheconstituencyofthewdcrmpcpflatlm, asalsoinplied by questions relating to lifestyle. On initial visit, 55 (62%) were (DC group II and 33 (388) cpc group III. mugs-18mm follow-«p, cnedcrorprogreesedtogroupNAmdcneto gmup IV C—l (gamut-.15). In these patlmta, the interval franmllnatt to disease was 16 and 12 nmths. respectively. T4 cell tuber and in vitro innune menses eluted progressive deterioratim in these on individuals, arflviruemisolatedjustpriortomtofclinicaldisease. NateoffltsEIA+,HB—cmtroldanrsweminlumntflvdak had evidence of HIV-related disease. :Inllune inpeitmnt, or positive viral cul- tures. We believe these represent false positive reactions and mmt mirr- statumtoflmdtdamintpthedampcol. andnme TUESDAY, JUNE 2 TP75 Heterosexual Transmission of AIDS in llew York city ' MAR! All CHIASSOI, R. SIOIEBUENIE, A. LEKATSAS, J. WALKER. new York city Department of Health, lY, IY. Although heterosexual transmission of HIV is reported to be the most common mode of transmission in Central Africa and Haiti, the extent to which this virus will spread among heterosexuals in the USA is unknown. We examined lew York city Dept. of Health (HYCDOH) and national surveillance data to evaluate the patterns of heterosexual risk behavior among AIDS cases. The 8681 cases reported in IYC through 1986 account for 301 of the total us cases. Approximately 2% of both NYC and total us cases occur among heterosexual partners of risk group members (HYCDOH classifies persons from Haiti/Central Africa separately). Through 1986, 182 sex partner cases were reported in NYC; 3 rules and 179 females. All female partners of the male cases were IVDUs. Risks of the rule partners of the female cases were as follows: 153 (85%) IVDus; 20 (111) bisexual; 3 (2%) Haitian or Central African; 2 (1%) bisexual IVDUs; 1 (1%) hemophiliac. In IYC sex partner cases have remained at about 2% of the total cases since 1982. Infected heterosexual IVDUs comprise the major reservoir of HIV for the heterosexual population. while the 2570 cases among heterosexual IVDUs in NYC account for 531 of US IVDU cases, HYC sex partner cases account for only 36% of the sex partner cases: male cases are 3.51 and female cases 42% of the 509 us sex partner cases. Differences between NYC and US data may be due to better risk identification through more thorough case investigation by HYCDOH. NYC surveillance data suggest that heterosexual transmission does occur and females appear to be at greater risk than males. To avoid further heterosexual transmission in HYC, effective prevention strategies should include a broadly based education program, but focus on the major source of HIV in the heterosexual community, infected IVDUs. TP76 survival Analysis of children Reported with AIDS in law York ' City, 1982-1986. PAULIII A. THOMAS, H. I. O'DOHIBLL, L. LBSSIBR, New York city Department of Health, New York, HY. The incidence of Acquired Inmunodeficiency Syndrome (AIDS) in children under age 13 continues to increase in low York city (ch), but the course of illness and prognosis remains incompletely described. One—hundred forty seven children have been reported with maternally transmitted AIDS from 1982 through 1986. Hedian age at onset of symptoms of immunodeficiency was five months and at diagnosis of first opportunistic infection was 11 months. Survival analysis was performed on the 11‘ with either Pneumocyatia carinii pneumonia (PCP) or Lymphocytic Interstitial Pneumonitis (LIP). for 87 children with PCP, median survival from birth was 14 months (Interquartile (IQ) range-29 nu.). Hedian survival was longer for 42 females than for ‘5 males (19 vs 11 mo.). Hispanic males had the poorest median survival, at six months for 15 with PCP (IQ range-I9 mo.). Hedian survival for 26 children with LIP who never had PCP is strikingly different at 91 months. numbers of cases in different racial and diagnostic groups are too small to be compared statistically. Seven children, aged four to nine years have survived three or more years beyond initial diagnosis. PCP as primary diagnosis was present in one, LIP in five, and both diagnoses in one. These data confirm the very different course of HIV-infected children who present with LIP vs. PCP. Differences in therapy must be examined in future survival analyses. TE77 Fatal Unconfirmed Cases of AIDS Chi-BEE E_ _H.A._LEV_. 5 HDRNITZ. v REFF. K HERNDON. Dallas County Health Department. Dallas, Tx The current AIDS surveillance definition underestimates the magnitude of mortality associated with AIDS and the widespread availability of HIVab testing after June, 1985 has added a new dimension that permits an examination of HIV associated mortality. Reports were obtained from physicians, infection control practi— tioners, and other sources including review of all death certificates. Suspects were investigated by a nurse epidemiol— ogist. From 1981-86, 474 Dallas residents were reported as having AIDS, of whom 281 (59.3%) had died by December El, 1986. An additional 371 persons were reported by physicians and other sources as possible cases of whom “E (11.9%) died before December 31, 1986. Two died of suicide (1 was known HIV positive). Another 34 were known to be HIV positive: 15 did not meet the criteria for the AIDS surveillance definition (4 were transplant recipients, 3 had received steroid therapy for non-malignant conditions, 4 had disseminated infections [1 TB, 3 coccidiodomycosis], and 4 had lyhphomas or leukemias). Another 19 died of illnesses suggestive of AIDS, but confirmatory diagnostic tests were lacking: 6 persons underwent diagnostic procedures, not resulting in diagnosis, and 13 had no diagnostic procedure; none had a post-marten. The pro- portion of deaths possibly attributable to HIV are underestimated by 6% to 10% due to lack of diagnostic procedures and post-mortem examinations. In the future physicians may be less aggressive in AIDS diagnosis, resulting in greater underestimation; of HIV mortality. In Dallas, Texas. 75 TP78 HIV Sero-Survey of Post-Patton Women at a Municipal Hosptial ' in New York City. S. LANDESMAN,‘ SUSAN HOLMAN‘, S. MCCALLA‘, 0. SIJIN', J. WEBER“, El. MINNOFP’, ,SUNY Health Science Center at Brooklyn, Brooklyn, N.Y. We performed a sore—survey of all new mothers admitted to the obstetrical service of a municipal hospital serving the urban poor. Cord blood was used for HIV testing; all women, on the day after delivery were interviewed for HIV related risk factors. Blood samples and questionnaires were given a code number and personal identifiers were destroyed prior to testing. six hundred women delivered: complete data is available on 527. The remaining delivered on weekends or were discharged before interview. one hundred twenty-three of 527 women(23\) had a self reported risk factor; 404 (773) had no known risk factors. All samples were tested by ELISA and confirmed by Western Blot ("3). Women with risk factors had a WB done even if the ELISA was negative. Thirteen samples, 2.451 (1.4-4.3,1 95% C.I.), were Western Blot postive (WB+); ll of which were also ELISA positive. Eight positive samples were in persons with risk factors (3 IVDA, l Haitian, 1 multiple sex partners 1 transfusion, 2 with a sex Thus 8/123(6.5\) of women with a risk factor (1.2!) samples from non-risk group women partner who used drugs). were positive. Five of 404 were positive. Taking an appropriate medical history concerning risk factors for the purpose of HIV counselling and testing during early pregnancy will only identify 61a of the infected population at our institution. Testing of the entire prenatal population at our hospital would be required for identification of the remaining 39‘ of seropositive women. T279 MALNUTRITION AND HIV ANTIBODY PREVALENCE IN THE CENTRAL AFRICAN REPUBLIC. Jean P. GONZALEZ*, 5. 3mm “cams“, GEORGES-counnor*** and A.J. croacas***, *Instltut Scientifique pour le Développement en Coopération, République Centrafricaine (RCA), *Centre de Diététique Boasangoa, RCA, ***Inst1tut Pasteur de Bangui, RCA. HIV antibody prevalence has been studied simultaneously in mothers and their malnourished children, in a rural area of the Central African Repu- blic (CAR). Children were selected on the basis of their nutritional status 1.e. moderate protein energy malnutrition (P E M), kwashiorkor or marasmus. The results obtained from rural area have been compared to those previously obtained in an urban pediatric population as well as those recorded in the general population of the CAR. Elisa was used for sets screening, while Western Blot allowed us to con- firm the presence of anti HIV 1 antibodies when reacting with either GPllO, GPAl or both. Anti HIV 1 as well as HIV 2 antibodies are absent in the healthy control group of children of less than 15 years, while they are found in 12.3% of the malnourished children of the urban area as compared to 3.91 in the rural area. c.c. MATH10T***, M.c. Francois de Recherche ORSTOM, Bangui, Expérimentale de These differences do not seem to be due only to environmental factors but more likely to the way of life of the mothers of sick children under investigation. T980 Western-blot in HIV seroconversion the importance of detecting anti go I l0ll20, the earliest envelope antibodies. L. HOE]. and the RI'I‘ROYIRUS GROUP OF THE FRDICH SOCIETY OF BLOOD TRANSFUSION - Paris, France We present a Western—blot (w-b) study of anti-HIV antibodies in sequential sera collected Iron 25 individuals at the tile of seroconversion and beyond. V-bs were carried out with couercially available kit: tron BIO'I’ECII—DUPOHI‘, BIORAD and DIAGNOSTIC PAS‘l‘EUR. The strips loads in gp 110/120 and 913 11 antigens were systenticolly controlled. In 6 cases seroconversion was proved by the discovery of a positive whole virus anti—HIV ELISA less than one month after a previous negative test. In 19 cases the incomplete pattern observed in w-b on the first positive soaple was suggestive of early seroconversion and indeed siaultaneous study with seaples collected later demonstrated the completion to a typical positive anti-HIV w-b pattern, 0n the first positive sanples the antibodies observed were only : anti—p 25 (with the strongest signal), faint anti—p18 and 1355 am anti- p110/120. Anti p 41 were never detected at this early stage but appeared on soaples collected 3 weeks to as long as 3 south: later . Considering existing cross—reaction with gay gene products in w-b, the criterion of anti HIV specificity relies on the detection of antibodies directed against an em'gene product. is eaphasize the iaportence of using v—b filters rich in gp 110/120 in confirmatory tests to allow for an earlier diagnosis and a better discrisinetion between true positives and non HIV specific reactions. TUESDAY, JUNE 2 TP81 Neutralizing Antibodies against HIV in Relation to AIDS related ' Diseases. MAIKEN ARENDRUP*, K. Ulrich*, J.0. Nielsen**, 3.0. Lindhardt*, C. Pedersen** K. Krogsgaard**. *Lab. of Tumor Virology, The Fibiger Institute, **Dept of In- fectious Diseases, Hvidovre Hospital. Copenhagen, Denmark. Seventy consecutive frozen serum samples collected over a 1—5% year period from 10 HIV (Human Immunodeficiency Virus) antibody positive individuals were tested in a microplate ID assay for neutralizing antibodies (NA) against a Da— nish HIV isolate and the results related to disease outcome. Virusproduction was monitored by a microplate reverse transcriptase assay. Total anti HIV was titrated in ELISA and antibodies against core and envelope proteins detected by Abbott's HTLV—III confirmatory assay. One patient reached stable titers of NA > 1:640 % year after seroconversion, and 3 patients around 1:100 after 2 years. One patient had titers < 1:100, and 5 patients permanently titers between 1:10 and 1:20. The 4 patients with titers > 1:100 remained healthy during the entire observation period (2%— % years). One of the 6 patients with titers < 1:100 developed AIDS, one Hodgkins Lymphoma (HL), one ARC, and 3 remained healthy. The titer of total anti HIV varied between 1:740 and 1290000 and correlated to the titer of NA. The titerratio (IDg /ELISA titer) varied appr. a 100 fold indicating the neutralizing capacity is probably a function of quality as well as quantity of the antibodies. In all serum samples antibodies against envelope proteins were detected. Two patients lacked antibodies against core proteins (CPA) (1 AIDS, 1 HL, ID O 1:100 in this study remained healthy during the entire observation period. 113.82 CLUSTER DF HETERUSEXUAL TRANSMISSION OF HIV IN BRUSSELS. N.CLUMECK, P. HERMANS, H. TAELMAN, D. RUTH, E. 213515, 5. DE HIT (St Pierre University Hospital, Brussels and Institute of Tropical Medicine, Antwerp, Belgium). A 48y. old single central African engineer was found to have ARC in 1985. He died in July 1986 with HIV encephalitis and pneumonia. He lived in Belgium since 1965, travelled regularly to Central Africa and had no history of homo— sexuality, IV drug use, or blood transfusion. Contact tracing allowed identi— fication of 19 women (12 middle—class Europeans, 7 Africans; mean age: 35y.) who had had sexual contacts (only vaginal) with the index case in Brussels during the last 7 years. 8/19 women were married and mean number of children was 1.7 (range 0-4). Number and duration of sexual contacts with the index ca— se ranged from one to multiple contacts during two years or more. 17/19 women have been examined and 10 of them (59%) (7 Europeans, 3 Africans) had antibo— dies against HIV (demonstrated by ELISA and Western blot). The index case was the only potential source of infection for the white women for whom no sexual promiscuity (less than 3 partners/y.), no travel to Africa, no sexual contact with other men belonging to high risk groups for HIV, no IV drug use and no transfusion was found. 7/10 seropositive women described mononucleosis-like symptoms of acute HIV infection between 1983 and 1985. The current clinical status of the seropositive women is presently: generalized lymphadenopathy (n=6), AIDS—Related complex (n=2), AIDS (nzl) and unknown in one case. The male sexual partners of these women (all Belgian) are currently under inves— tigation. 9‘, This cluster demonstrates how HIV could spread heterosexually in an Euro- pean area with low prevalence of HIV infection from a few number of promiscuous men to a high number of female sexual partners without classical risk factor for HIV infection. TP83 TRANSMISSION OF HTLV III (HIV) IN INFANTS OF SEROPOSITIVE MOTHERS. ANDREA DE MARIA, 0.E.VARNIER*, G.MELICA**, F.PANTAROTTO**, P.CROVARI***, A.TERRAGNA, I Clinica Malattie Infettive, *Istituto di Microbiologia, **Istituto Ostetricia e Ginecologia, ***Istituto di Igiene, University of Genova,Italy. HIVinfection in pediatric age occurs most frequently in children of infected mothers by transplacental or perinatal transmission. To assess the risk for the fetus to acquire HIV infection during pregnancy we selected and followed up 36 infants born to HIV antibody positive drug addicts by vaginal delivery. None of them was breast fed or received blood or blood products. All the mothers were in WRI or WRZ disease stages. All the infants seen at birth had HIV antibodies at high levels, comparable to that of their mothers. 56% of those presently older than 6 months had progressively decreasing HIV antibodies and lost them between 7 and 12 months of age, suggesting only transplacental maternal antibody crossing without infection. This is further confirmed by the lack of clinical symptomatology and failure to detect HIV antigen in serum and in peripheral blood lymphocyte culture, as opposed to seropositive symptomatic children. The risk for the offspring of MRI or WRZ staged mothers of acquiring HIV infection during pregnancy can be presently estimated to be around 44%. Failure of detecting HIV antigen in serum and in cell culture may be useful as a diagnostic tool to rule out infection. 76 T284 Luck of Evidence for New Transmission Modes Among AIDS Patients. E. THOMAS STARCHERz II, TJ DONDERO, Jr., AR LIFSON, KG CASTRO, CR WHITE, JV CURRAN. Centers for Disease Control, Atlanta, Georgia, USA As of January 23, 1987, 29,582 AIDS patients (29,159 adults, 423 children) had been reported to CDC. Of these, 97% fit into risk groups that suggest a possible means of disease acquisition. For 32, means of acquisition is undetermined. Of all AIDS patients initially identified with undetermined risks and available for follow—up, 72% were reclassified because risk factors were identified (681) or the patient was found not to meet the surveillance case definition (42). 0f the 932 AIDS patients with currently undetermined risks, information is incomplete on 215 because of death (158), refusal to be interviewed (39), or lost to follow—up (18). 0f the remaining 717 patients, 523 are currently under investigation. No risk was identified for 194 patients who were interviewed or for whom other follow-up information was obtained. However, 39% of the patients (52/134) answering a standardized questionnaire gave histories of other sexually transmitted infections. Some of the patients with undetermined risks may not have HIV infection: for those on whom HIV-antibody information is available, 92 (32/349) tested negative compared with 12 (103/7330) for AIDS patients with identified risks. Lack of evidence for new transmission modes is clearest in the 5— to 15-year age group, which makes up 16% of the U.S. population. Sixty-six AIDS cases (0.2% of total cases) have occurred in this age group, which is exposed like other groups to casual contact with HIV-infected persons, insects, and environmental factors. Of these, 65 (98%) fit into established risk groups; the remaining case is lost to follow-up. The proportion of patients with undetermined risks has not increased significantly over time (p>0.10). "385 Serological Analysis of HIV gag Reactive Sera in a Blood Donor Population Using Both Viral and Recombinant Antigens D. TRIBE, D. REED. P. LYNDALL*, D. WINSLOW". S.R. PETTEWAY. et al.. E. I. DuPont de Nemours. Medical Products Department. Wilmington, DE., *Blood Bank of Delaware. Wilmington, DE.. **Wilmington Medical Center, Wilmington, DE. Sera from a normal blood donor population that display reactivity in an HIV-ELISA screening kit (DuPont) have been further analyzed using both viral and recombinant antigens. Two major paltems of HIV immunoreactivity have been identified in these HIV-ELISA reactives. The predominant class were gag reactive Ely non-reactive. and largely consisted of sera reacting with pl5/pl7 bands on immunoblot. These sera comprise 50% or more of HIV-ELISA reactives examined. Specificity of antibodies to HIV g was confirmed in several ways. including competition between viral and recombinant antigen for reaction with blood donor antibodies. Competition experiments also provided a direct demonstration that HIV»ELISA reactivity in these blood donors is largely caused by antibodies that react or cross-react with HIV gag. An HIV fl reactive class of sera was also identified in this population based on screening with both HIV immunoblots and with a recombinant (ENV9) ELISA. The ggg immunoreactivity may indicate exposure of this population to an as yet unidentified relrovirus. 11,86 Prevalence of HIV antibodies in healthy subjects and groups of ' patients in some parts of Tanzania FRED MHALU, E.MBENA, U.BREDBERG—RADEN, J.KIANUDK.NYAMURVEKUNGE, G.BIBERFELD et al., Muhimili Medical Centre, Dar es Salaam, Bukoba Hospital, Tanzania and National Bacteriological Laboratory, 5-105 21 STUCKHDLM, Sweden. Sera from groups of healthy subjects and from groups of patients collected in 1986 in Dar es Salaam (the capital of Tanzania), Bukoba (the capital of the Kagera region in the north west corner of Tanzania) and Arusha (in the north east part of Tanzania) were screened for antibodies to Human Immunodeficiency Virus (HIV) by ELISA (Organon—Teknika). All screening positive sera were also tested by 3 HIV competitive ELISA (Wellcome) and by Western blot analysis us— ing disrupted virions of the HTLV—III B strain of HIV as antigen. In Dar es Salaam Western blot confirmed HIV antibodies were demonstrated in 3. % of 192 pregnant women, 28.8% of 225 barmaids, 4.4% of 225 male blood donors, 9.25% of 400 male patients attending a clinic for sexually transmitted diseases, in 86% of 35 patients with herpes zoster and in 94% of 83 patients with clinical- ly suspect AIDS. In Bukoba the prevalence of HIV seropositivity was higher, namely 16% among 100 pregnant women and 14% among 36 blood donors while in Arusha only one out of 144 (0.7%) pregnant women and none of 42 barworkers tested were positive. HIV infection seems to be newly introduced in Tanzania and the extent of spreading of the infection differs in various parts of the country. TUESDAY, JUNE 2 TR87 Nbrtaiity, AIDS Incidence and Immunologic Abnormalities Among Intravenous Drug Abusers (IVDA) in New York City (NYC): A 5-Year Prospective Study. STANLEY H. NEISS*, 1.8. MARGOLIS**, R. ZELNICK**, H.M. GINZBURG”, D. FUCHS* , .J. *, et aI., *Nationai Institutes of Health, Bethesda MD, **Queens Hosp. Center, Jamaica NY,***Univ. of Innsbruch, Austria. IVDA in NVC were among the first recognized AIDS cases. In 1981 in NYC we Initiated the earliest prospective study of IVDA to evaluate cIinicaI and imnunoIogic abnormalities. HIV antibodies (Ab) were present in 46% of 54 IVDA by 1982. At least 24% of those HIV seronegative in 1982 had seroconverted by 1986. OveraII, at Ieast 60% of the originaI 60 IVDA now have HIV Ab. Seven seropositive IVDA have died, a totaI mortaiity of 42% :15% at five years (KapIan-Meier method, median foIIow-up 46 mo., range 0-63 mo.). Deaths were due to AIDS (3), car accident (1), and causes stiII under investigation (3). By five years, AIDS has been docunented in 17% 110%. M)rtaIity among the seronegative IVDA also has been substantiai: 9% t6% (median foIIow-up 54 mo., range 0-64 mo.), with deaths due to drug overdose and stabbing. None of the seroconverters has developed AIDS (median observation after seroconversion 12 mo., range 2-24 mo.). Mean T4a counts and T4a:18 ratios were significantly Iower in prevaient seropositive IVDA conpared to seronegatives (792 E 0.95 vs. 1175 & 1.40, p<0.02). Imnunoiogic pertubation was intermediate in seroconverters. Immune activation as measured by neopterin was increased among T4a deficient IVDA. The high mortaIity among IVDA from aII causes makes carefuI prospective foIIow-up of both seropositives and seronegatives essentiai. A review of post-mortem materiai from one subject who had died of an apparent overdose reveaied AIDS (Military Med 1511MB3). The excess mortality among seropositive IVDA may indicate under-ascertainment of HIV-reiated disease in IVDA. TBsa Relative Risks of AIDS for American Blacks and Hispanics RICHARD H. SELIK, M.F. Rogers, AIDS Program, Center for Infectious Diseases, Centers for Disease Control, Atlanta, Georgia, USA Although non-Hispanic blacks and Hispanics represent only 12% and 6%, res— pectively, of the 0.8. population, they constitute 25% and 14%, respectively, of the 29,497 AIDS patients of known race/ethnicity reported to the Centers for Disease Control (CDC) from June 1, 1981, to January 26, 1987. We studied their greater risk of AIDS, compared with that for non-Hispanic whites, in terms of their relative risks (RR), assessed as the ratio of the cumulative incidence of AIDS in a particular racial/ethnic group to the cumulative inci- dence in whites. The cumulative incidence was calculated as the total number of AIDS cases per million population of the same racial/ethnic group. Based on AIDS cases reported to CDC and population data from the 1980 census, the cumu— lative incidence of AIDS in whites was 98; that in blacks, 283; Hispanics, 290; and other groups (e.g., orientals), 63; these figures yielded RR of 2.9, 3.0, and 0.3 for blacks, Hispanics, and other groups, respectively, as com- pared with 1.0 for whites. The RR for blacks and Hispanics were greater for women (14.0 and l0.9) and children (14.0 and 9.1) than for men (2.9 and 3.1). When the analyses were stratified by the probable means of AIDS acquisition, the RR were greatest for transmission categories associated with intravenous drug abuse: for heterosexual intravenous drug abusers (IVDA) (21.3 and 23.5), for other persons whose heterosexual sex parters were IVDA (24.2 and 31.3), for children whose mothers were IVDA (36.4 and 25.5), and for children whose mothers had sex partners who were IVDA (14.5 and 23.1). The RR were also in- creased in association with male bisexuality, blood transfusion, and absence of any identified means of acquiring AIDS. Knowledge of these associations may be important in targetting AIDS prevention strategies for blacks and Hispanics. TP89 Five-Year (1982-1987) Prospective Clinical and Imnune Evaluation ' of Hemophiliacs Before and After Exposure to HIV. CHRIS TSOUKAS‘, H. STRAWCZYNSKII, F. GERVAIS*, J. SHUSTER*, P. GOLD*, *Montreal General Hospital, TMontreal Children's Hospital, Montreal, Canada. Immediately following the first appearance of AIDS among hemophiliacs in 1982 we evaluated 34 adults with severe classic hemophilia for immune defi- ciency, all were treated exclusively with lyophilized Factor VIII concen- trates. Initially all felt well and none had clinical manifestations related to AIDS although 68% had evidence of cellular immune dysfunction. To deter— mine the significance of this dysfunction and to assess the long term clinical outcome of this cohort, the grOup was followed for the next 5 years. They were examined and tested semiannually for T cell subsets, serum immunoglobulins, lymphocyte responsiveness to mitogens, energy, and viral serology. Serum samples were sequentially frozen and stored. Subsequent HIV serology by Western blot analysis revealed that initially 602 were scropositive in 1982 and by 1984 33/34 had seroconverted. Although all were initially healthy and asymptomatic, today 90% have clinical manifesta- tions of HIV disease. 521 (17/33) have persistent generalized lymphadenopathy (CDC Group III classification) and 38% (13/33) have AIDS or AIDS—related syndromes (or Group IV). One patient has died of AIDS related disease, two are critically ill following Pneumocystis carinii pneumonia and 5/33 have devel- oped severe life threatening thrombocytopenia. All HIV seropositive individ- uals currently display a spectrum of progressively deteriorating in vitro immune parameters that correlate significantly with time of exposEFe to HIV. We conclude that the majority of HIV seropositive severe classic hemophiliacs will develop severe HIV disease five years following exposure to the human immunodeficiency virus and almost all will display a progressive and significant deterioration of their immune status. 77 EPIDEMIOLOGY OF HIV INFECTION IN HONG KONG PCK LI EK YEOI-I WK CHANG YY CHAN SH LEE MEDICAL & HEALTH DEPARTMENT, HONG KONG. In a seroepidemiological study of the prevalence of HIV in Hong Kong, individuals from different groups were tested for HIV using a commercially available ELISA method. Positive results were by immunofluorescence and Western Blot. 74 of 38,293 individuals screened between April 1985 to 1986 were confirmed to be seropositive. Analysis of the results at intervals showed no increase in the prevalence of seropositivity. RESULTS OF HIV SEROIDGY RISK FACTORS IN 63 INDIVIDUALS TR90 KL THONG infection antibodies confirmed December 6-month1y TesHSd HIV l§g SEROPOSITIVE NgRAIDg AIDS Total Social Hygiene (STD) Clinic 35088 7(0.02%) Haemophiliacs 46 O 46 IV Drug Abusers l127 0(0 %) Hgmgggfigil/ 10 2 l2 Haemophiliacs 102 46(45.l%) Heterosexuals 2* 1 3 . . , . Patients With Cooley s anaemia306 0(0 %) with prostitute contact Haemodialysis patients 379 l(0.26%) Transfusi n 2+ 0 2 Health Care Personnel 219 0(0 %) reelpiengs __ * ’_ Sermen donors 85 0(0 %) 60 3 63 Government HospitalsSClinics 74S 8(1.1 s) *épgigctised IV drug abuse in Private Hospitals & Clinics 242 12(4.9 s) . . ————— -——————- + th r celved blood In 1984 38293 74(o.19s) 80 e Haemophiliacs with a history of imported factor VIII transfusion, homosexuals and bisexuals, and heterosexuals with history of sexual contact with prostitutes constitute high risk groups for HIV infection in Hong Kong. The risk of transfusion—related HIV infection should be reduced by the donor screening programme instituted since August 1985. TP91 Modelling the Incidence of Acquired Immunodeficiency Syndrome (AIDS) in New York, San Francisco and Los Angeles JOHN PICKERING, J.A. WILEY, L.E. LIEB, J. WALKER, and G. RUTHERFORD, Dept. of Entomology, Univ. of Georgia, Athens, GA; Survey Research Center and San Francisco Men's Health Study, Univ. of California, Berkeley, CA; County of Los Angeles, Dept. of Health Services, CA; City of New York, Dept. of Health, NY, and City and County of San Francisco, Dept. of Public Health, CA. Vith an epidemic model we explore the biology and sociology of AIDS incidence and forecast new cases. Our model assumes that AIDS can be modelled as a sexually transmitted disease. Its parameters reflect (1) how long AIDS takes to develop after exposure to the infectious agent, (2) when infected individuals are contagious, (3) decreases in transmission rates because of behavioral changes, and (4) saturation—-the removal of susceptible individuals through infection. Declines in anal/rectal gonorrhea cases in New York and San Francisco are used in modelling the impact of behavioral changes. By November, 1986, New York, San Francisco, and Los Angeles had over 8,031, 2,546, and 2,360 AIDS cases, respectively. Each city’s cumulative number of cases doubled in the 10-13 months before July, 1985, but may not continue to increase at this rate. The model shows how AIDS incidence in the cities could level off and even start to drop by 1991, because of saturation and behavior. However, a sensitivity analysis of the model’s parameters shows that there are insufficient data to choose between radically different forecasts. Before accurate forecasts can be made, more data are needed on (1) the distribution of development times, (2) the infectivity of individuals, (3) the proportion of infections that develop AIDS, and (4) behavioral changes. Judged by the model’s fit to the cases reported by November, 1986, it appears that these cases generally were diagnosed 3-4 years after exposure to the agent and were most infectious in the months immediately after exposure. 11.292 Evaluation of first and second generation (confirmatory) assays for antibodies to HIV P. Nico LELIE, J.G. HUISMAN et a1.(1) Central Laboratory of the Netherlands Red Cross Blood Transfusion Service, (CLB), incorporating Lab. of Exp. and Clin. Immunology University of Amsterdam. The sensitivity and specificity of six commercial enzyme immunoassays (EIAs) for antibodies to HIV has been evaluated in 6488 serum samples (Lancet, August 30. 1986: p.483-486) (1). This panel and sequential sera from 12 individuals who seroconverted for anti—HIV were used to compare the first and second generation EIAs from three manufacturers (Abbott, Organon, Wellcome) and three confirmatory assays, i.e. Western Blot (WB, Biotech Dupont): competitive immunoassay for separate detection of antibodies to HIV envelope and core (CIA, Abbott) and a home-made radio immunoprecipitation assay (RIPA—CLB). confirmatory tests and second generation EIAs were significantly more sensitive in detecting antibodies early after HIV infection than the first generation BIAS. The earliest detectable antibodies in the confirmatory tests were anti-p24 and anti-gp120/16D in WB; anti—envelope in CIA and anti—p24 in RIPA. Ihe anti-core CIA did not detect anti-p24 responses in approximately 10‘ of asymptomatic seropositive individuals. The antibody levels against envelope proteins gp 160/120/41 persisted during transition to AIDS, whereas antibody titers to 924 dimiminished or disappeared. Follow up studies showed that false positive reactions were observed in confirmatory tests. The respective frequencies in a panel of tricky sera (n-293) and of blood donors (n=5000) were W.B.: anti-p24 1,7‘ , 0.18% yCIA anti—envelope: 0,3t . 0.02% 7 RIPA anti-p24: 0‘ , 0.06!.The new generation EIA'S are important tools to establish early antibody responses in patients and blooddonors exposed to HIV. The TUESDAY, JUNE 2 TP93 PRELIMINARY RESULTS OF A SURVEILLANCE SYSTEM OF HIV PEDIATRIC ' INFECTION GIUSEPPE IPPOLITO, PEDIATRIC AIDS AND HIV INFECTIONS VORKING GROUP, Coordinated by Latium Region Epidemiologic Unit and Children's Hospital Bambino Gesu- Rome— Italy A surveillance system of HIV infection, based on compulsory notification by laboratory physicians of every positive subject together the relevant data (place and date of birth, sex, place of residence, risk factors) was set up in Latium, a 5.000.000 inhabitants region of Italy, in 1985. An active working group to trace seropositive mothers, contact and perform clinical follow up on babies at risk was established. 80 babies (1 hemophiliacs, 2 transfused and 77 child born HIV positive mother) had a positivity for anti-HIV antibodies until October 1986. 73 seropositives have been enrolled in a follow-up study. Mean time of observation was 10.3 months (range 1-36), for a total of 749 person/month of observation. Nine cases of AIDS have been observed. incidence rate, in a period of 36 months, is .123 (CI 95% .058—.221). Fourteen children (.122 - C1951 .109-.301) have lost the anti-HIV antibodies during the first year of life (mean 8 months, range 5-12). Thirty-five children (.479 CI 951 .361-.600) younger than l year (mean time of observation: 4.1 months) were positive at the end of the observation time. Six subjects (.062 C1951 .031—.17) were seropositive and asymptomatic at the end of an average observation period of 17.8 months. Five (.068) children showed a persistent generalized lymphsdenopathy after a mean 12.4 months of observation and four babies (.055) costitutional diseases and/or secondary infectious diseases. T394 Surveillance of AIDS In India With Special Reference to Union Territory of Delhi. P.N.Sehgal, .KUMARI,ARVIND RAI,Natlonal Institute of Communicable Diseases, Delhi-110054 (INDIA). Following the first confirmed evidence of AIDS virus infection in India in April, l986, a massive surveillance campaign was launched to screen high risk individuals across the country. From July through December,1986, a total of 5,000 serum samples were collected lfrom specified high risk individuals from Union Territory of Delhi. Of them 3268 were from males and the rest (I732) females, mostly between 20-45 years of age. The samples belonged to patients attending 81‘ D clinics (2789), prostitutes (408), jail inmates (413), drug addicts (49), professional blood donors (1057), chronically ill patients referred from hospitals from HTLV- 111 antibody screening (246), foreign students (8) and the patients who underwent by-pass surgery abroad (30). All the samples were subjected to Wellcozyne H'I'LV-III ElA. Only one sample yielded a strong positive result in ELISA confir- med by Western blot. Samples from two male patients attending STD clinics yielded positive ELISA results but only one gave a mild positive ( result in Western Blot. These findings Indicate that AIDS virus infection in this part of the country Is probably at a very low key, but continued surveillance is warranted to keep a close vigil over the situation. p24 band only) 113.95 ACTUAL SITUATION OF HIV INFECTIONS Ill FRENCH POLYNESIA E. CHUNGUE, F. FLYE SAINTE MARIE, .l.L. CARTEL, G. PAPOUIN, S. CHANTEAU and J. RUUX, Institut Territorial de Recherches Médicales Louis Malardé, B.P. 30 Papeete-TAHITI Since July 1985, a serological survey is carried out in 682 subjects belon- ging to different groups at risk for AIDS. Positive sera in ELISA were confir- med by immunoblotting. The sero prevalence in January 1987 is : 0/33 hemodialysis patients transfused 1n Tahiti 0/131 female prostitutes 1/138 male homosexual (transvestites). He never left French Polynesia and reported foreign sexual partners. 10/244 (9/170 M, 1/74 F) homosexual or bisexual men and patients attending private practitioners or STD clinic for AIDS counseling. 9 of them have lived or travelled often in countries where AIDS is endemic. 6/125 (4/54 M, 2/71 F) permanent residents operated mostly between 1981 and 1985 for heart disease and intensively transfused in other countries (France essentially) before blood screening is established. 1/11 (5 M, 6 F) household contacts or sexual partners of 3 seropositive cases. The overall prevalence rate of HIV antibodies is 2.5 % in the high risk population and 0.1 %. as referred to the total population (170 000 inhabi- tants). ARC has been diagnosed in 4 of them. Introduction of the AIDS virus is likely recent since no instance has been found yet in more than 8 000 blood units tested in the local transfusion center. As a matter of fact, HIV has been brought into French Polynesia in part, by a much-travelled class of the population involving homosexual and bisexual men essentially and in the other hand by heterosexual patients who underwent heavy surgery in foreign country. 78 Tags Genetic Aspects of AIDS in Trinidad. C. BARTHOLOMEH: FARLEY CLEGHORN', V. HILSON*, B. MAHABIR*, AJIROOK, A.S. FAUCI. The University of the West Indies*, Port of Spain, Trinidad and the NIH, Bethesda, Maryland, USA. Trinidad has a population of 1.2 million comprising people of African descent 41%, Indian descent 41%, mixed race 16%, Chinese 1% and Caucasians 1%. To date a total of 144 cases of AIDS have been seen in Trinidad. Of these 133 have been in people of African and mixed African descent, 7 in people of Indian descent, 3 in Caucasians and 1 Chinese. The conmon opportunistic infections seen are candidiasis, toxoplasmosis, histoplasmosis and cryptococcosis. Less conmonly seen is Pneumocystis carinii pneumonia and Kaposi's sarcoma is rare. In a survey of 106 healthy homosexual men in Trinidad in 1983, 36/90 (40%) of those of African and mixed African descent were HIV seropositive compared with 6/16 (37.5%) of those of Indian descent. As the prevalence of homosexuality appears to be equal in the various ethnic groups in Trinidad the possibility of a genetic factor associated with the relative paucity of cases of AIDS in Indo-Trinidadians was considered. Preliminary studies of antibody dependent cell-mediated cytotoxity (ADCC) have shown that HIV positive Indo-Trinidadians without disease have higher levels of ADCC (mean 29.4%) than Afro-Trinidadians without disease (mean 14.8%). Initial studies of HLA haplotypes among 130 healthy males in Trinidad have shown that HLA Dr 5, which is present in 24.8% of black Africans is absent thus far in 70 Afro-Trinidadians while present in 8.5% of Indians. In addition, there is a relative absence of HLA Dr w6 (4.3% vs 20.2%) and particularly HLA Dr 1 (0% vs 15%) in persons of Indian descent in Trinidad compared with those of African ancestry. These genetic differences could possibly expain the discrepancy in the occurence of AIDS among Trinidadians of African and Indian descent. ":97 AUTOLOGOUS KILLING MECHANISMS IN HIV xmcnos. _H_H Man, ' SF Purvis, Department of Medicine, Case Western Reserve University and University Hospitals, Cleveland OH. Longitudinal studies performed among hemophiliacs (H) infected by the human immunodeficiency virus (HIV) reveal a progressive loss of CD6 lymphocytes and increased numbers of C016 and activated CD8 cytotoxic lymphocytes. He asked if lymphocytes of HIV infected H could kill autologous cells. In A h. chromium release assays, unstimulated H lymphocytes (n-9) demonstrated significant cytotoxicity against autologous cells (5.2t2.0! lysis) (mean t SE), whereas controls' (C) cells (n-12) demonstrated no autologous killing (0.510.31 lysis, p<0.02). After culture for seven days with irradiated autologous peripheral blood mononuclear cells (n-7) nonadherent (NA) H cells demonstrated enhanced killing of autologous PHA blasts when compared to C (n-7) (Il.5t4.8 vs 4.112.01 lysis p<0.05). After stimulation by alloantigens, H NA cells demonstrated greater killing of autologous targets than C HA cells did (19.414.2 vs 10.0i2.51 lysis, p< 0.01) and were activated more than C NA calls to lyse both allogeneic (stimulator) targets (p<0.03) and unrelated allogeneic targets (p<0.05). Cold target inhibition studies demonstrated that K562 tumor cells and unrelated EHA blasts inhibited lysis of autologous targets. Yet cell separation studies revealed that autologous killing was mediated by CD8 lymphocytes and was unaffected by depletion of C016 cells. Enhanced autologous killing was seen in 3 HIV-infected homosexual men but not in.3 HIV-aeronegative H. Thus, lymphocytes of HIV—infected persons possess low levels of cytotoxic activity against autologous lymphocytes and show increased activation by ailoantigens to lyse nonspecifically autologous and allogeneic cells. Autologous killing may contribute to the progressive lymphopenia of HIV infection. “3.98 Persistent Co-lnfection of T Lymphocytes with HTLV-ll and HIV and the Role of Syncytium Formation in HIV-Induced Cytopathic Effect. DAVID C. MONTEFIORI‘, W. EDWARD ROBINSON and WILLIAM M. MITCHELL, VanaerEI t Unwersuty, School of Medicine, Nashville, Tennessee. We previously demonstrated a high permissiveness of HTLV-lI-transformed T lymphocytes (C3) to human immunodeficiency virus (HIV) infection lgvltro and that this infection results in the lysis of cells (D.C. Montefiori and WM. Mitchell. Virolog , fl, 726-731, 1986). We now show that a small percentage of HIV lnfectedCB cells resist cell lysis. grow continuously in culture and express antigens of both viruses. High levels of reverse transcriptase activity found in the culture fluid of these co-infected cells was associated with the presence of fully infectious HIV and an absence of detectable infectious HTLV-ll. Virus production in C3 cells co- infected with HIV isolate HTLV-III was approximately 3~fold greater than in C3 cells co-infected with the HIV isolate LAV, a result which suggests that HIV genomic diversity may give rise to differences in replicative capacities. Lysis resistance was found to be a cellular-determined function in that HIV produced in cultures of C3/HTLV-III cells retained the capacit to elicit a lytlc response upon repeated infection. Small syncytia were rarely 0 served in cultures of C3 and non-Iytic C3/HIV cells whereas large syncytia were in abundance during the lytic phase of co- infection, a result which supports a role for syncytium formation in the mechanism of HIV-induced cytopathic effects. The results of these studies also demonstrate that there exists a lack of HIV interference by HTLV-ll infection, and that HTLV-ll transformed lymphocytes could act as a chronic reservoir for HIV l_n vivo. These findings have important medical implications in view of the high preva ence of HTLV-ll antibodies in HIV antibody positive and negative individuals at risk for AIDS (Robert-Gumffe_t a_l.. JAMA g, 3133-3137,1986). TUESDAY, JUNE 2 T899 mm. MICHAEL S WEAVER, MT SCHECHTER, WI BOYKO, B DOUGLAS, B WILLOUGHBY, AW MCLEOD, et al. The Vancouver Lymphadenopathy-AIDS Study, St. Paul's Hospital, University of British Columbia, Vancouver, BC, Canada. The long term effects of HIV infection were evaluated in a cohort of homosexual men by comparing clinical and lab parameters obtained from 2 visits a mean of 18 months apart in groups of I48 persistently seropositive and 287 persistently seronegative men. Differences between the groups were present at each visit with the seropositive men exhibiting lower CD4 counts, higher CD8 counts, lower CD4/CDS ratios, higher Clq binding, higher IgG and IgA levels, lower Hgb, and lower lymphocyte counts. More important, comparison of the differences between visits in the positive and negative groups, revealed that the seropositive group underwent a significant mean decline in the CD4/CD8 ratio (-0.13 vs +0.05; p=.013), and significant mean rises in the Clq binding (+4.7 vs +0.5; p<.001), in the IgG (+92 vs -2; p<.001) and in the IgA (+16 vs +1; p<.001) as compared to the seronegative group. Seropositive men were at elevated risk of developing symptoms and lymphadenopathy, though these risks did not progress with time. Comparisons of parameters obtained a mean of 21.4 months prior to ‘ a ‘ inII , “vemenwho 1 ‘, p g ‘toAIDSand1345eropositivemenwhodid not, revealed lower CD4 counts (450 vs. 739; p<.001),lower CD4/CDS ratios (0.65 vs 1.14; p<.001), higher Clq binding (20.7% vs. 13.6%; p<.001), lower Hgb (14.6 vs 15.1; p=.088), and lower lymphocyte counts (1638 vs. 2041; p=.041) in those who progressed to AIDS. Moreover, between antecedent visits, those who progressed to AIDS experienced greater mean declines in CD4 count (-155 vs ~40; p=.074), in Hgb (-1.1 vs -0.1; p<.001) and in WBC {-1000 vs >351; p=.079) than the seropositive AIDS-free group. Although these data document long term effects of HIV infection in a seropositive cohort, about 25% of persistently seropositive men maintained normal CD4/CD8 ratios, suggesting the possibility of one subgroup of men who may be resistant to the effects of HIV infection, and another who are particularly susceptible to the progressive effects of HIV that precede the development of AIDS. Effects of long term seropositivity to W in a cohort of lumsexual T2100 Antibodies to the transactivating protein of HIV, tat3 and the induction of HIV antigen expression i3 vivo. EILLY J.A. KRONE*, Chr. DEBOUCK**, P. HEUTINK*, J.M.A. LANGEf F. DE WOLF*, and J. GOUDSMIT*; *Virology Department, University of Amsterdam, Netherlands, **Smith Kline and French Laboratories, Philadelphia, PA, USA. To obtain large amounts of the tat3 protein, a plasmid was constructed in which the 3th to last tat3 codons were fused to the first 52 codons of the E.coli galactokinase gene in the pOTSKF33 expression vector. The fusion protein was induced in E.coli using nalidixic acid and purified using preparative SDS-PAGE. The purified fusion protein had a molecular weight of 17 KD and was used as antigen for immunoblotting and enzyme-linked immunosorbent assays (EIA). The presence of HIV Ag was evaluated by EIA (Abbott Labs, N. Chicago, 111.). Sequential sera of 86 individuals, collected over a period of two years were used in this study Twenty-one of these individuals seroconverted for antibodies to HIV and 65 were HIV-Ab seropositive at entry in the study. Among the HIV-Ab seropositives 21 were HIV—Antigen positive throughout the study and 27 seroconverted for HIV-Ag. The presence of antibodies to tat3 was closely related to expression of HIV-Ag in serum (p<0.01). Seroconversion for antibodies to tat3 was observed prior to or concomitant with seroconversion for HIV—Ag. Individuals with a prolonged HIV antigenemia showed a steady decline in antibody titers to tat3 with time. These results present evidence for lg vivo regulation of HIV gene expression by the tat3 protein. TP101 Characterisation of the T-lumphocyte Response to Primary ' HIV Infection. DAVID A. COOPER*#, B. TINDALL *, R.PENNY#. *NHIMRC Special Unit in AIDS Epidemic ogy and Clinical Research. Sydney, Australia. #Centre for Immunology St. Vincent's Hospital, Sydney, Australia. Multiple T-lymphocyte determinations were availabe on 19 homo- sexual men for up to 500 days following primary HIV infection. In all subjects the initial response to HIV infection was a marked decrease in the total lymphocyte count and in the absolute numbers of circulating T4+ and T8+ cells; the T4+:TB+ ratio remained normal. Within 14 days the lymphocyte count began to rise with a T8+ subset increasing proportionally more than the T4+ sub- set, leading to an inverted T4+:T8+ ratio by day 20. This period was followed by an increase in the total lymphocyte count (and subsets) above base line levels. This relative lymphocytosis lasted up to two months and the major contributing subset was the T8+ lymphocytes, followed by an incomplete reduction in T8+ lymphocytosis. The ensuing months were characterised by a return of the T4+ lymphocytes to near-baseline levels, but a maintenance of a high T8+ response and an inverted ratio. These changes represent three distinct phases: an acute symp- tomatic period with lymphopenia, a recovery period with a T8+ lymphocytosis, and a longer term period of asymptomatic HIV infec- tion with a normal level of T4+ lymphocytes, slightly increased T8+ lymphocytes and an inverted T4+:T8+ ratio. Further investigations of the mechanisms of these changes and the role of T8+ lymphocytes in limiting HIV infection may improve understanding of immunoregulation of HIV infection. 79 TP-Ioz Rapid Detection of Human Immunodeficiency. Virus Antigens in ' Lymphocytes by Immunogold Scaning Electron Microscopy. RAFAEL NAJERA, M.I. HERRERA, R. de ANDRES,I. SANTA MARIA. A. TENORIO, L. IE NOZ. Centro Nacional de Microbiologia, Virologia e Inmunologia Sanitarias. Instituto de Salud Carlos III Majadahonda,(Madrid), Spain. The observation by scanning transmission electron microscopy (STEM) of —— gold immunolabelled Human Immunodeficiency Virus (HIV) infected cells might be a new approach to rapid diagnosis of AIDS at the early phase of infecti— on. It combines both the morphological information and rapid procedures of scanning electron microscopy (SEM) with SEM of lymphocytes from 13 HIV posi tive individuals and from HIV infected cultures lymphocytes reveals the p:3 sence of giant cells with characteristic "spongy" surface appearance that - suggest viral infection. In 4 patients, other unnusual spherical multiface— ted structures (5—18 um.) have been also found. They could correspond with a process of gene amplification and could indicate virus production at low level. A more precise detection of the presence of HIV antigens in these ”spongy" cells has been achieved by their specific indirect inmunolabelling, using - anti-p17 and anti—gp41 monoclonal antibodies as sprimary antibodies and 40 nm gold—labelled goat anti—mouse IgG as secondary antibodies. The use of - STEM techniques and backseattered electrons imaging for gold detection pro- vides a very sensitive technique for antigen detection at and below the -- cell surface. Paired electron micrographs have been taken showing that "spongy” cells have a particulate gold content, indicating HIV infection. “2103 Normal Neutrophil Phagocytosis but Inpaired Chemotaxis in Homo- sexual Male Patients with AIDS, ARC and Neither Disorder LAWRENCE A. OWE", *DIVIS THIND**, MILAN FIALA", DAVID R. REWARD", DOMENIC CASAREALE". *Eisenhower Medical Center. Rancho Mirage. CA. Although the target cell for HIV infection is acknowledged to be the T4 helper cell. monocyte. macrophage and B-cell function is also adversely affected by the retrovirus. We and others have previously reported an increased incidence of unusual and recalcitrant bacterial infections in patients with AIDS as well as homosexual wales suggesting impairment in neutrophil function. Chemotaxis and phagocytosis are critical events in the effector functions of granulocytes. Thirty-one homosexual or: bisexual males were studied for neutrophil chemotaxis using zymosan—activated serum in a Boyden chamber and phagocytosis utilizing latex spheres. Twenty-three patients had AIDS, 5 had ARC and 3 had neither. Seventeen of 23 (74%) with AIDS. 4 of 5 (80%) with ARC and 2 of 3 (67%) with neither disorder expressed defective chemotaxis but normal neutrophil phagocytosis. No distinguishing clinical or laboratory characteristics could be discerned within each group that separated normals from those with abnormal leukocyte chemtaxis. It is concluded that defective chemotaxis is oamnn in patients with AIDS. ARC. and in otherwise healthy HIV antibody-negative homosexual males. The etiology of this defect will require additional studies. but appears to be related to lifestyle rather than to HIV infection. TP104 In vitro synthesis of antibodies against HIV-1 components. ALBERTO AMADORI", A. DE ROSSI*, G.P. FAUUCNEIR-VAILE”, C. GIAQUIN’I‘O"*, E. FRANOWIIIA“*, L. CHII-Jm-BIANCHP. *Inst. of Oncology, ”Pediatrics Dept., ***Infectious Disease Div., University of Padova, Italy. We studied the in vitro synthesis of antibodies directed against human immunodeficiency virus, type 1 (HIV-1, IAV/HTLV-III) components (HIV-Ab) from peripheral blood lymphocytes of 30 seropositive individuals. A significant amount of HIV-Ab was detected by an IgG-ELISA assay on culture supernatants of unstimulated cultures. Mean absor‘bance values in the patient group was 1.104:0.381 SD, whereas in the control group n‘ean values of 0.0201002 SD were found. The phencnenon reflected a de novo Ig synthesis, as shown by the inability of puromycin—treated cultures to produce HIV-Ab. Moreover, spontaneous HIV production was detected within the first 24 hr of culture, suggesting an in vivo activation of antibody-forming cells. When PBL were cultured in the presence of pokeweed mitogen, a significant difference in HIV-Ab production between seronegative and seropositive individuals was still observed. When examined by the Western blot technique the supernatants frcxn seronegative subjects gave negative patterns, whereas all those frcm seropositive individuals were reactive with different virus proteins. A general correlation between serum and supernatant Western blot reactivity was observed, although in individual cases some antibody specificities were not detected in culture supernatants. The present in vitro model could be an useful tool to investigate the inmonobiology of HIV—1 infection. TUESDAY, JUNE 2 TP.105 P.5ALMON. J.C.GLUCKMAN, D.KLATZMANN. UFR Pitié —salpétriere, Paris, FRANCE. HIV infected cell lines display decreased CD4 membrane expression and mRNA levels after long-term cultures. Two mechanisms could explain such bulk reduc— tion in CD4-gene transcription: (1) direct genomic interaction between HIV and CD4; (2) progressive selection of individual CD4 low-producing cells.Using the cytodot technique with a p—actin internal standard, we sequentially performed semi—quantitative determination of CD4 mRNA levels in normal lymphocytes and various cell lines before and after infection with HIV. Normal or slightly elevated CD4 mRNA was observed during early ((2 weeks) HIV replication in nor- mal CD4+ lymphocytes. CD4 mRNA remained also normal at the chronic replication phase (>2 weeks) in CEM derived clones. In both. cell types, HIV replication led to the complete disappearance of detectable surface CD4.Low CD4— expressing HIV—resistant cells eventually emerged from the lines while the clones subse— quently died from cytopathic effect. Altogether all these findings rule out any direct genomic interaction between HIV and CD4,arguing for the selection of low CD4—expressing cells in heterogeneous cell lines. They confirm and empha— size previous results that strong CD4 expression is a requisite for the occur- rence of significant HIV cytopathic effect. CD4—gene transcription is not impaired by HIV replication. 'rR106 Regulation of HIV Expression in Acutely Infected‘Promonocyte Cells and in Chronically Infected Promonocyte Clones THOMAS M. FOLKS*, J. JUSTEMENT*, A. KINTER*, G. POLI*, J. ORENSTEIN**, AND A.§. FAUCI*, *NIH, Bethesda, MD, **G.N. Univ., Washington, D.C. The monocyte has emerged as a potentially important cell in the pathogenesis of human immunodeficiency virus (HIV) infection. Successful HIV infection of normal monocytes in vitro has been achieved. In addition, The promonocyte cell line, U937, has been demonstrated to be susceptible to infection with HIV, and the level of HIV expression has been shown to be under regulatory control with cytokines such as GM-CSF and INF-v. The present study has investigated the effect of phorbol myristate acetate (PMA) an inducer of monocyte differentiation, on the initial infection of U937 cells with HIV and on chronically infected U937 clones. Following acute infection of U937 cells wifih HIV the cell line can be inhibited from producing virus if treated with 10 M PMA. Concomitant with this inhibition, PMA induces differentiation of U937 cells as manifested by adherence, granule formation, increase in surface density of CR3, and down—modulation of CD4 (the HIV receptor). In contrast to the acutely infected U937 cells, clones derived from the chronically infected U937 population which manifest only a very low level of viral productivity show an increase in the level of HIV expression after PMA induction. EM studies of these clones indicated that PMA also induced increased endocytotic vesicles containing many HIV particles. 12 situ immunofluorescence of these clones stained with pooled sera from AIDS patients showed an increase from 2% to 30% positivity after PMA treatment. These studies lend insight into the role of monocyte differentiation in the susceptibility to HIV infection as well as provide a model at the clonal level to delineate latency or chronicity of HIV infection of monocytes and the signals required_for conversion to high level viral expression. T2107 THE SKIN REPRESENTS A SITE OF VIRUS REPLICATION DURING INFECTION WITH HUMAN IMMUNODEFICIENCY VIRUS (HIV). E.Tschachler*,V.Groh*,S.Gartner’,K.Rappersberger**,P.Schenk+, G.Stingl**et al.*Laboratory of Tumor Cell Biologie,NCI, NIH, Bethesda, MD,**Dept. of DermatologyI, +Dept. of OtolaryngologyII, University of Vienna Medical School,Vienna, Austria. The skin is a heterogenous organ consisting of cells of differ- ent ontogenetic origin. Epidermal Langerhans cells(LC) represent a persistent, distinct population of antigen presenting leuco— cytes within the skin. We have recently demonstrated that LC of HIV—infected individuals react with monoclonal antibodies direc— ted against HIV specific core proteins p17 and p24 - a finding highly indicative for the presence of HIV within these cells. Extensive electronmicroscopic analysis of skin and mucosal biopsies from an AIDS patient with anti pl7/p24 reactive LC now revealed mature HIV—like virions in the extracellular space sur- rounding LC as well as developmental forms of HIV- like particles budding from LC surface membranes. Moreover, cocultivation of a punch biopsie from normal appearing’WSKYn”’off"tfiI54’AIDS patient with mononuclear phagocytes from a non-infected donor, resulted in the detection of high levels of reverse—transcriptase activity in the culture supernatant. This latter finding implies that active virus can be rescued from the skin of HIV infected indi- viduals.0ur findings conclusivly confirm that (I) LC are an actu- al target for HIV infection and production, supporting the view that besides T cells , cells of the monocyte /macrophage lineage are a major target population of this virus (II) the skin may serve as a viral reservoir during the course of HIV infection. 80 TP108 HIV Binding to the CM Molecule: Conformation Dependence ' and Antibody Inhibition. J.STEVEN MCDOUGAL, J.K.A. NICHOLSON, G.D. CROSS, S.P. CORT, M.S. KENNEDY, A. MAHLE, Centers for Disease Control, Atlanta, GA. The human Immunodeficiency virus (HIV) binds to CD4+ T cells via a complex of the viral envelope glycoprotein gp110 and the CD6 molecule. We treated virus with a variety of physical, chemical, and enzymic agents to determine their effect on the capacity of HIV to bind to CD1»+ T cells. Reduction and alkylatlon (but not alkylation alone) and trypsin digestion (but not glycolytic enzyme digestions) of HIV destroyed its capacity to bind. Human sera reactive with HIV universally inhibited virus binding, but the binding inhibition titers were only weakly correlated with anti-gpIIO titers. Absorption, elution, and crossabsorption of anti-HIV serum with immobilized native or reduced and alkylated virus provided evidence for conformation-dependent antibodies that are potent inhibitors of virus binding. Taken together, these results indicate that the CD5 binding site of gp110 requires a proper tertiary protein conformation that is dependent on covalent disulflde bonds and that conformation-dependent antibodies are elicited that are potent inhibitors of virus binding. TP109 Frequency of Infected CD4 Cells After in vitro Exposure to HIV ' Determined by Limiting Dilution Analysis. LINDA S. MARTIN, J.S. MCDOUGAL, Centers for Disease Control, Atlanta, CA. We developed a limiting dilution assay for determining the frequency of infected cells (FDIC) after in vitro exposure to HIV. Cells were incubated with HIV, washed, diluted, and cocultured with phytohemagglutinin (FHA)— stimulated lymphocytes in microcultures. The frequency of positive cultures conformed to a Poisson distribution. The assay was sufficiently sensitive to detect a single infected cell as assessed by analysis of HIV-infected H9 cells. The FOIC depended on the ratio of virus to cells used for inoculation, 1.2. the multiplicity of infection (MOI). For example, the FDIC for FHA-stimulated CD4 cells Increased from I in 24 at a MOI of 0.99 to 1 in 1 at a MOI of 99. FOIC increased with increasing time of incubation with virus and reached a maximum of I in 5 to l in 1 at 24 hours for FHA-stimulated CD4 cells. Inoculation of unstimulated CD4 cells under the same conditions yielded FOIC that were substantially lower (less than 1 In 100). Activated cells were treated at various times after exposure to HIV with trypsin under conditions sufficient to inactivate accessible HIV and to remove the HIV-binding portion of the CD4 molecule. There was no difference in FOIC with or without trypsin, suggesting that the physical manipulations used remove surface-bound virus. In contrast to these results, HIV binding to the CD4 receptor is trypsin—sensltive, occurs much more rapidly, and is equivalent in activated and nonactivated CD4 cells, indicating that the limiting dilution results reflect a more rate~limit1ng step in the establishment of cellular infection, such as penetration of virus. We conclude that virtually all CD4 cells, under optimal conditions of activation and incubation, can be infected with virus. However, establishing infection is more efficient in activated cells, possibly related to increased internalization and cycling of the CD4 molecule. TR110 Production of Antibody by Circulating B Cells of HIV-Seroposltivc Subjects. SUSAN ZOLLA-PAZNBR‘, H. MIZUMA‘, V. GIANAKAKOS‘, A. PINTER" and l. HDNNEN“. New York Veterans Administration Medical Center‘, New York University Medical Center', and Public Health Research Institute... New York, NY. Cells producing antibody (Ab) do not normally circulate except during a short time following immune stimulation. In patients infected with HIV, however, circulating B cells were found to spontaneously secrete anti-HIV antibodies in 20 of 22 class. For these experiments. 0.1-5.0 x 10' peripheral blood mononuclenr call! (PBNC) were cultured in microtiter walls withgpg mitogen or antigen for periods of 1-15 dnys. At 5 x 105 cells/well. cells from five control subjects produced no detectable anti-HIV Ab (measured with commercial ELISA kits) over the entire culture period; at this cell concentration. cultures from 5 of 6 AIDS patients spontaneously produced Ab. Cells from 11 of 11 patients with ARC produced Ab and cells from 4 of 6 HIV- seropositive subjects without AIDS or ARC (high risk patients) also produced Ab. Positive cultures showed the presence of detectable Ab within 24 hr.. indicating that these cells had been stimulated 11 vi! . Incorporation of HIV viral lysutol into the medium (0.125-l.0 pg/ml) for varying periods of time did not enhance Ab production. By a radio—inmunopreclpitntion nus-y, Ab production appeared polyolonal. with reactivity primarily directed against gp 41- SP 120 and reverse transcript-1e. 'hen PBNC were cultured at lower concenttltions, wells containing Ab-producing cells were detected in all experiments at 2.5 x 10‘ cells/well and in 75—80% of experiments at 1.0 and 0.5 x 10’ cells/well. No Ab production was detected It (0.5 x 10‘ calls/wall. The presence of circulating Ab—ptoducing cells may reflect continual antigenic stimulation by replicating virus in infected subjects. TUESDAY, JUNE 2 TR111 A genetic factor affecting susceptibility to HIV infection and to disease progression. LESLEY-JANE EALES, KE NYE, JM PARKIN, JN WEBER, SM FORSTER, AJ PINCHING, ET AL. St Mary's Hospital and Medical School, LONDON W2. UK. Whilst examining serum factors in AIDS patients, many were noted to have a rare phenotype of Group specific component (Gc). This prompted an indepth study of Go phenotypes in 214 subjects from existing cohorts of homosexuals at risk from, or infected by HIV, classified according to current clinical status, compared with 122 healthy male heterosexual seronegative controls. Sera were analysed by isoelectric focusing on thin layer polyacrylamide gels containing ampholytes (pH 4.5- 5.4). 30.22 of AIDS patients were homozygous for Go 1 fast (cf controls 0.8%; p<0.001); other seropositive clinical groups also more commonly had Gc 1f. Seronegative asymptomatic homosexual contacts of AIDS patients (AH-p) lacked this phenotype. By contrast, AIDS patients lacked the Sc 2 phenotype, but this was more common in the AH-p group (251) than in controls (9%; p<0.01). A chi squared trend test showed a highly significant association between the CC 1 fast allele and progression to AIDS (p<0.0001) and the reverse with Gc 2 (p<0.05). We propose that Gc is involved in viral entry into host cells and that the different allelic forms of Gc, which vary in sialic acid content. dictate its ease. TR112 Serum Non Organ Specific Autoantibodies during Infection of Human Immunodeficiency Virus (HIV). FABIO CASSANI, L. BAFFONI, E. RAISE°, L. SELLERI, M.G. CATALINI°, F.B. BIANCHI. Clin. Med. II Universita, °Dip. Mal. Infett. Osp. Maggiore, Bologna, ITALY. HIV infection is associated with pclyclonal B cell activation and hyperganmla- globulinemia. Autoimmune features may be present. Data are lacking about the cg currence of serum non organ specific autoantibodies. 6b HIV infected subjects, including healthy carriers (HC) and patients with LAS, ARC and AIDS, were scre- ened for antibodies to: smooth muscle (SMA), nuclei (ANA), intermediate filame_n_ ts (IMF), microfilaments (MP) (IFL on rat kidney and HEp-2 cells, 1:40 serum d_i_ lution) and extractable nuclear antigens (ENA) (CIE, undiluted serum). HC(15) LAS(28) ARC(13) AIDS(8) tot.(6/¢) SMA 3(201) 7(252) 7(542) 5(632) 22(342) ANA 4(272) 9(321) 4(312) 1(132) 18(281) anti IMF 3(202) 6(212) 5(382) 3(381) 17(271) anti MF and anti ENA 0 0 O 0 0 SMA positivity showed always the V pattern and was associated with anti IMF (p< 0.01). The number of circulating CD4 lymphocytes was higher in SMA+ than SMA- AIDS patients (p<0.05). The autoantibodies status did not correlate with: ciru_: lating platelets and immune complexes, serum gammaglobulins, cutaneous anergy. Serum non organ specific autoantibodies do occur in HIV infected patients with the same pattern (SMAV with anti IMF reactivity) of other viral infections. Itis not known whether HIV itself can trigger the process. The SMA prevalence increa- ses with the disease progression. 112113 mammal or n/or+ Inflow+ 434? CD4+ 21-3?me armors nu— Rm; 1H5 svcwmn or HIV manor-1m. Raise 12., cum r.n.,-Scmatm H.L.','Casertan M.G.','Rllsatelli LW r4. Infect.Dis.md Imrrpafinl.an.—'Clinica1 Pathol.,0m. Womfiologantaly The pmgrostic meaning of o/nr*m+,m4*4sa+.m4+am+ 1W subsets am the evolutim of HIV infection vas investigated in the followim abjecm: 13 l-IIV—Abpoeitivemly, 48m, fimflsAflSwimHmlmcystiscarmiinle— Imus. Innoclmal mtibcdiesmae applied by Coulter Irmnlcgy aid Becbcn Dic kirsm‘a'mi were used with the Coulter lysim pmoedne. nail-color flow cytane— tr'ic malyses were performed with mars V. In 4the patients (pts) HIV—Ab positive it was mmted a decrease mlycl’fle CD4 434 sheet (388F150/m1 w n.v. SSW/m1: p<0.01).1!Ec-redntlmvm none re— mrkflfle in the further sms: 1A5 3436-197/ml (“0.01), AK: 2783:218/m1 (p<0.fll) AIns 34:25 (prom). The (104*er Wrocytes were decreased in ABC, 1m45/m1 vs n.v. mes/m (p<0.01) and anus sum/nu (p400 l3 21 66 418 Skin test reactivity remains stable down to T4 counts of 300, with a sharp decline in reactivity observed at counts below 200. Nevertheless, great individual variability is seen with 27% of HIV seropositive patients with T4 counts less than 100 still able to mount some skin test reactivity. TP136 EVIDENCE OF HUMAN IMMUNODEFICIENCY VIRUS ENCEPHALOPATHY IN THE ABSENCE OF OVERT NEUROLOGICAI. DISEASE JOSEPH R. BERGER, MARGARET FISCHL, LIONEL RESNICK, RICHARD DIX, WADE PARKS, University of Miami School of Medicine, Departments of Neurology, Internal Medicine and Microbiology, Miami, Florida. Twenty five HIV seropositive, male homosexuals with AIDS related complex (16) or AIDS (PCP within 90 days)(9) had neurological assessment upon entry into an antiviral protocol which excluded patients with overt CNS disease. Review of systems revealed complaints of memory loss and poor concentration (11), peripheral paresthesias (5), headaches (4), altered mood (0). and hallucinations (l). Abnormal recent memory and trail making tests were noted in 9 and 12 patients, respectivel Examination revealed a pathologically brisk jaw jerk and/or frontal release signs (13? hyperreflexia or asymmetric reflexes (l2), postural tremor (l0), incoordination (4) and diminished distal sensation (3). The neurological assessment was completely normal' 1n only '6 patients- CT scan revealed cortical atrophy 1n ll/G. MRI demonstrated diffuse hyperintense white matter lesions on T2 weighted' 1mages in 33/11. CSF examination in 16 patients disclosed a mononuclear pleocytosis (6-200 cells/mm 3) in 6, increased protein (116-79 mg96) in 7, and glucose 60 mg% in l2. CSF HIV cultures were positive in 0/7. Intrathecal synthesis of HIV specific IgG was detected in 11/10. All 1!: had antibody to spill, whereas only 6 had antibody to p210. No herpes viruses, adenoviruses or enterovlruses were isolated from the CSF. Evidence of an underlying HIV encephalopathy in ARC and AIDS in the absence of readily identifiable neurological disease is extremely common. Over 80% exhibited abnormal neurological findings and 7896 had intrathecal antibody synthesis to HIV. CSF studies and neuroimaging complemented the neurological examination in confirming the presence of HIV-related CNS abnormalities. T3131 Clinical Features of Transfusion-Associated Human Inmunodeficiency Virus (HIV) Infections in Children. JOSEPH A. CHURCH, Childrens Hospital of Los Angeles and USC School of Medicine, Los Angeles, CA, USA. Blood transfusion (tx) represents the risk factor in over 50% of HIV patients (pts) at Childrens Hospital of Los Angeles (CHLA). 0f 17 pts (15 M, 2 F) with AIDS or documented HIV infection acquired through blood transfusions, 10 had AIDS, 5 AIDS-related disorders and 2 were asymptomatic. Ages at diagnosis (Dx) varied from 8 months to 41 years (nean 3.7 years). Ten pts (9 M, 1 F) received Tx as premature infants; 5 other symptomatic pts (4 M, 1 F) received Tx at 2 days to 6 years of age. The 10 pts infected as prematures were compared to the 5 other symptomatic pts transfused later The time (in years) from Tx to development of symptoms (Sx) was 1.6 for pre- matures and 1.7 for the others, from Tx to Dx of AIDS or HIV infection was 2.7 and 2.8, respectively; and from first Sx to Dx 1.2 and 1.2, respectively. Failure to thrive, chronic oral candidiasis and hepatomegaly were seen in both groups. Recurrent or persistent otitis media or sinusitis was seen in 9 of the prematures and 2 of the others. Interstitial pneumonias including P. carinii, lymphoid interstitial pneumonitis and pulmonary fibrosis were seen in 8 prematures and only 1 of the other pts. Four of 10 pts infected as pre- matures have died; 1 of 5 pts infected later has died. In sunmary, Tx-associated HIV infection in premature infants was no more aggressive than that seen in pts transfused at older ages. The high prevalence of interstitial pulmonary disease in post-prematures may reflect microanatomic damage and/or local host defense disruption associated with the respiratory distress syndrome seen in these pts. 85 TP138 Diagnosis and Investigation of Hairy Leukoplakia Using Non-Invasive Techniques 3.5. GREENSPAN*, D. GREENSPAN*, Y. DE SOUZA", and U.K. FREESE**, *University of California, San Francisco, CA, and **Deutsches Krebsforschungs- zentrum, Heidelberg, FRG. A high proportion of HIV seropositive individuals with oral hairy leukoplakia (HL) subsequently develop AIDS. Diagnosis of oral hairy leukoplakia currently requires biopsy, a procedure which may not be readily available or may be contraindicated, for example in he mophiliacs. We have investigated the use of two non-invasive techniques directed towards establishing the presence of EBV in the epithelial cells of HL lesions. Filter in-situ hybridization (FISH) involved the use of the pBngU probe for the lR-l sequence of EBV, hybridized to cells obtained from smears applied to filters under suction, and visualized autoradiographically. Cytospin in-situ hybridization (ClSH) involved the same probe, used on cells applied to glass slides by cytocentrifugation and visualized using a multistep biotin-enzyme technique. Twenty cases of biopsy-confirmed HL were studied to compare the ease and accuracy of FISH and CISH. Both techniques showed the presence of EBV-DNA in all cases. FISH showed very high sensitivity but was technically more demanding and involves the use of radioisotopes. CISH allowed identification of single positive cells, was quick and relatively simple. Both techniques permit confirmation of EBV infection in HL with high accuracy and may obviate the need for biopsy in some cases. Supported by the University of California Systemwide Task Force on AIDS and by the Deutsche Forschungsgemeinschaft. “3139 Evaluation of a Clinical Case Definition of Pediatric AIDS in Africa. ROBHU‘ L_. COLEBUNDERS’l, A. mRG**, P. NGUYEN- DINH"", K. NDOK0"**, I. LEBUG—HE", F. PIOT"" et al. * Projet SIDA, Kinshasa, Zaire, M CDC, Atlanta, "1 Mama Yemo Hospital, Kinshasa. "M Institute of Tropical Medicine, Antwerp, Belgium. To determine the accuracy of the clinical case definition for AIDS in children which was proposed at the second meeting of the WHO collaborating centers of AIDS December 1985, we examined and carried out HIV serology on all 155 children hospitalized at Mama Yemo Hospital between July 5 to 7, 1986. Nineteen (129s) of the 155 children examined were HIV(+). Symptoms and signs signifiantly associated with HIV seropositivity included: diarrhea lasting for at least one month, chronic or recurrent otitis (p=. 03), generalized lymphadenopathy (p=. 007), oral candidiasis (p=. 03), hepatomegaly (p-. 03) and splenomegaly (p=. 02). Illness of the mother (p .0001) and presence of HIV associated symptoms or signs in the mother (p-.0001) were also strongly associated with HIV seropositivity. The provisional mo clinical case definition of pediatric AIDS was found to have a specificity of 88 t, a sensitivity of 40%, and a positive predictive value for HIV infection of 30%. Our study suggests that the use of the proposed Win pediatric clinical case definition for surveillance of AIDS in African children will result in significant underreporting. Rinflil SamyNazceathyc (II-EN) in Putiettswiflim TP140 mvm R. mm m,* 11.15. m,“ J.w. mm,* and anaroimtsof ,meJdn-sxfizidmmiversitysdml ofl/bdscire, 131mm. Paresthsiasani dysesflasiasomfixadhothefatammsynptminpatim mflnpre-tmniralsmdmflmisclirflmlpicumhasbemcanedffltdm minedanlde . y,mlsaiecxy mat-sail: msamremminarpliuneinmmmlmwedaplimieswereahsatm Zardredwedms.'nueedainsuatedcmralnnale1trapmts,mflmmrsasmy typiixlofadistalainwafliy. Inaretrmpaxivesunyofhmsamqasies,uepre1dnalyzqaortedfumnai wiflisevezedegamudmofflegncilatmctafthesdmludmetal, Ann NSIKOISBG, 20:146). mdevelcpedptmfimmdiSCalpuesfl-miasam weal-hams, midiirmeaedinswed ' ammdhiialmfifiyaiologialpicumofflammlpatimmflsm ' otuielsiasinfiiegzacileuwtin4otlarpatdsmmth synptmsostygestaa'seMbadé'L-xwofflnmmy mm.Tni.s nayrfiresenta adegamatiminfiadzsalmotgarglimcans, pmaihlyfiundjzect HIV 331m. TUESDAY, JUNE 2 TB 141 LIONEL RESNICK, S. NORMAN, M. SHAUKAT, K. NAV, J. HERBST, M. COHN, et al., Mount Sinai Medical Center, Miami Beach, FL. HIV infection is associated with neurologic disease. Data on sleep are scarce and suggest that subjective complaints of initiating or maintaining sleep are secondary to anxiety or depression. No polysomnographic data ex- ploring sleep architecture in HIV infected individuals exists. A pilot study was conducted to evaluate sleep physiology in asymptomatic HIV seropositive patients. Eight HIV seropositive (western blot analysis)homo— sexual males (mean age of 37.6 years) (Group A) and 3 HIV seronegative homo- sexual men (mean age 28 years) (Group 3) volunteered to complete a sleep his- tory questionnaire and a polysomnogram (PSG). Both groups did not differ in their sexual practices or lifestyles. Two patients in Group A and none in Group B had sleep complaints,i.e. sleep onset and maintenance difficulty and daytime fatigue. Mean sleep efficiency index was less in Group A indicating a poorer quality of sleep (mean 87%,range 71-96%) compared to Group B (mean 94%, range 90-96%). Six of 8 Group A patients had above normal predicted percent slow wave sleep (%SWS) (mean 21.8%,range 16-32%),whereas this occurred in only 1 Group B patient. Also,%SwS in the second half of the night in Group A (mean 12.7%,range 2.2-25.l%) was greater than Group B (mean 5.3%,range 0-8.9%). Ne hypothesize that sleep disturbances can be caused by altered biological processes and not just psychological factors. Early alterations in sleep architecture may be an early marker of CNS involvement in HIV infected patients. Alterations in Sleep Architecture in Asymptomatic HIV Seropositive tients TP142 Is Cytomegalovirus (CMV) a cause of pneumonia in AIDS ? ' DANIEL VITTECOQ, S. DURAND, MC. HAZERON, A. HIRSCH, Y. PEROL, St. Louis Hospital, Paris, France. In order to investigate the incidence of CMV (frequency and prognosis) in the lungs of AIDS patients we examinated broncho alveolar lavage (BAL) fluid in 80 AIDS and 20 preAIDS patients observed during 14 months. DAL was performed either for pulmonary symptoms or unexplained fever ()3 weeks). CMV was isolated by culture in 29 patients (32 EAL) and was the only microbiological agent in 14 DAL, and was associated with other agents in 18 BAL (1A Pneumocystis, 3 Hycobacterium avium intra cellulare (HA1), 1 Cryptococcus neoformans). 2 preAlDS patients had CHV in BAL and AIDS was diagnosed 6 months later in l of them admitted for an unexplained fever which was due to pericardial tuberculosis. CHV was observed in 13 AIDS having had at least one opportunistic infection (OI). It was also isolated in lb AIDS during the first OI. 5/29 patients with CHV died of the pneumonia which required EAL, but no death seems to be specifically linked to CMV, since another agent was found in these cases: Pneumocystis (3), MA! (2) associated in 3 cases to pulmonary kaposi sarcoma. No patient died of pneumonia when CMV was the only microbiological agent. CMV is frequently isolated in BAL during AIDS (30!). isolated more often in advanced stages of the disease. significance of CHV is unclear in this disease. CHV seems to be The pathogenic “3143 Increased Risk of cervical and/or Vaginal Sgnnous Atypia in women ' Infected with HIV. LEWISMIGiFRIm, RSKLEIIN, DMALDE; KSGIREIEER, across. etal. Mmteficre Medical Guitar, Albat Einstein (bllege of Medicine, m, NY, use. Westmiedwoimwimnmsawellasfanalesexual porters(sm)ofnualeAms patients to determine the [xevalerne of cervical and/or vaginal missus atypia ad its relationship to HIV infection. sibjects mderwent standardized interviews regarding demographics and satual histcxy, couplets physical exams including pelvic exam, aidassayforHIVserummtibodiesafl'Mcellmm Sempleeofca'vical epithelimn fa: qtologic evaluatim were obtained and read by use cytopattnlogist blimhd to tiesioject'sl-IIVststus. 35mmtibody+(HIV+)mnm(28 933137 with AIDS) and 23 without HIV infection (I-lIV—) (all see) were evaluated. 11/35 (31%) HIV+ objects hai evidmce of sqzamom atypia compared with 1/23 (4%) of HIV- women (M219).- oampered to HIV- womm, HIV+ women had a significmtly increased harmony of veereal disease, decreased we of barrier cmlz‘aceptiwe aid fewer mmths since last sexual omtact with m NIB patient (you). also had significantly loser absolute T4 combs. HIV-l- women with atypia conpared to HIV+ woman witl'mt atypia had no simificmt diffema'ms with respect to my :hmograpiic, sexual or immunologic variables, except for mom mild-ea amng those with atypia (pow). We concllxle that HIV+ worm have a signifiomtly increased prevalence of cervical md/orvagfiulsqtamatypiacangmedblfiV—mhflnlflflgmipatypiawes not associated with variaflee relating to serial experience Hypotheses to explain the findings incluie increased mptibility of HIV+ womm to agate which may potentially promote cervical or vaginal atypda (e4. ppillomavirm), a direct effect of HIV infectim, m- increaaed mptibility of women with peexietent atypia to HIV infection. Additional epichmiologic, petlnlogic and virologic studies are required to explore these possibilities. HIV+ Home: 86 TP144 Failure to Maintain Normal Growth Pattern in Pediatric Hemophilia: ' Possible Predictor of Progressive Immunodeficiency. DQBEEN B. BBEIILEB‘ A.D. Forsberg“, P.H. Levine“, F.E. Brewster", C. Andrews“, J.L. Sullivan”. *Worcester Memorial Hospital and "University of Massachusetts Medical School, Worcester MA, U.S.A. Standard growth charts and clinical, serologic and immunologic measurements were carried out over 3 years (1983—85) on a cohort of 37 HIV-antibody positive hemophiliacs, aged 2-15. Seven patients (group A) failed to maintain a normal growth curve for at least 2 years, while 30 (group B) grew normally. The mean ages of group A and B were 11.5 years (range 2.8-15) and 8.1 years (range 2.5-1'4.9) respectively. All had previously used non-heat-treated concentrate and were HIV antibody positive by 1984. There was no significant difference between the amount of factor concentrate utilized by each group. In 1983 there was no significant difference between the 2 groups in any of the immunologic or clinical parameters studied. By 1985 those who had failed to maintain a normal growth pattern had developed: 1) a significant decrease in the number and percentage of absolute T helper cells: 253/ul vs 813/ul, p<.01; 16.8% vs 30.11%, p<.01; 2) a decreased T helper/suppressor ratio: .37 vs .86, p<.01; and 3) decreased skin test reactivity. One patient who failed to grow has developed AIDS and 1 patient has had chronic diarrhea and weight loss; another has persistent oral candidiasis and recent severe weight loss. No patient in the control group is ill. Since those who failed to maintain a normal growth pattern exhibited signlficantly greater deterioration in immune studies than those who continued to grow and since cessation of normal growth often preceded laboratory or clinical deterioration, it is possible that a period of lack of growth could be predictive of more severe progression of clinical manifestations in children with HIV infection. It is also likely that growth failure is another sign of clinically symptomatic HIV infection in children. I TE145 Evaluation of the WHO Case Definition of AIDS in Rural Zaire. KEVIN E; 2g COCK, R. COLEBUNDERS, N. NZILAHBI, H. FRANCIS, P. PIOT, 3.8. MCCORMICK, at al. Division of Viral Diseases. Centers for Disease Control, Atlanta, GA, U.S.A.; Project SIDA, Kinshasa, Zaire; Institute of Tropical Medicine, Antwerp, Belgium. The World Health Organization (HHO) has proposed a clinical case definition for AIDS for use in areas where medical facilities are inadequate to confirm AIDS as defined by the Centers For Disease Control. In these areas the clinical definition can only be evaluated against human immunodeficiency virus (HIV) antibody status; this evaluation is therefore one of the case definition as an indication of symptomatic HIV infection. Seventyoseven patients in A rural hospitals in the Equateur Province of Zaire were examined and had ssrs tested for anti-HIV. Fulfillment of the clinical criteria was compared with anti—HIV status. Twenty-one (271) patients were anti—HIV seropositive, and 22 (291) fulfilled the criteria. For diagnosing symptomatic HIV infection, the HBO criteria performed as follows: sensitivity 52!; specificity 80%; positive predictive value 501; negative predictive value 821. The clinical spectrum of HIV infection is broad, and determining the amount of HIV related disease and deaths is more relevant in Africa than strictly defining AIDS. we propose the case definition be assessed accordingly. TP146 Wtion of Neurodevelopmtal Ootoune in Cmgaiital HIV Infection: Heterosemal vs. IVDA Transmissicu E w.Dianmfl*,A.L.Belnan**,A.A.Wiznia,J. Kasmgin,H.J.Cohen*,A.Rabinstein. Albert Einstein College of Medicine,Deparment of Pediatrics,*Rose Kennedy Center, Bronx, N.Y., *‘SJNY, Stony Brook, N.Y. Previously described murodeveloprental flipairment in infants and chil- dren with AIDS includes a variety of cognitive deficits, motor delay, enceph- alopathy, acquired microoephaly, spasticity and dementia. Most cases of con- gemitalAIDStodatehavebeentracedtomatemalIVdmgabuse. Drugabuse during pregnancy is associated with greater fetal wastage arr! less favorable neurodevelopnental mtcme in the newborn. A pilot study for a long tam multidisciplinary prospective project was corrimted to delineate those per— nicious morodevelopmtal effects which were disease induced and those drug indwed sixteen HIV-antibody positive pediatric patients under the age of 215 years were exanu‘ned by raters blind to the etiology of the infection, using standardized cognitive treasures and Immological assessment. A grwp of 10 waretheoffspuringofcmfimedmaternalwdnigabmers; anotherGwemein— fected in utero fmn heteroseamal contact. Statistical analysis using the Fisher erect test slowed no significant difference between the 2 groups on either the neurological or cognitive (Bayley EDI scale) neasum. Earlier onset of CNS synptms was associated thhapoorerlmgteundeveloprentalpzogrnsisamahigherscoremthe AIDS Wthy rating scale for related dystorphic features. Lack of significant differences hem the gmipssuggests how severely the HIV infection affects the developing neuron systan regardless of acposure to other potentially taidc environmental factors. TUESDAY, JUNE 2 112141 Diarrhea in Patients with AIDS/ARC. SAUL J. RODRIGUEZ, M.M. HERNANDEZ, K.V.I. ROLSTON. Immunological Disorders and U.T.S.C.C. M.D. Anderson Hospital Institute, Houston, Texas. U.S.A. Diarrhea is a cannon problem in patients with ARC and AIDS. Much time and effort is spent in evaluating these patients. We examined the records of 230 HIV antibody positive (53% AIDS; 47% ARC) patients. Of these, 64 (28%) had diarrhea and 63 were male homosexuals. Conventional work-up (stool smears and culture, ova and parasites, mycobacterial smear and culture, and viral culture) revealed causative organism(s) in 19 patients (29%). Eleven patients had infection with one and 8 with more than one or anism. Thirteen different pathogens were recovered including Cryptosporidia (5), Giardia and CMV (4), Shigella flexneri (3), Entameba coli and Entameba hartmani (3), Isospora belli, Blastocystis hominis, E. histolytica, Salmonella typhi, Camphylobacter spp., and Pseudomonas putrefaciens (l). Seventeen of these l9 patients received specific therapy with ll complete and 4 partial responses. 0f the remaining 45 patients 22 (49%) had self—limited disease which required no therapy. Fifteen of these had ARC. Twelve others responded completely and 6 partially to non-specific anti-diarrhal agents (Imodium, lomotil). Only 5 patients had persistent diarrhea requiring further evaluation. Endoscopy and intestinal biopsy was diagnostic in 3 of 5 patients. Our data suggest that the majority of ARC/AIDS patients do not require endoscopy and intestinal biopsy for the evaluation of diarrhea since it is often self-limited or may reSpond to non-specific therapy. Institute for and Tumor T2148 Renal Tubular Nephropathy in AIDS Causing Volume Depletion and Mel- nutrition. £;KJ_MAESAKA, A.J. CUSANO, F.P. SIEGAL, H.L. THIES, L.I. Jewish Medical Center, New Hyde Park, N.Y. Height loss and cachexia often accompany AlDS.We did renal clearance studies in 4 patients with AIDS,wt loss,cachexia and clear evidence of severe hypovol— emis(postural hypotension,reflex tachycardia,high plasma renin and ADH levels, cvp 0),but no evident fluid losses. Renal tubular defects were shown in all pts by high renal excretion rates(RER) of uric acid(UA) and various amino acids(AA) despite low blood levels and volume depletion. Salt therapy did not correct vol- ume depletion,but further increased RER of UA and AA,and showed abnormal RER for sodium,potassium and phosphorus. Also,one pt returned to baseline volume depleted state when extra salt was stopped. These data highlight the magnitude of the tubular defects since similarly volume depleted pts with normal tubular function markedly reduce RER and retain augmented salt intake. All pts had n1 creatinine,urinalysis(no protein,glucose) and adrenal function. Opportunistic illnesses or drugs did not cause these effects. Conclusion: HIV infection ap- pears to cause renal tubular defects which produce severe hypovolemia due to renal salt wasting,and also significant renal losses of other minerals and amino acids that worsen when replacing salt. Low plasma AA resulting from renal losses may partially account for the cachexia in AIDS. Salt therapy to replete volume given without other nutrients will aggravate malnutrition by increasing renal losses of amino acids and other nutrients. TR149 Distribution of HIV Message in Postmortem Brain THOMAS A; ESKIN and M. H. STOLER, Department of Pathology, Uni- versity of Rochester, Rochester, NY, U.S.A. The in situ hybridization technique has the potential for al- lowing very precise localization of the replicating human immuno- deficiency virus (HIV) in the brains of AIDS patients who suffer from neurologic complications. We preliminarily tested the util- ity of this approach as applied to routinely fixed and processed tissues [Stoler et a1 (1986) JAMA 256: 2360] and here report ad- ditional studies of similarly processed brain tissue from autop— sied AIDS patients. In this study we examined cases with, and cases without typical histopathological evidence of "AIDS enceph- alitis". but in either case with additional ongoing or potential complicating CNS pathology (eg. primary CNS lymphoma, systemic CMV infection). Our conclusions are: (1) that HIV can replicate in brain concurrently with other complicating CNS processes and (2) i_n situ hybridization applied to routinely processed autopsy (as well as surgical) tissue, provides the potential for direct study of the topographic distribution of HIV infection in brain, for correlation with specific neurologic impairment in life. 87 T3150 Prognostic Indicators of Survival in AIDS Patients with Pneumocystis carinii Pneumonia: A Biostatistical Analysis N.A. LEE*, E. EELEIN*, L. FRAULINO+, WARREN A. ANDIMAN*+. *Yale University School of Medicine, +Yale-New Haven Hospita , ew aven, CT. In order to identify prognostic indicators of survival from Pneumocystis carinii pneumonia (PCP) we studied retrospectively our first 48 adult AIDS pa- tients with PCP. We determined which clinical and laboratory features present early in the course of treatment were predictive of prolonged survival from an initial episode of PCP. Statistical evaluation of uncensored (followed to death) and censored (followed to date last seen) patients was accomplished using the survival analysis method of Kaplan and Meier. The Cox-Mantel test was used to determine whether the difference between separate Kaplan and Meier survival curves was significant. Seven variables emerged as significantly associated with prolonged survival: an initial positive response to therapy, the presence of night sweats, a normal or near-normal chest Xray, an arterial oxygen tension ’SOmm Hg in room air, a TH/TS ratio’0.25, either no alteration of PCP therapy or alteration because of adverse reaction only and the absence of respiratory failure requiring artifi- cial ventilatory support. The singlemost important indicator was the patient's initial response to anti-PCP therapy and emphasizes the importance of the clin- ician's assessment during the first 7 days in estimating the ultimate length of survival. The presence of dyspnea on exertion and significant recent weight loss, a re- spiratory rate >30/min, fever, and a widened A-a gradient were associated with a general reduction in survival. Familiarity with specific indicators of survival from PCP assists the physi- cian in providing realistic information to the patient and his/her family re- garding prognosis and guides decisions about future care. “3151 Neuromuscular Complications of Human Immunodeficiency Virus (HIV) ' Wt, G.H. PEZESHKPOUR**, J.L. SEVER*, *NINCDS, NIH, Bethesda, MD., **Armed Forces Institute of Pathology, Washington,DC. We have seen the following neuromuscular complications in patients infected with HIV: I. Perimeral Neuropgthles of the following subtms: 3) Acute demyelinating inflammatory sensorimotor polyneuropathies identical in presentation and course to Guillajn-Barre syndrome with occasional cytomegalovirus (CMV) inclusions in the Schwann cells; b) Mononeuropathy multiplex which can remit spontaneously or evolve Into a distal symmetric polyneuropathy; c) Chronic, slowly progresive sensorimotor demyelinating polyneuropathy with CSF pleocytosis and elevated protein; d) Small fiber, distal, symmetric sensory neuropathy, due to a distal axonopathy; and e) Large fiber sensory ataxia neuropathy due to ganglioneuronitis. Nerve biopsy shows demyelinatlon with inflammatory infiltrates (la, 1c), vasculltis (lb), axonal loss (Id), inflammation in the ganglia (la), or a combination of findings. Polmyositis as described (Dalakas et al. JAMA, 1986). Type II mode fiber atroay, as the only morphological finding in the weak muscles due to poor nutrition, rapid weight loss or remote effet of lymphomas. IV. Am otro ic Lateral Sclerosis (ALS) in one case. Although some neuropathies and the type II atrophy can be due to nutritional factors, there is evidence that the majority of the cases are due to HIV infection, co-lnfection with other viruses, i.e. CMV or due to immunopathologic mechanisms. Based on our experienoe, a neuromuscular disease may be the presenting sign of an ARC or developing AIDS or the only clinical manifestation of HIV seroconversion. Patients at risk who present with neuropathy or myopathy, should therefore be screened for HIV. II. III. TP152 The Control oI HIV Transmission - A Public Health Challenge R uiring Ihe Maximum 01 Foresight, Courage and Reassessment and Flseglbilhy. , Centers for Disease Control, Berkeley, CA 1 IS c ear that, ause mosI (>90% HIV transmission in the United States is through behawor that can be modiiie , HIV transmIsSIon can be controlled. The marked behavior changes of San Francisco homosexual men and the resulting decreased lnlection rates attest to the potential success of behavior modification. Yet. despite some local successes by-and-Iar e our_ AIDS revenIion eflons are IaIIing. W y? FII'SI, our political, budgetary, a publlC heali managerial s stems are not geared to such long term emergencies and, as a result, have large y been paral zed by the day-Io-day chaos of A 08. Second, we as a society have not deve oped t e courage to move ahead with the difficult issues involved with fielding an AIDS prevention program. With recent publications (Surgeon General's Report, NAS Repon, Francis and Chin) there are prevemvon plans around which local programs can be designed. The message to be promul ated by these programs is rather simple: Dangerous vims - take personal responsu Ilhy Io protect yourself: 1) If you are going to have sex, use a condom. 2) Don't use drugs; if you must. don't share unsterllized needles/syringes. 3) If you are goung'io get pr nam and possmly have been exposed. be tested before and II you are posnwe. don't ecome pr nant. In the absence of efiectlve vaocmes an era utic agents. the extent cl 5 read of HIV VVI" be determined by the eflecuveness o changing aI—risk behavior. T at shocilveness will require an Immense shon term "catch‘up' program oI adult education, motivation and skill bmlding Iollowed by ”maimenance" programs through schools and aduh updates. In addition. prevention centers where indivuduals and Iamllles canllnd Inlormaiion. testing. and su rI groups will be increasi ly Important. Finally, assessment by enodlcal y determining prevalence an incidence oI Infection, behawor changes a STD rates will be crime In evaluating the success or (allure of the program so that appropriate changes can be Instituied. TUESDAY, JUNE 2 TR153 HIV—1 and 2 are present in Ivory Coast in AIDS patients A. OUATTARA*, GROUPE IVOIRIEN DE TRAVAIL SUR LE SIDA*, M. A. REY“, F. BRUN-VEZINET**, G. DE-THE*** — *Pasteur Institute, Abidjan, Ivory Coast **Hopital Claude Bernard, Paris, France ***CNRS Laboratory, Fac Med A. Carrel, Lyon, France Investigation of AIDS in Ivory Coast showed that the disease became clinically evident by the end of 1985 and took epidemic proportions in 1986. Sera collected in June I986 from patients with AIDS, according to the WHO Bangui definition, showed in 30 % of the cases antibodies to HIVvl alone, in 20 % antibodies to HIV-2 and in 50 % antibodies to both HIV-1 and HIV-2 env and gag antigens. Sera considered as HIV-2 positive exhibited however weak and variable cross reactivities to HIV—l gag products (P18, p26, p55). Survey of prostitutes in Abidjan showed that about half of them had antibodies to both HIV-1 and 2. These results indicate that both viruses are present in Ivory Coast, that they are associated with AIDS and that infection by one HIV strain does not protect from the other. Prior sera-epidemiological investigation (Ouattara et al, Ann. Inst. Pasteur (Virology), 1986, 137E: 303-310) showed a low prevalence of infection by HIV-1 in the general population of northern, eastern, western and southern regions of Ivory Coast in mid—1985. Prevalence of HIV-2 antibodies in these sera is being investigated. TP154 Limited Value of Mycobacterial Smears in the Diagnosis ' of Pulmonary Tuberculosis in AIDS/ARC Patients. NATALIE C. KLEIN*, F.P. DUNCANSON*, T.H. LENOX*, R. VOGEL*, S. BAILEY*, G.P. WORMSER**, *Metropolitan Hospital Center, **New York Medical College, New York City., New York, and Valhalla, New York, U.S.A. Tuberculosis (TB) is increasing in incidence in certain geogra- phic areas where both TB and HIV infections are endemic. Prior studies have emphasized the presence of extrapulmonary disease in patients with both infections. Less well known is the fact that the majority of such patients have pulmonary TB as a component of multisystem tuberculous infection. We reviewed our experience with TB diagnosed by culture over a two year period from January 1, 1985 to December 31, 1986 at a metropolitan hospital in New York City serving East and Central Harlem and the South Bronx. Over this time period 104 hospitalized patients had pulmonary TB. Of these, 33 (32%) were known to have or develop AIDS (11) or ARC (22). Of these 33 patients 94% were male. of the 71 patients with pulmonary TB without AIDS or ARc, 75% were male. Myco— bacterial smears of pulmonary secretions were significantly less frequently positive in AIDS/ARC patients 16/33 (48%) (mean 2.5 sputum smears examined/patient range 1 to 9) compared to 54/71 (76%) in patients without AIDS/ARC (P <: -05). We conclude that about one third of pulmonary TB patients in certain areas of New York City have AIDS/ARC. The diagnosis of pulmonary TB should not be excluded on the basis of negative sputum smears. Empiric anti—TB treatment is warranted when TB is suspected in the AIDS/ARC patients pending culture results. TR155 AIDS-associated Kaposi's Sarcoma: Antiproliferative Ef- fect of Recombinant Interferon Alpha. PETER KERN*, W. MEIGEL**, T. DETTKE**, M. DIETRICH*, *Bernhard— Nocht—Institut, Hamburg, Germany, **Allgemeines Krankenhaus St. Georq, Hamburg, Germany. Twenty-eight patients with biopsy—proven Kaposi's sarcoma were treated with interferon alpha 2a. Daily intramuscular injections of 18x 106 Units were given for 3 months, followed by 3—weekly administrations subsequently. Staging of patients was performed according to the Walter Reed classification: the number of pa— tients is given in brackets: NR1 (0), WRZ (6), NR} (3), NRA (4), wR5 (11), and WR6 (A). Response to treatment was judged in month— ly intervals. An antiproliferative effect of interferon was ob- served in 9 patients (32%) during the first 3 months of IFN sub- stitution and remained so for at least 6—9 months. The median ob- servation time of the responder group was 11.5 months. Three pa— tients died 11, 15, 17 months after start of treatment due to op— portunistic infections or tumor progression. All of them had a less favorable score in the WR classification (wRB—SL Theimjorfly of patients in the nonresponder group had a higher WR score (wRZ (l), NR4 (4% MR 5 (10L WR6 (A)). Most patients suffered from re— peated episodes of opportunistic infections. Seven out of 18 died, the mafian observation period was 6 months, ranging from 2 to 18. Some patients achieved stabilization by the combined treatment of IFN together with vinblastin. Thus, patients with Kaposi's sarcoma and HIV infection classified according to HR into stage 2 or 3 may have a favorable response to interferon alpha 2a. 88 TP156 Asymptomatic Myositis in HIV Antibody-positive lien WILLIAM O. HARRISN, S.W. BM, C.M. autumn, United States Naval Hospital, San Diego, ca. Anong the first 500 active-dity naval personnel idt-mtified as HIV anti- body-positive and evaluated at the Naval Hospital, San Diego, 17 vere noted to have creatine pneplnkinaae (CPR) levels nore than 50% above the normal range for the hospital laboratory. All were asynptamtic with regard to msculoskeletal goblens. After bed rest 4 of these individuals continued to have markedly elevated aizyne levels. CPK isoenzyne detennination was 100% in (skeletal muscle—related) in each ass. macle strength testing and electranyography were nomal in 3 nan. muscle biopsies of 3 of the 4 slated acute nyositis. mly me of the 4 developed ABS. His wositis regressed during treatment for RIP but recurred when his pieunnnia recurred. M otherswereinDoDmalterReed) Classlamithethirdinclass 3.T'hese3 have remained well, with persistent mderate—to—uarked CPR elevations. A recent pper reports acute symptcuatic polymyositis in association with AIIS. It further implies that the use of steroids as therapy for nyositis nayenhamethemsetofiAnS.WegxesentUieseasesasmequoeiteaflof what nay be a spectrum of HIV-associated wositis. (ally one of the 4 developed AIDS. He was not treated with steroids, Int eventually died of A115. The remaining 3 shod no evidence of progressive HIV-associated disease. mirther study will be necessary to confirm an association between HIV and nyositis in asymptomatic antibody—positive individuals. TR151 The cerebrospinal fluid diagnosis of HIV-encephalitis WILFRIED LUER*, W. BUTTNER? S. POSER*, D. EICHENLAUB**, H.D. POHLE**, K. Felgenhauer*, * Georg—August Universitat thtin- gen, ** Rudolf-virchow Krankenhaus Berlin, Federal Republic of Germany In order to establish a reliable procedure for the early diagno— sis of HIV—encephalitis, 56 patients — 15 HIV-antibody positive, 10 with ARC and 31 with AIDS - were examined with the following methods that have been recently developed to evaluate the humoral immune response within the central nervous system: - the quantitation of the locally produced immunoglobulin fractions in CSF (IgG, IgA and IgM) by an empirical differentation diagram. — the comparative quantitation of HIV—specific antibody activity in CSF ans serum by a modified ELISA based on identical IgG—con- centrations. This method avoids the calculation of indices and compensates impairments of the blood—CSF barrier. — the confirmative evaluation of the HIV—specific antibody spec- trum in CSF and serum by Western blot. A CSF/serum ratio of the specific antibody activity above 2 is strongly suggestive for an intrathecal HIV—antibody synthesis. According to this criteria 46 % (7/15) HIV—antibody positive patients showed intrathecal antibody synthesis indicative of a very early HIV—infection of the central nervous system, whereas 70 % (7/10) of the patients with ARC and 65 X (20/31) of the pa- tients with AIDS showed evidence for HIV—encephalitis. The local production of immunoglobulins, however, does not correlate to apparent neurological symptoms. T2158 Patterns of Magnetic Resonance Brain Scanning of Lesions in AIDS and ARC Patients. JERRV JARVIK, J. HESSELINK, C. KENNEDY, R. TESCHKE, C. WILEY, J.A. MCCUTCHAN et al., Unlverslty of Californla, San Diego, San Diego. CA. Magnetic resonance (MR) brain scans of 30 patlents with either acquired immunodeficiency syndrome (AIDS) or AIDS—related complex (ARC) were reviewed. Twenty patients had focally abnormal neurologlcal examinations at the time of scanning. Pathological diagnosis was available In nine. Four patterns of abnormality were observed on TZ-welghted 1mages. Multlple discrete high signal foci (Type A) were found In patients with toxoplasmosis and progres- sive multifocal leukoencephalopathy (PML). Large. bilateral patchy to con- fluent hlgh signal areas within the white matter (Type B) represented a white matter encephalitis secondary to cytomegalovirus (CMV) or human immunodeficiency virus (HIV). Generalized enlargement of the cortical sulci and ventricles (Type C) reflect atrophic changes probably from the chronic HIV infection. Solitary high signal intensity lesions (Type D) suggested a focal (VZV and coccidloidomycosls in our series) opportunistic infection. Differential diagnosis of brain abnormalities in patients with AIDS can be assisted by recognition of these characteristic patterns. TUESDAY, JUNE 2 '[R159 Central Nervous System Reactions to Trimethoprim-Sulfamethoxazoie in Acquired Immunodeficiency Syndrome (AIDS) Patients. MICHAEL J. BORUCKI, D.S. MATZKE, R.B. POLLARD, Division of Infectious Diseases, The University of Texas Medical Branch, Galveston, TX Adverse reactions to trimethoprim-sulfamethoxazole (TMP-SMZ) therapy, espe— cially leukopenia, thrombocytopenia, and rash, occur with increased frequency in patients with AIDS. Only one CNS reaction (seizures) to TMP/SMZ in this population has been reported. The CNS side effects of TMP—SMZ reported in nor- mals include headache, depression, and hallucinations. Three patients who had tremor as a prominent manifestation of TMP—SMZ therapy were observed in an 18- month period. One patient also developed hallucinations, another a wide-based gait and dysmetria. Two of the patients were noted to appear apathetic at the time of the reaction. Symptoms occurred 4-9 days after the onset of therapy and were co-incident with the development of leukopenia. All three patients had a mild hyponatremia (127-l30). The tremor. hyponatremia, and leukopenia resolved after discontinuance of the TMP-SMZ with marked neurologic improvement evident in the first 24 to 48 hours. During this same interval 27 additional AIDS patients were treated with TMP-SMZ for Pneumocystis carinii pneumonia, 25 of whom were treated with both Pentamidine and TMP-SMZ, either concurrently or sequentially. Laboratory investigations failed to implicate alternative eti- ologies for the tremor. This experience suggests that not unlike the increased incidence of other toxicities previously reported, neurotoxicity to TMP-SMZ may be more frequent in the AIDS population than is generally appreciated. TP160 RETINAL DREW IN Tom's: WEB RETINITIS. Dennis u. my, W.R. Freeman, 0.3. Henderly, W.L. Wan, NA. Rao, J.M. Leedom, et all. University of Southern California, Dos Angeles, CA USA. Despite the freqient occurrence of cytomegalovirus (CMV) retinitis in AIDS patients, associated retinal detachment has not been reported. We treated twenty-five patients with AIDS and CMV retinitis with ganciclovir. Each patient was treated initially with 2.5 mg/kg every 8 hours for 10-20 days (induction) and then was placed on a maintenance regimen of 5 mg/kg/day 5-7 days/week. Every patient showed evidence by is exam of regression of the retinitis after the initial induction dosing. Ten eyes of six patients developed retinal detach-next during maintenance ganciclovir treatment. Retinal detachments presumed clinically as acute, sudden loss of vision in the affec- ted eyes. Multiple breaks in areas of peripheral, healed, atrophic retina aooumted for the detachuents. All eight eyes undergoing surgery had exten- sive retinal detachments that were reattached with vitrectomy and silicone oil. In the fellow eye of one patient, laser treatment was used prophylacti— cally to wall off a peripheral patch of healed retinitis. Endoretinal biop- sies and culture were taken in five eyes; evidence of persistmt CHV was seen in two cases daplte concurrmt and clinically effective ganciclovir therapy. We mlude that retinal detachnmt is a frequent conplication of treated CMV retinitis. These detachments are often surgically correctable. Because of the propensity of these eyes to develop proliferative vitreoretinopathy, vitrectomy and the use of silicone oil may offer long-acting tarponade to the extensive areas containing retinal breaks as well as preventing potential future retinal breaks in zones of healed retinitis. The possible effective- ness of laser prophylaxis to surround areas of thin healed retina warrants further evaluation. TP161 Prevalence of hairy laikcplakia and oral candidiasi.s among HIV— ' infected Danish hemphiliacs. mm sander, J.RINDUM, E.SCH'EIBEL, J.J.PINDBORG, Royal Dental College, anartment of Oral Medicine & Oral Surgery and East Danish Henrphiliac Center, University Hosfital, Copenhagen, Denmark. Oral hairy laikcplakia (HL) and candidiasi.s oowr freqlently and early anong sercpos. homosexuals bat are largely undescribed among hencphiliacs. All known patients with severe henrphilia (90) in Eastern Denmark were invited for oral emmination. Seventyseven (85%) responded, and the oral examination was con- dlcted without knowledge of the HIV-antibody status. Of the 77 patients 42 (55%) were sercpos..0nly one had AIDS. Erythenatous (atrophic) oral candidiasis was found in 4 sermos. (10%) and in one seroneg. patient (3%). No cases of psaidomerrbranois candidiasis were seen. I-lL was found in 6 serqoos. patients (14%) and in no seroneg. patients. Amng the 6 HL patients 1 had AIDS with PCP and l non—diagnosed lung symptoms. The mean T—hdperfl—mppressor cell ratio of the HI. patients was 0.3 whereas the same ratio was 1.0 for the 36 seropos.9non—HL patiengs (p=0.0013). The mean runber of T—helper cells was 0.2 x 10 and 0.8 x 10 among the HL and non—HI. sercpos. patients, re$ective1y q>=0.0001). “mus, sercpos. henophiliacs with HI. have nore impaired innune system than seropos. henqohiliacs withalt HL. 'Ihe observed prevalence rates appear to be lower than those so far re- ported arrong serqoos. honosexuals. The prognostic significance of these findings has to be elucidated. This study has been supported by the Danish Henrphiliac Society (Dannarks bloderforc—ming). 89 T2162 Routine Blood Cultures in AIDS Patients. TJ SPECH, MC MCHENRY, TF KEYS, C KARAFFA-MYLES, DL LONGWORTH, SJ REHM. Department of Infectious Disease, Cleveland Clinic Foundation, Cleveland, OH. Blood cultures (BCs) for bacteria are commonly drawn in the febrile . AIDS patient (pt) despite the relative infrequency of bacteremia Versus oppor- tunistic and non-bacterial infections. This observation prompted an analysis of the utility of BCs for 'routine' bacterial pathogens in AIDS patients. The charts of 65 of the 68 pts with AIDS followed at the Cleveland Clinic from 1981 through 1986 were available for review with attention to the number of positive and negative BCs, presence of central venous catheters, clinical diagnoses, and pt outcome. A total of 710 ECs for aerobic and anaerobic bac- teria were drawn on 60 patients. Only 13 episodes of bacteremia were detected, and 5 of these were due to staphylococcal infections of central venous cathe- ters. The remaining 8 episodes were primarily due to gram-negative bacilli from various sources: E. coli urosepsis, K. oxytoca pneumonitis, K. oxytoca biliary sepsis, E. coli of unknown source, and S. pneumoniae pneumonia. Two pts had polymicrobial bacteremia (due to paratracheal abscess and to sinusi- tis). Non-catheter related bacteremia was seen in pts with far‘advanced AIDS, always occuring several months after diagnosis (mean 358 days, range 169-898 days). Gram-negative bacteremia usually signified terminal disease with only one of 6 pts surviving beyond one month (mean 17 days, range 1-65 days). These data suggest that routine bacterial BCs in AIDS pts are of low yield except in the presence of central venous catheters or far-advanced disease. T2163 Prognostic factors for Pneumocystis carinii pneumonia requiring mechanical ventilation. WAFAA EL-SADR, and MICHAEL S. SIMBERKOFF, VAMC, New York, N.Y. Mechanical ventilation (W) has been reported to be associated with a poor prognosis in Pneumocystis catinii pneumonia (PCP). Records of 19 patients (pts) requiring MV in association with their first episode of PCP were analyzed. Group A (GA) consisted of 8 pts who survived; group B (GB) of 11 pts who died. The mean 25D of the duration of symptoms was 13:10 days and 23:19 days for GA and GB respectively (p=.03). Arterial oxygenation deteriorated and A-a gradient widened more precipitously in GA. The time from diagnostic bronchoscopy to initiation of MV was l.5:0.5 days and 617 days for GA and GB respectively (p=.001). MV was necessary for 614 (range l-6)days in GA and 19:16 (range 6-60) days in GB pts. Admission and peak serum LDH concentrations were similar in the 2 groups. However, LDH decreased by at least 40% from the peak level in all pts in CA by 5 days after intubation while it fell in only 4 of 11 GB pts. Con- comitant early infections were seen in 3 pts of GA (1 S. epid. sepsis, l salmonella sepsis and 1 mycobacterial isolate from the sputum) and in 7 pts in GB (3 S. aureus sepsis,4 S. aureus pneumonia and 2 mycobacterial sputum) (p<.05). We conclude that 42% of pts with PCP may recover from required MV. Factors associated with recovery include short duration of symptoms prior to admission, need for incubation shortly after bronchoscopy, early improvement in serum LDH levels and the absence of concomitant bacterial infections. TB164 Muco—cutaneous Manifestations in HIV Positive Subjects MARCO CUSINI, ROBERTO ZERBONI, GUIDO CARMINATI, ELVIO ALESSI - lst Clinic of Dermatology — AIDS Screening Centre - University of Milan - Via Pace 9, 20122 Milan — Italy He studied the muco—cutaneous lesions in 310 HIV positive patients attending our AIDS screening Centre. Two hundred seventy-seven were homosexuals, 30 were intravenous drug abusers, 3 were heterosexual males. Fifty—four were asymptomatic carriers (Vslter Reed 1), 137 had persistent generalized lymphadenopathy (HR 2), 98 had ARC (UR 3,4,5) and 11 had full blown AIDS (WR 5K,6). Among this group 93 patients (301) had mucocutaneous lesions. We considered 3 main categories: infective, tumoral and other. Morphological, histological, immunohistochemicsl and electronmicroscopic studies were performed. Viral infections were caused by herpes virus in 30 patients (9,671), human papilloma virus in 20 (6,h51) and by both viruses in 10 patients with Oral Hairy Leukoplakia (3,221). Only 3 patients were affected by bacterial folliculitis. Oral thrush was present in 12 subjects (3,821) while other dermatomycosia were found in 7 subjects (2,151). Five patients (1,611) had muse-cutaneous Kaposi's Sarcoma. An important role was played by Seborroehic Dermatitis that was present in 26 patients (9,381) often with widespread lesions resistant to therapy. We also observed subjects with Yellow Nail Syndrome, Immune Complex Vasculitis, severe Psoriasis. Some of the skin disease: we observed had a strong relation to the clinical stage of immune-depression; five out of 12 patients with oral thrush also had Candida Esophagitys and 5 out of 10 patients with Oral Hairy Leukoplakia developed full blown AIDS within the year. TUESDAY, JUNE 2 TR165 Pneumocystis Carinii Pneumonia (PCP) : value of Pulmonary Function Tests (PFT) follow up. FRANCOISE CAMUS, S. MATHERON, P.M. GIRARD, E. AOUSSI, J.F. FOULT, A.G. SAIMOT et al. HOpital Claude Bernard. PARIS. FRANCE. Among 52 AIDS patients (pts) admitted from 7/84 to 9/86 with BAL proved lst episode of PCP, 19 were followed up by serial PFT over a mean period of 10.2 1' 4.2 months. Tests were : transfert lung capacity for carbon monoxide (TDCO) (N ) 80% of the predicted value by steady state method, corrected for anemia) and alveolar arterial gradient for partial pressure of oxygen (A - a)0 (N \< 20 torrs) . PCP relapse occured in 6/19 patients. None of them had specific maintenance therapy. At the time of let PCP, PFT revealed significantly low 'I'LCO (49.8 i 12.5) and major hypoxemia (A - a)0 = 41.4 - 13.7). In all 19 cases, PF'I‘ values 1, 2 and(5 — 1)months after st PCP episod were subnomal(TDCO = 85.6 1 21 (A - a)0 = 16.9 t 9.64); with no significant difference between patients with/ without relapse. + Relapse was suggested within 8.8 — 1.6 months after ist PCP by sudden de— crease in TLCO (53.75 - 5.85) and severe hypoxemia (40.2 I 11.7) in His $liX'.PtS- Three of them had no radiological changes at that time. TIJCO and (A - a)0 one month later were 68.5 t 20.9 ; 22.6 i 9.5). 2 PPT follow up in these pts showed : 1) normalisation of both TLCO and (A - a)02 one, two and five months after ist PCP, and no predictive value for PCP relapse ; 2) sudden deterioration preceeding x Ray changes in 3/6 cases, at the time of relapse ; 3) More severe changes in mm and (A - a)02 one month after relapse/one month after lst PCP. TR166 Chemoprophylaxis Prevents Recurrence of Pneumocystis carinii Pneumonia (PCP) in Retrovirus Induced I-unodeficiency (AIDS) D CRAIG WRIGH’N, J1. RHOADS, J MCNEIL, DS BURKE, RR REDFIELD. WRAMC', “AIR, Hashington DC Fifteen patients with biopsy proven PCP and HIV induced immunodeficiency (AIDS) were evaluated. After recovery from the initial episode of PCP, two patients received no chemoprophylaxis while 13 patients received chenoprophylaxis with either one tablet weekly of pyrimethamine- sulfsdoxine (FAN), or one tablet trimethoprim—sulfamethcxazole 80mg/400mg twice daily (TMP-SXT). Recurrence of biopsy proven PCP was noted in both patients who did not recieve chemoprophylaxis, A and 8 months after original PCP episode. These two patients were subsequently placed on chemoprophylaxis after their second episode of PCP. No patient (0/15) recieving prophylaxis redeveloped PCP. Six of fifteen died during follow up period (mean time to death 10.3 months, range 2-31 months). Three of these six had post mortem examination; none had histological evidence of PCP. Nine of fifteen still survive (mean follow up 13.7 months, range 6-22 mnths). Chemoprophylaxis was highly effective in preventing recurrence of PCP (p (0.001). Although both regimens were effective in preventing recurrent PCP, a trend toward increased mortality was suggested in the TMP-SXT group. In the FAN regimen group there were 1 death/th man months of follow up as compared to the TMP-Sx'l‘ group with 5 deaths/91 man months of follow up ( p-0.07). A placebo-controlled trial is currently in progress to determine the efficacy of PAN chmoprophylaxis prior to the initial episode of PCP in Walter Reed stage 5 and 6 patients. Bsophagal Candldiesis in sk Patients for . T2167 murmured J.M£%.,J.M,J‘.wncgfectim niece sol Unit, (Instructor-clog and Hematolcg .Hospitsl do Badalana "tbmsna his 1 91501".Bedalona.3arcclcna.cstalonia.3paln lsophapal candidiaais m be symptomatic and not assoktcd. with aral thru- sh.’1‘o evaluate its pmvalencc in we: ms for All! we endoscopsd 50 ps- tients(45 intravenous dung addicts and 5 hmsenmlsfilrcugh 1986.Nons had o— ral thrush or esophageal symptoms.Forty had generalised lymphadenopsthp.flonc fulfilled AIDS criteria at admissioncdll but 2 had antibodies to HIV defected 1w ILISA methodJn 9 of them esophsgcscopy showed plumes of white cmdate,soa— taxed. in m.Qytologlo animation of esophageal demonstrated codi- diasia in all thouLBdcpsv was positive only in 2 cases probably because of saw pling error in dealing with scattered fool of fungal involvement.1n those 2 or sea biopsy showed only modes-stew“ invasivcwsophaatiam out of nine was mgativc for HIV antibodicdal’etients with esophageal oandldlssls have ben ad- mitted because of idiopathic thrcmhoqytopendc pnrpura in 2,:ight-sddsd endocan- «111:1. 1n 2(:l.n 1 associated also to a pulmonary tobarculosis),constitutlonal cu.- seaso(group IV}suhgrcup A)1n 2 and coocoal scpsds,pnoumonis and left son a» 11mm. in the 5mm median '1' ratio in this M was 0.55(rsngs 0.13 to manna follow-up during this year has not chm the evolution to mom. 2 cases“ of them with positive 121.0pr demonstrated,w esophagoscopwuponts- naoua resolution without treatment at 10 days interval.Tha other patients reco- lwd. c 10 days course at oral kstoccnssoldmtunatic candida infection of fin esophagus is not an unocmncn disease in patients at risk for £15,“: new dio- appcar spontaneously, is not associated with unfavorahln outcome and should not he considered a criterion for AIDS unless shown clearly insaslvs 1V biopsy. Serum Adenosine Deaminase Level; A Simple Screening test for Disseminated Mycobacterial Disease in Patients Seropoaitive for Human Immunodeficiency Virus DEBRA FERTEL, K. MILLER, R. UTTAMCHANDANI, A. PITCMENIK, G. MUM. University of Miami/Jackson Memorial and VA Medical Center, Miami, Florida. Adenosine Deaminase (ADA), an enzyme of purine metabolism, is produced by activated T—lymphocytes and plays an important role in T—cell maturation. Surprisingly, this enzyme has been reported to be normal in the T—lymphocytes and high in the null lymphocytes of patients with the Acquired Immune Deficiency Syndrome (AIDS). We measured the serum levels of ADA in 32 hospitalized patients with positive serology for Human Immunodeficiency Virus (HIV) and 33 age matched control subjects (hospital personnel). ADA was analyzed by the standard Giusti and Galanti colorimetric method. Among the seropositive patients, l2 had Pneumocystis carinii pneumonia, 13 had myccbacterial disease (9 with histologic or culture proven disseminated disease and A with pulmonary tuberculosis), 2 had Kaposi's sarcoma and 5 met the criteria for AIDS related complex. The mean serum ADA was 7h.78 IU/L (range 64.1-103.l) among the patients with disseminated mycobacterial disease; 72.7 IU/L (range 27.9-102.7) among the patients with pulmonary tuberculosis; 38.9 IU/L (range 17.1-56.1) among the 19 HIV seroposltive patients without mycobacterial disease and 21.8 IU/L (range 11.9—42.6) among the healthy control subjects. The ADA level among the HIV seropositive patients with mycobacterial disease was significantly greater than that of the HIV seropositive patients without mycobacterial disease (p<.0001) and also greater than that of the healthy subjects (p<.0001). Measurement of serum ADA is a simple test which may prove clinically useful in screening for the presence of disseminated mycobacterial disease among patients seropositive for HIV. TP.168 TR169 Splenomegaly and Extrapulmonary Disseminated Pneumocystis carinii Infections in Patients with AIDS A.M. MACHER‘, C. STEIGMAN**, L. PASTORE**, D. KAHN***, J. GARFINKLE***, M.L. DEVINATEA*, et. al., ”Registry of AIDS Pathology, AFIP, Washington, D.C., MFairfax Hospital, Falls church, VA, **"Sherman Oaks Community Hospital, Sherman Oaks, CA We studied the clinical course, surgical and autopsy pathology of 2 patients with AIDS who developed pulmonary and extrapulmonary disseminated infections caused by Pneumocystis carini_i. Patient 1: A 32 year old white male homosexual with left upper quadrant pain had splenomegaly and inguinal lymphadenopathy and was HIV sero-positive. He he— came febrile and an abdominal CT scan revealed focal defects in the spleen. At splenectomy, the spleen weighed 2000 grams and contained grey-white nodules; microscopic examination revealed foci of eosinophilic foamy necrosis containing cysts of _P_. carinii. He died 1 month later and autopsy revealed necrotic foci containing 3. carinii in lymph nodes, liver, kidneys, ureter, jejunum, omentum, mesentery, appendices epiploicae, pancreas, adrenals, heart, thyroid, bone mar- row, choroid and lung. Patient 2: A 48 year old white male homosexual with fever, cough and progres— sive dyspnea was hronchoscoped and g. carinii pneumonia was diagnosed. He was HIV sero-positive and died 6 days later. At autopsy there was a 250 gram spleen containing white nodules and microscopic examination revealed 3. carinii in spleen, lymph nodes and lung. Although infection with 1:. carinii is typically confined to alveoli of the lung, in the immunodeficient host it may disseminate. The patients in this re- port developed splenomegaly as part of their disseminated extrapulmonary 3. cari ii infections. Clinicians and pathologists should be aware that E. carinii may infect organs other than the lung. T2110 Congestive Card'lomyopathy in Association with Acquired Immune Deficiency Syndrome in Children V. JOSHI, CHARLES GADOL, E. CONNOR, J. MENDELSON, J. MARIN, J. OLESKE Children's Hosplta of New Jersey, UMD New Jersey Medical School, Newark, NJ At autopsy in 5 children with AIDS, dilated cardiomyopathy characterized by a) enlargement of heart with biventricular dilatation, b) rare foci of myocardial necrosis with minimal to m1ld inflamatory infiltrate, c) hyper- trophy, d) interstitial edema and myxo'ld change, 3) mild focal interstitial fibrosis, f) vacuolation due to fatty change, 9) focal pericardial inflamntory infiltrate and h) endocardial fibrosis was seen. Two of the patients had de- veloped congestive heart failure. Candid'lasis, Aspergillosis, CMV or M. avium intracellulare infection was present in one pat1ent each; mild focal calcifi cation of small branches of coronaries without luminal narrowing was present in one patient and noneof the patients received any drugs conmonly associated with hypersensitivity reactions. These factors are unlikely to be related to pathOgenesis. Anemia, nutritional deficiency, infection and undetermined type and inmunolog1c factors may play a role in the pathogenesis of cardiomyopathy in these children. TUESDAY, JUNE 2 T8171 ex KAROLVNN SIEGEL, F. MESAGNO, J.Y. CHEN, G. CHRIST, Memorial Sloan—Kettering Cancer Center, New York, NY, USA. A longitudinal study of patterns of sexual behavior among asymptomatic, homosexual males (N=161) in New York City was conducted. Participants were interviewed at two time points six months apart. Based on their reports of sexual behaviors during a recent "typical" month, respondents were classified at each time point as engaging in safe (or low risk) sex versus risky sex (e.g.. unprotected anal intercourse or oral-anal contact). Discriminant analysis was employed to distinguish the 48 males classified as safe at both T1 and T2 from the 58 males classified as risky in both periods. Statistically significant discrimination (Wilks' lambda = .675) was parsimo- niously achieved through the use of seven predictor variables: drug use during or in anticipation of sexual activity; living with lover; number of years engaged in regular sexual intercourse with males; perceived emotional support; fewer friends or acquaintances with AIDS; self-esteem; and alcohol use. Of the predictors, drug use within sexual contexts is particularly noteworthy, since it provided the greatest relative contribution to the discriminant function and appears to be an important candidate for educational interven- tion. Among the variables which did not significantly contribute to this discrim- inant function were: gay network affiliation, denial of AIDS threat and com- fort negotiating sexual limits. The significance of these findings for public health efforts will be discussed. Factors Distinguishing Homosexual Males Practicing Safe and Risky TP172 A National Survey of Public Concern Regarding AIDS SHIRLEY DAMROSCH and B. BAUSELL, K. SOEKEN AND P. land School of Nursing, Baltimore, MD. A survey on acquired hmmunodeficiency syndrome (AIDS) was conducted using a national random sample of 1,256 adults; the poll utilized random digit dialing and achieved 70% participation. Those with higher levels of education (at least a high school diploma vs. those without diploma) were somewhat more opthmistic that AIDS would be under control five years from now (48% vs. 40%) and less pesshmistic that AIDS would become a major epidemic (12% vs. 21%). Although only 10% of the sample perceived themselves at any risk of catching AIDS, 41% reported taking special precautions to avoid catching the disease. Perceptions of risk were highest among college graduates (16%), those aged 30—39 (16%), and those living in the East (16%). Blacks (61%) and Hispanics (58%) were more likely to report special precautions than were whites (37%). of the total sample, 79% agreed either strongly (47%) or somewhat (32%) that the governnent should spend whatever it takes to find a cure or vaccine. Seventy percent of the total agreed either strongly (50%) or somewhat (20%) that the government should impose restrictions on gay bars and bath houses during the epidemic; there were educational differences on this issue, with 77% endorsement among those with high school or less, dropping to 62% for those with at least some college. Highest endorsement (97%, 88% strongly and 9% somewhat agreeing) was given to the proposal that individuals should take extra care in sexual relations and personal preventive habits. PARKS University of Mary— TP173 AIDS and the College Campus: A model Prevention Program ' CATHY KODAMA,MPH, MARY O'DONNELL. MPH, Cowell Hospital, University of California, Berkeley, CA. Approximately 12 million students are enrolled in colleges and universities in the United States, representing about 5% of the population. In California alone, between 9,000 to 45,000 students currently enrolled in institutions of higher education can be expected to develop AIDS or ARC. Upon entering college, the sexual networks of young people suddenly expand and experimentation with a variety of sexual practices, including bi—sexuality is common. A significant number of students also drink alcohol excessively and engage in recreational drug use. This leads to impaired judgment regard- ing sexual behavior and responsibility. For the most part, the threat of AIDS and death does not seem real to college students who believe themselves invin- cible. The purpose of the poster session is to present a model for campus—based AIDS prevention. The model was developed and tested at the University of Cali— fornia, Berkeley in 1986—87. The State of California Department of Health Ser- vices contracted’with Berkeley to design and disseminate this model. It is currently being replicated at other institutions of higher education. The poster session will highlight theoretical principals of AIDS education for this target group, with an emphasis on community organization and peer education. A 60 page training manual for campus AIDS educators wil be showcased along with institutional guidelines for policy development. 91 TR174 Determinants and Effects of HIV Antibody Test Disclosure. JANE MCCUSKER*, J.G. ZAPKA*, A.M. STODDARD*, K.H. MAYER**, J.S. AVRUNIN*, S.P. SALTZMAN***, et 81., *University of Massachusetts/Amherst, Amherst, MA, U.S.A., **Memorial Hospital and Brown University, Providence, RI, U.S.A., ***Fenway Community Health Center, Boston, MA, U.S.A. The role of HIV antibody screeningof high-risk groups is an unresolved public health issue. This study identifies the differences between individuals who choose to know vs. not to know their results and explores the impact of knowledge of HIV antibody test results on subsequent behavior. In a longitudinal study of initially asymptomatic homosexual/bisexual men (N=290) at a Boston community health center, 23% of the participants chose not to know their initial test result during the following six months. Antibody positive and negative men were equally likely to be informed. Multivariate analysis determined that the following variables were associated with the decision not to be informed: greater perceived severity of AIDS, lower reported effort to change sexual behavior, greater exposure to informational activities, and age 25-29. Significant differences were found by antibody status and test disclosure in emotional reactions (anger and depression) during the six months following test disclosure. Both emotional reactions and correlates of the decision to be informed should be considered in interpretation of subsequent behavior. TR175 Campaign to Promote Safe Sexual Practices in the Montreal Homosexual Population - Quebec ALIX mammal“, J. CARSLEY,(1,2), s, IoANNou,(1), (1): Community Health Department, Montreal General Hospital, (2): Departments of Family Medicine, Epidemiology and Biostatistics, McGill University, Montreal, Quebec, Canada. with an AIDS community group (C—SAM) we developed a program to promote safe sexual practices among Montreal's homosexual population. Focus groups were used to review educational materials and extensive coverage by various gay media was provided. During a one week educational campaign, ten thousand health education pamphlets on "Safe Sex" and the same number of condoms were distributed in 27 gay bars and clubs, and S saunas by 30 trained health promotion volunteers. A month later, a self-administered questionnaire was distributed in representative establishments. The response rate was: 77.9%. of the respondents 79.31 had heard about the campaign and 50.9% had read campaign pamphlet. Of those who read the pamphlet, 57.11 thought it had influenced their sexual behaviour. 452 of those who reported the campaign had an influence on their behaviour reported condom use compared to 19.61 of those who denied an influence of the campaign (X2=49.03, ps10.001). 18.91 of those who denied influence could not identify passive anal intercourse without a condom as high risk while only 10.8% of those reporting influence could not. This project shows the feasability of a community preventive intervention in a population at high risk for AIDS. six 839 the "AIDS Community Outreach for Intravenous Drug Users" Harvey H. Feldman, Ph.D. 5 Patrick Diernacki, Ph.D. YES Project, 1779 TR176 [Height St., San Francisco, CA 94117. In May 1986, a community health education/outreach program was created in San Francisco to stop the spread of AIDS among intravenous drug users (IVDUs). Currently, the program employs eight workers who provide AIDS education, counseling and referral to drug users in those areas of the city that contain the highest concentrations of IVDUs. This paper describes and analyzes the major stages undergone since the program's inception and addresses problems encountered. The annlvsis will help other communities to develop similar outreach efforts. The program developed in the following stages: 1) Formation of the overall strategy guiding the program effort toward the major goal of stopping the spread of AIDS among IVDUs; 2) Ethnographic studios of target areas to map out & analyze the needle-using scenes and drug-using practices; 3) Recruit- ment & training of an outreach stuff component; A) Successful entree into the target community; 5) Development & distribution of health promotion materials, condoms and small bottles of bleach; 6) Use of indigenous field assistants, who are natural leaders, to help promote safe health practices; 7) Utilization and management of the media to promote the project'l goals; 8) Evaluation and reassessment of project plan and ensuring compliance with health messages, & 9) Entry into new IVDU scenes, when and how to move beyond the original target groups. An administrative project evaluation indicates that, contrary to popular wisdom, IVDUs will change their behavior, especially in relation to sani- tizing their shooting paraphernalia. TUESDAY, JUNE 2 TP117 Utilization of HIV Alternate Testing Sites in Upstate New York JOHN C. GRABAU, M.P.H., PH.D.,* BENJAMIN I. TRUMAN, M.D., M.P.H.,** DALE L. MORSE, M.D., M.S.,** AIDS Institute* and Bureau of Communicable Disease Control,** NYS Department of Health. Albany, NY In June and July, 1985, the New York State Department of Health established HIV Counseling and Testing sites throughout New York State exclusive of New York City. Between June, 1985, and October, 1986, 7,608 persons received pretest counseling at the sites. Just over 69% of those being counseled elected to have the HIV antibody test (N=5,283). of the 5,161 persons receiving posttest counseling during the 17 month period, 13% were positive via ELISA and Western Blot for HIV. Individuals submitting blood for HIV testing were asked to voluntarily complete a questionnaire assessing demographic and HIV associated variables. of the 2,788 (53%) completing the questionnaire 70% were males. The ages ranged from less than 15 to greater than 55 with 89% falling in the 15 to 44 year age group. The preponderance of those using the alternate site considered themselves to be white (84%). 0f the 1,833 who considered themselves to be a member of a risk group: 44% were homosexual; 21% were bisexual, and 24% reported IV drug use. The two most common reasons for wanting to be tested were risk group membership and sexual contact with a risk group member. Nearly 80% considered themselves physically well at the time of testing. TR118 HIV Antibodg Testing Qualitative Outcomes MICHAEL GROSS, Ph.D.’, MARSHALL FORSTEIN, mom", "Gag and Lesbian Counseling Service, Boston, MA, ‘"The Cambridge Hospital, Cambridge, MA Despite near universal opposition by the gag communitg in April 1995 to AIDS antibodg testing the Gag and Lesbian Counseling SerVice (GLCS) took a pro- active stance, working with the state Department of Public Health to design and implement a network of alternative testing sites. He describe the rationale for that decision and outcomes of two gears of participation. Bg participating in program design GLCS fostered principles fundamental to the Massachusetts program: (1) total anongmitg, (2) an emphasis on education, especiallg about risk reduction, rather than on testing, and (3) access to a network of AIDS-aware medical and mental health providers sensitive to issues specific to high risk populations. A keg contractor with the Department in staffing/supervising several sites, GLCS also created and maintains a statewide proVider referral list. within its service region, GLCS provides both acute and long-term mental health services to test site clients withut regard for their abilitg to pag. The changing composition and issues of test site clients forecast trends in service needs. GLCS flexiblg responded to program needs bg: (1) adding a voluntarg (anongmous) second follow—up Visit several weeks after individuals testing poSitive learn their status, for further help with referrals; (2) creating a “Safer Sex Psgchoeductional Group“ for ATS clients and others in the communitg; (3) sponsoring a support/educational group for pregnant women at risk through needle sharing or a sexual partner who has shared needles. Other needs identified concern links between drug/alcohol use and unsafe sex, specific issues for bisexual men in long—term relationhips with women, and short— and long-term adverse sequelae of learning one’s antibodg status. and Communitg Mental Health: of a Collaborative Model TB179 The Alternative Test Site (ATS) in Rhode Island JACK BRONDUM, B. DEBUONO, L. DONDERO, J. HODGE, A. JOHNSON, Rhode Island Department of Health (RIDH), Providence, Rhode Island, USA. An ATS was established at the RIDH in June, 1985, to provide anonymous test- ing and counseling for Human Immunodeficiency Virus (HIV) infection to persons who might otherwise have gone to blood donation centers to be tested. As of January 28, 1987, 862 persons had attended. Median age was 31 years; 644 (75%) were male. 835 (97%) persons had their blood tested, 794 (95%) of whom belonged to groups at high risk for HIV infection. 406 (63%) males cited homosexual activity as a risk factor, and 116 (53%) women cited sexual contact with a high- risk individual. HIV infection was confirmed in 74 (9%) persons; 71 (96%) belonged to high- risk groups. 65 (88%) were male, of whom 55 (85%) were homo/bisexual and seven (11%) were intravenous drug abusers (IVDA). Five (56%) women were IVDA, three (33%) were sexual partners of IVDA. Among non-infected persons, I39 (54%) seen at the ATS from July through December, 1985, would have donated blood to determine their HIV antibody status if the ATS had not been available, while only 106 (40%) seen from July through December, 1986, would have done so (X test for trend=lO.2, p=0.0014). 23 (31%) infected persons would have donated blood. The ATS in RI serves a population at high risk for HIV infection and plays an important role in monitoring HIV seroprevalence in this population. It has also served to divert infected potential donors from blood donation centers. 92 TE130 Attitudes towards HIV antibody testing sumo corral Proctlllmors W" .J B BRUNEI“, E BOUVET" .A-J VALLERON *. * Unllo do Recherche Blmnalhémathuss at Blostotlstlmes (URBB) INSERM at Unlvorsllo Paris 7, '* DIroclIon Male 6 la Sanlb .Bureou dos molcdles lronsmlsslbles. Paris. In order to evaluate the use of HIV ontlbody lestlno by normal practitioners ( 6P5), a spscmc questionnaire was sol up on the Frenm Communicable Diseases Network In November I986. This network . ssiobllshod In I984 for the surveillance of certain commumcoble diseases. links 250 sentinel general proclllloners ( SGPs). by electronlc mall to a central computer These 6P5 were asked to report all prescriptions mom for HIV antlbody Iestlnq and to provide, for each case. the following Informallon : person requesting test ( Le. pollen! or 6?). reason for test. Westerlshos or pallent, result of test and dlapnostlc method 5) load. After we month of the study. preliminary results Indicate that 14% (36/250) secs had prescrlbed at least moo a test for a total of 65 sublects The overall perwnlope of patients spontaneously asklng for lhe test was muddy 503. However lhls percentage was MW In mole homomuols (69%) than in IV drug users (33$). demonstrating the strlklnu dlfferonca In the altitude In these two groups. Thirteen subjects were and HIV posItIve. 7 of mm Demo IV mo users. Routine collection of Informatlon wIll provide lurlher data on GPs' altltudes towards HIV tsstlno, clIaractorlslIcs of toslod sublecls and help In adapting MIMI prowoms devoted to health care professionals. TR181 JUNIOR AND SENIOR HIGH SCHOOL STUDENT'S KNOWLEDGE ABOUT AIDS: THEY WANT TO LEARN MORE AND WANT TO LEARN IT AT SCHOOL STEVEN D. HELGERSON, and the AIDS Education Study Groups, Yale University Department of Epidemiology and the Connecticut State Department of Health Services, including William Sabella. We assessed knowledge about AIDS from 657 junior and senior high school students randomly selected from required English classes in two Connecticut school districts. Although many students had some factual knowledge about the virus that causes AIDS, many students were misinformed about methods of viral transmission, high risk groups for developing AIDS, and methods to avoid acquisition of the virus. Importantly, 58% did not recognize the existence of an asymptomatic carrier state; and 63% and 59% respectively did not recognize the potential for vertical transmission from fathers or mothers infected by I.V. drug use. Responses from students of different grades, ages, sexes, races and school districts, differed rarely and without apparent pattern. Students reported they had learned about AIDS mostly from television or radio (57%) or magazines or newspapers (16%); while few had learned from persons with whom they had frequent contact, such as parents (6%) or teachers (4%). Seventy- four percent of students said they wanted to learn more about AIDS, and 49% said they wanted to learn it in school. We conclude that students' knowledge about AIDS is not adequate, students wish to learn more, and information about AIDS should be presented in public schools. TP132 'De AIDS/STD EDUCATION PLAN - An Innovative, Effective and Cost Ef- ' ficient Program for Schools to Teach AIDS Education and Achieve the USPHS 1990 STD Education Objective STEPHEN R. SROKA*, L.CALABRESE**, T.JONES***. *Cleveland State University and Cleveland Public Schools, Cleveland, OH, **Cleveland Clinic, Cleveland, OH, ***Wisconsin Dept. of Hlth, Madison, Wisc. The AIDS/STD EDUCATION PLAN is a response to the Surgeon General's Report on AIDS and to the USPHS 1990 STD Education Objective which encourage educators to teach students AIDS and STD education. The AIDS/STD EDUCATION PLAN is a teacher training program based on the Ehre— tor's Guide to ABS and SlD's, a behavioral approach to teaching AIDS and STD educa— tion in a communicable disease conceptual framework, which is easily implemented in all schools. 0W5 ZED ahmauxs Mn uxmh we! WD,GD glflens in3 Ehxznxns (N: 520) ENaluation Dun: Objective: % enrauxs states use the AflflhfiflD EIIKNHTIN FlAN. ~ H II, . offered effective nettnds and mterials . node SID's easier to teach (W) to teach soikaus how to: . posited significant ahrathmrfl — nannyuze symmxns (HIE) gIbB in snxkntsfi —fhfl,imechnfl£ (an) —knmdekp (§fl) —refir an pntmfls fix mflizfl axe(8%) —aufituk£ (m1) — follow tnznmrrm instnxnjrns (93%) - bdrndrnal inuauicns (77%) —awflfi $D's (9n) .wfll ma delifide ' gfl The AIDS/STD EDUCATION PLAN is cost efficient. Ohio achieved the 1990 STD Education Objective for less than 7¢ per students. The AIDS/STD EDUCATION PLAN offers a prototype for schools to teach AIDS edu- cation and achieve the 1990 STD Education Objective at the city, state or national level. TUESDAY, JUNE 2 TR183 Lessons of History: An Examination of the US Army Pre-Antibiotic Venereal Disease Control Program and its Application to HIV. CHARLES F. CLARK, M.D., AUSTIN C. KUHN, Msw, SHAPE Hospital, Casteau, Belgium, RAY MOEHRING, Boulder, CO, EDMUND C. TRAMONT. M.D., Walter Reed Army Institute of Research, Washington DC. The venereal disease control program instituted by the United States Army in 1911 contained the following elements: Monthly lectures by medical officers about human reproductive physiology, the transnission and course of venereal diseases and an explanation of why sexual intercourse was not necessary to a healthy body, calmanding officers expounding on the duty to renain healthy, chemical prophylaxis within two hours after fornicating, chaperoned social activities on Post, and pay withheld while in treatment. The Army applied this program to every cormnand on every Post in every part of the world where there were soldiers. The full program was applied regardless of variations in local circumstances and regardless of the ethnic, educational or cultural background of the troops. This Army wide program does appear to have caused a slow, progressive decrease in the venereal disease rate in the Army as a whole, but the reduction of the rate varied enormously with racial, geographic, and cultural factors. History has for us an important lesson. A single massive aggressive intense repetitive educational campaign to control the spread of HIV in the United States will not be effective in stopping the HIV epidemic, and will slow it only modestly. There must be a campaign of a thousand parts, each directed towards a specific racial, economic, intellectual, social, political group and addressing specifically the issues critical to that group's sexual behavior. We need a rapid, rigorous rethinking of our educational programs and other efforts. T2184 Sharing of Paraphernalia in Intravenous Drug Users (IVDU): Know- ledge of AIDS is Incomplete and Doesn't Affect Behavior. NEIL M_. FLYNN‘, S. JAIN', S. HARPER‘, V. BAILEY", R. ANDERSON", G. ACUNA", et al. ’Univ. Calif. Davis, I”Sacramento AIDS-IVDA Taskforce, Sacramento, CA. Transmission (T) of HIV among IVDU in the 0.5. is occurring rapidly. Ef- forts at reducing this spread have been ineffectual. The potential for heterosexual and vertical T by‘this population is enormous. To determine causes of rapid spread we examined knowledge and behavior of 200 IVDU at- tending Sacramento(s) drug abuse clinics. Most addicts believed that: HIV was present in IVDU in S (905); they would eventually acquire HIV if they continued sharing paraphernalia (P) (931); HIV can be transmitted hetero- sexually (91$), vertically (100$); condoms can prevent sexual T (614%). 951 wanted to avoid acquiring HIV. With respect to behavior last time they shot up, however: 751 used own P, but 775 shared it; 871 cleaned P between users, but only with water, rarely disinfectant; majority (701) had potential disin— fectant solution readily available (bleach 351, rubbing alcohol 565, peroxide 31!, wine 235). Addicts expressed: surprise at rate of HIV spread; ignorance of potential disinfecting agents, methods for cleaning P; reluctance to carry P because of criminal possession laws; strong desire to continue sharing F. We conclude: some knowledge of HIV epidemiology exists among IVDU; IVDU are not aware of imminent risk of infection; knowledge of disinfection is dismal, rarely acted upon; sharing is likely to continue because of social aspects, criminal possession statutes. Immediate intervention, emphasizing AIDS risk, practical P disinfection methods and condom use is warranted. Failure to effectively intervene will result in rapid heterosexual and vertical T of HIV from this population. TP185 Follow-up to Ensure Counseling of HIV—Ab Positive Volunteers to ‘ HIV Test Sites (ms) NANCY E. SPENCER. B. DILLON, G. HARE, J. LESLIE, Colorado Department of Public Health, Denver CO . U.S.A. Confidential post-test counseling of volunteers for HIV-Ab testing gives positive persons an opportunity to learn their antibody status and receive personalized instruction on methods to prevent HIV transmission. Subsequent practice of safer sex and no needle share behaviors should reduce community transmission of HIV. Confidential (non—anonymous) testing and reporting allows public health follow—up of positives who fail to return for test results and counseling. Public Health can ensure (with provider consent) knowledge of test results and appropriate counseling for positive individuals. During 1986, 109 HIV-Ab positive individuals for whom there was no record of post-test counseling were followed by the Colorado Department of Health. The results were; 20 (19%) were brought to counseling. 33 (sex) had been previously counseled. 47 (43") were not located, and 9 (8x) refused test results and counseling. Follow-up revealed that 82 (75!) positives provided accurate locating information at the time of test, but the proportion located and counseled decreased as the time interval between test and follow-up increased. Assuming that without counseling, each positive would transmit to 1 other individual, and that 409. of HIV-infected individuals experience some serious HIV-related morbidity, 20 new HIV infections, 8 of which may have developed AIDS or ABC, may have been prevented through this activity. Confidential testing and reporting, coupled with rapid and active follow—up of uninformed seropositives by public health can affect counseling and help reduce community transmission of HIV. 93 TR186 AIDS Knowledge in Urban vs Rural Washington State High School Students. SHAW“ HOPKINS, A. MINER, L. MILLER. Seattle—King County Department of Public Health: Seattle, Washington, U.5.A. ll‘B surveyed Nth—grade students to assess AIDS knwledga as a basis for curricula development and to carvers urban and rural students. Of 502 students surveyed, 214 were from urban King County (pop. 1,350,E03: 3CD AIDS cases): 238 were from rural Clallsm County (pop. 52,030; 1 AIDS case). Practically all students (955) identified blood and semen as likely to spread HIV, but 39$ thought saliva a likely source. Students recognized male transsexuals and Ill drug users as risk groups, yet 48! thought fanale hmsexuals at high risk. One in 5 thought living in the same household as someone with AIDS was risky, 32! thought AIDS could be acquired mile donating blood; 27! thought mosquito bites a transmission source. Responses to indivimal knowledge questions varied little between urban and rural students. When the 2 groups were camper-ad for percent correct responses on 34 knowledge questions, there was no difference (72! vs 70! correct). Significantly mars urban than rural students wanted to know more about AIDS (70% vs 55!). Ms concluded: 1) Both urban and rural students have basic knowledge of AIDS 2) The same misconceptions were prevalent in both groups 3) Rural students may not feel the need for AIDS situation as acutely as urban students A) One curricula is suitable for both urban and rural Washington State students. "3187 Prevalence of Antibodies to HIV in Prostitutes and Dominican and Haitian Cane Cutters in the Dominican Republic. gJLIIN mono: L.DE CASTROHJ. ACRA***,S.CASASNOVA"*,C. CUNIHERAW and J .A.IEVY****. *laboratorio Nacional de Salud Publico,**Univ. Autonom de Santa Domingo,*”Univ. Nae. Pedro Henriquaz Urefia, *WCancer Research Inst., Univ. of California. San Francisco. California In recent nonths,10 femlo prostitutes have returned to the Dominican Republic from neighboring islands and their seropoeitivity to HIV confirmed at the Natiorml laboratory of the Public Health Ministry. To examine the extent of AIDS seropositvity in resident Dominican prostitutes and heterosexml m1 agricultural workers known to associate with prosti- tutes, two studies were undertaken using commercial ELISA kits and immunflor- escenco or Western blot to reconfirm. One hundred thirty nine prostitutes in Santo Domingo were questioned and bled. Two individual were seropositivs. No correlation was found with kind and extent of sexual activity, VD, or relations with non-Dominicans. Two hundred cane cutters of Dominican or Haitian origin residing within a 20 km radius were studied. Although they work in the some fields. these men live in separate areas, depending on rationality. The same fennlo prostitutes, though, do imtermingle with both groups. The health of the Haitians was consid- erably better than the Dominicans, using AIDS symptoms as criteria. More Domin- icans reported venereal diseases. Nevertheless, 2 Haitians and no Dominicans were seropoaitive. No significant factor could be found to explain the scro— poaitivity in these two. It is therefore assumed that they were infected through heterosexual sex in the Dominican Republic or lhiti. These results indicate that heterosexual transmission from local prostitutes does not represent a serious threat now, but the intermtional trade could pro- vide a way for HIV to enter the rural and, urban heterosexual population. - Perceived Changes in Sexual Practices Among Homosexual Men DON JOHNSON and H. M. MCGRATH, The University of Texas Health §cience Center at San Antonio, TX. The study surveyed 343 gay men in three Texas cities regarding their sexual practices during the last 30 days of this year (current sexual practices) compared with their sexual practices the same 30 day period one year ago (past sexual practices). The survey consisted of 16 items regarding current sexual practices and the same 16 items regarding past sexual practices. Behaviors were rated from 0 (low risk) to 5 (high risk). The mean scores of each current sexual practice were compared to each past practice using the Hilcoxon Matched-Pairs Signed-Ranks Test. Results indicate that the present sexual practices compared to past sexual practices are significantly less risky for contracting AIDS. Significant differences were found in the following high risk behaviors: anal receptive sex (Z = -4.1969 p = <0.0000); anal insertive (Z = -4.9605 p = <0.0000); oral receptive (Z = -5.0503 p = <0.0000); oral insertive (Z = -5.2322 p = <0.0000); location of meeting partners (Z = -5.9669 p = (0.0000); rimming (Z = -4.7041 p = <0.0000); swallowing of semen (Z = -7.8294 p = <0.0000); use of intravenous drugs (Z = -14.3138 p = <0.0000) number of sexual partners (Z = -6.9269 p = (0.0000); anonymous sexual partners (Z = -6.0697 p = <0.0000); sharing of anal sex toys (Z = -2.8571 p = (0.0043). Although there are significant differences between current and past sexual practices, the study shows that 25.1% (N = 85) are continuing to have anal receptive sex without the use of condoms and 38.81 (N = 132) had two or more sexual partners within the last thirty days; and 24.4% (N = 83) had anonymous sexual partners. TR188 TP189 The Minnesota AIDS Media Campaign Consortium (MAMCC) - organizational Approach KAREN A. HECKERT, M.E. MOEN, Minnesota Department of Health, Minnesota AIDS Media Campaign Consortium, Minneapolis, MN, USA. During 1986, the Minnesota Department of Health developed a statewide health education and risk reduction plan to control transmission of HIV in Minnesota. One objective of the plan was to develop a statewide mass media campaign and to evaluate its success. In February, 1986 the Minnesota Poll, (a random statewide telephone survey) demonstrated that 90% of those surveyed considered mass media to be their primary source of AIDS information. To ensure statewide coordination of media efforts, the efficient mobilization of resources and the develOpment of the most effective messages, we developed the MAMCC. The MAMCC is represented by two state public agencies (MN Dept. of Health, Dept. of Human Services), four local public health agencies (Hennepin Co. Comnunity Health Dept., Mpls. Health Dept., Ramsey Co. Health Dept., St. Paul Div. of Public Health), three state and national private non-profit agencies, (MN AIDS Project, MN Medical Assoc., American Red Cross - St. Paul) and one private for-profit agency (MN Insurance Information Center). Marketing data from the statewide MN Poll, the Ctr. for Health Statistics, the MN AIDS Project surveys of youth and gay men guided the development of effective messages. Messages that have been developed promote the elimination of risk and utilization of services. A Twin Cities comunications firm was selected in a competitive process to develop a creative strategic plan and media products for the media campaign. The MAMCC development, the ad agency selection process, the strategic plan, the media products and the evaluation techniques may have application value for other low prevalence states. An Inter- TE190 AIDS: What You Need to Knav: A Teaching Unit for Secondary Schools. ANN BONNER, Seattle-King County Health Department and L. Miller. University of Washington. Seattle, Washington. U.S.A. We developed an AIDS curriculun to enable high school students to make informed decisions about AIDS as a public health issue and to make safer choices in risk—taking behavior. The curriculun covers AIDS epidemiology and projections. etiology, pathogenesis, blood—testing, and prevention. The curriculum can be modified to suit the teaching situation. Depending upon the level of student knowledge and classroom constraints. any of the modules may be used. Assessment of student conurehension can be ecconplished with evaluation momles consisting of learning—check questions and an exam for measuring objective learning. we tested the curriculun on 2&0 eleventh graders. The test results revealed a significant increase in student knowledge, which corresponded with a positive change in students' attitudes about the disease. We conclude that exposure to a curriculun which impact: upon knowledge and attitude will enable young people to make informed public health decisions about AIDS. “3191 Distribution of Free Condoms as a Technique to improve Acceptance ' of Condom Use. ARTHUR STUTSMAN, B.M. Branson, J. Stein, Resource Organization, Baltimore. MD. USA. A survey was conducted to identify factors that might discourage the use of condoms. Respondents frequently cited interference with sensation, lack of familiarity and embarassment when purchasing condoms as important reasons for not trying them. A majority were not familiar with proper use of condoms, and personnel in STD clinics were rarely trained regarding procedures for proper appHcafion and use. A graphic, pictorial brochure with step-by-step instructions for condom use was developed. A sample packet. including the brochure, safer sex informa- tion and condom samples wasdesigned. labeled "A Healthy Gift from HERO." Gay-patronized retailers such as bookstores and gift shops were solicited to distribute these with customer purchases. Additional samples were prepared in a matchbook-cover package design, with the message “Stop Transmission Fluid Leaks" or “Life Preserver“ imprinted on the cover. Each of the sample packets were well received, and proved popular with both retailers and the general public. Samples became sought after, and proved to be an incentive. attracting targeted at-risk individuals to neighborhood edu- cational presentations in order to obtain condom samples. D. Vaughan, Hea|th Education 94 Contact Tracing for STD's : A Review MICHAEL L. REKART, UBC School of Medicine, Vancouver, B.C., Canada TB192 Contact tracing is an integral part of the standard public health approach to the control of sexually transmitted diseases (STD'S). It needs to be con- sidered in the control of AIDS but can only be objectively evaluated when its definition and history are examined. Three distinct types of contact tracing exist. First, 'formal contact tracing' is a system in which specially trained staff interview patients, obtain names and addresses of sexual partners, lo- cate these partners, and offer them examination and treatment. This is the tra- ditional method used for gonorrhea and syphilis. Second, 'simplified contact tracing' refers to a variety of methods by which patients identify, locate swimmemenmmnmnfitmuomsuulwnmmeMMswdfiuny naming them to the health worker. Last, 'conditional contracting' is a sys- tem in which contact information is given to the interviewer in trust and the patient contracts to notify these partners within a specified period of time. If this fails, the interviewer must seek out the sexual partner for assess- ment. All of these methods have clear advantages and disadvantages. Simplified contact tracing is the method usually used for AIDS and HIV seropositivity. N. L. Munson in 1932 was the first to demonstrate that contact tracing was possible and effective in finding new infectious cases of syphilis. This 'sole-leather epidemiology' works as well for gonorrhea and has contributed significantly to the control of both. TP193 The blood donor perspective on false positive test results: The im- ' pact of anti-HIV test procedures A,P.M, LQ§*, M. VONK“, L. ACHTERHOF**. TJ. TIJHSTRA*, T.B.P.M. SUURMEYER", C.TH. SMIT SIBINGA**, * Div. of Medical Sociology, University of Groningen, ** R.C. Blood Bank Groningen-Drenthe, Groningen, NL For confirmation of initial findings on ELISA tests a fresh blood sample is needed, and the donor has to be called back. Of over 97,000 donations tested since May '85, 6A (0.0762) turned out to be false positive. with focused inter- view technique donors (n-30) were asked whether they associated the recall with AIDS or the anti—HIV test, how they handled the information about the test pro- cedure, and what their reactions and feelings were. Results: 19 Indicated to be upset by the recall. The thought of AIDS was mentioned by 17 although immediately rejected as considered impossible for themselves. Only 2 associated the recall with the anti-HIV test and 20 were ignorant of the existence of the test. 18 Indicated to pay hardly any attention to information related with AIDS because they have no risk factors. Ignorance of which tests actually are done made 16 upset by the thought of leukemia and cancer. 13 Associated the recall with their health at the moment of donation, and another 13 were very surprised by the recall because they felt healthy. 20 Indicated to consider blood screening as a very important check on their health. Conclusion: Misunderstanding and anxiety can be relieved by carefully infor- ming donors about meaning and content of donor screening. Information about im- portant and new aspects of AIDS and screening procedures should preferably be included in this general information, rather than be given separate attention. TR194 Assessment of the AIDS Public Information Campaign in the UK HILARY PICKLES and G.Bond*,DHSS AIDS Unit and *Central Office of n ormation, ondon, England. The UK AIDS Public Information Campaign has involved newspaper and magazine advertisements,cinema, radio, street posters. TV and a leaflet delivered to all households. A detailed leaflet and telephone advice services have also been made available. This campaign has been subject to a larger programme of research than any other government-run publicity campaign. In general, this research has shown (1) there was great interest in the subject of AIDS. with high percentages claiming to have seen and taken note of AIDS publicity, (2) the main methods of trans- mitting HIV were widely understood (3) misconceptions, for example as to the dangers of blood donation and transfusion and of casual contact were widespread but diminished over the time of study (4) any claimed recent changes in behaviour were in the desired direc- tion, (5) offence was not caused by the material presented, in spite of mention of matters such as anal sex and drug injecting, (6) there was extensive support for a government-conducted campaign of this sort. TUESDAY, JUNE 2 TE195 Intravenous Dru Abusers Infected with Human Immunodeficiency V rus: Details of Behavioural Patterns over the Period of an Epidemic J.R. ROBERTSON, CAROL A. SKIDMORE, A.B.V. BUCKNALL, J.J.K. ROBERTS, N.B.F. GALLOWAY, C.A. FOSTER, Edinburgh Drug Addiction Study, Scotland Intravenous drug abusers infected with AIDS virus and those apparently non infected were part of a cohort of 250 individuals followed over a 2 year period. Retrospective data was available on 117 individuals 683 men (712) 34 wonen (29%) with a duration of heroin use of 3.6 years (SD 2.28, range 0.2-1h.8). Importantly the length of time of Intravenous drug use to presentation to medical Intervention was 1.25 years (SD 1.43, range 0-7.75). The group had been in contact with the doctors for 12.8 years (SD 8.h+, range 0.1-28.6). Case record search and detailed Interview data was used to validate and corroborate the information as well as the subjective analysis of physicians with clinical reSponsibiIity. Results demonstrate a peak of heroin use in l98l-1983, 60% of study group commencing use during these years. Subsequent heroin use was subdivided into Abstinent, Dependent and Non-Dependent use, most individuals demonstrat- ing change between these patterns of behaviour every 0.108 years. As expected the total number of episodes correlated with duration of use (r=0.h25, p< 0.001). In the total of A995 months of heroin use 39% was spent in abstinence, 10% in non-dependent and #82 dependent use. No correlation between groups and HIV seropositivity was demonstrated. Conclusion: Drug users demonstrate varying patterns of use amongst individuals over time and in a group. T2196 Intergrating Positive Attitudes and Healing with the Expression of Painful Emotions and Dying in a Client Support Group JIM GEARY, Executive Director, Shanti Project In facilitating a support group for people with AIDS/ARC group leaders and members often find themselves in conflict regarding some members' desire to maintain a positive attitude and other members need to express depression, grief and/or concerns regarding dying. These needs can also be present con— currently in any one individual. Often members will not return to group because they find the group process too depressing or positive to the point where they feel unable to deal with difficult emotions. Having facilitated a group for people with AIDS/ARC for 5 years, I have learned ways to support certain group members in maintaining a positive attitude, while assisting others dealing with painful emotions. These methods have resulted in a more intergrated approach to facing one's illness. I have found that when people realize that they can express strong emotions, yet still maintain an overall positiveness that this empowers them to handle whatever emotions they feel, rather than be controlled my them. I have concluded by the success of my support group, measured in terms of longevity of attending members, that both metaphysical as well as more common- lly accepted approaches to dealing with illness can be combined and mutually supported for the benefit of everyone. Men With isolated Thrombocytopenic Purpura - The Impact of Psycho-Physiological Intervention on Platelet Count TP.197 Inge B. Corless* D. Abrams**, E. Biglieri**, M. Dodd** *University of North Carolina, Chapel Hill **University of California, San Francisco, California A psychophysiological intervention composed of relaxation, imagery and therapeutic touch was investigated as to its effect on platelet count, helper: suppressor ratio, and adrenal function, in eight males with Isolated Thrombocytopenic Purpura. Individuals in the experimental group received a sixty minute psychophysiological intervention thrice weekly supplemented by an audiotape three times per day. After the five week intervention period participants used the audiotape alone. In a delayed start design, control group patients also received the intervention. This paper reports the psychological findings and their relationship to hematological and immunogical status. Control group patients exhibited an increase in tension and depression as measured by the Profile of Mood States from the baseline measures to the time of intervention. This same pattern was not observed in the experimental group. The experimental patients who showed decreases in tension, depression, anger, confusion and fatigue in the first five weeks exhibited further gains in the next five weeks. A trend was observed between decreases in depression and tension and an increase in platelet counts in two patients. Only one of the eight individuals had a normal H:S ratio. Increases and decreases in these ratios over the ten weeks were not remarkable. Five of the eight men had adrenal responses requiring further evaluation. 95 T2198 Delivery of Psychosocial Services in a non-urban area using a model of Volunteer Efforts. MARGARET NICHOLS*,S. FLACK,* Hyacinth Foundation, New Brunswick, New Jersey AIDS Health-care experts generally agree that volunteer-based psychosocial support programs such as Gay Men's Health Crisis in New York and Shanti Project in San Francisco can deliver services in a highly cost-efficient and successful manner. However, such programs have been instituted primarily in urban areas. Hyacinth Foundation is one of the few programs operating in a suburban/ rural setting as well as in urban centers. This paper describes the different issues that face service providers in suburban areas including such topics as: l) dealing with geographic distances and the need for decentralized programs; 2) handling the generally greater stigma and shame that suburban AIDS patients feel and the concammitant need for extreme confidentiality, even secrecy, that these patients require; dealing with families of origin of AIDS patients in suburbia. We will discuss the problems each of these issues present as well as potential solutions. TE199 Multidisciplinary Planning for the Psychosocial and Legal Needs of Persons with AIDS and their Families LAUREN GORDON, csw, c. ZUCKERNAN, JD, Montefiore Medical Center, Bronx, NY, USA Since 1985, social workers and attorneys, as members of a multi- disciplinary AIDS team, have jointly addressed psychosocial-legal problems of approximately 1 out of every 3 persons with AIDS and their families followed by the team. Timely and sensitive planning for the patient's decline and death and the continued lives of fa- mily members is necessary. Our clinical experience with a predominantly minority, both male and female, AIDS population, has identified 7 major issues affect- ing the nature of future planning and the options for legal inter- vention: 1. Relative youth of patients; 2. Existence of minor chil- dren or others financially and emotionally dependent on patients; 3. Lack of economic resources among patients and families; A. Emo— tional shock and chaos following diagnosis; 5. Time limits imposed by the illness; 6. Societal bias attached to patients (due to di- agnosis, ethnic or racial status, drug abuse history or sexual or- ientation); 7. Nature of living arrangements (unconventional but accepted patterns of extended families which confuse traditional legal responsibilities). Early recognition of specific problems requires novel and flex- ible uses of such legal mechanisms as durable powers of attorney, wills and child custody and guardianship procedures. Advance legal and social planning provides security and control to patients oth- erwise overwhelmed by their illness. Ongoing assistance offered to families helps survivors in coping with the loss of loved ones. TRZDU Behavioral. Immunological and Biochemical Patterns in ARC and AIDS. W V. I. KVITASH“. ‘San Francisco State University, wMedical Research Institute of San Francisco at Pacific Presbyterian Medical Center, San Francisco, CA USA Potential markers for predicting development of AIDS were studied in 33 men with ARC. Thirty-eight healthy controls and I 1 AIDS patients were also evaluated. Seven behavioral parameters (medical events. general well-being. psychological well—being. nutrition. tobacco use. alcohol use, physical activity) 6 immunological and 9 biochemical parameters were analyzed with the assistance of a computerized technique permitting pattern cognition and graphical representation of relationships among these 22 variables. During 30 months of follow-up, 4 men with ARC developed AIDS, IS remain healthy or have not progressed with additional ARC symptoms; 14 men were lost to follow-up. No healthy controls developed ARC or AIDS. AIDS-resistant ARC patients had a higher cholesterol (173.3). HDL (45.0). T4/T3 ratio (0.78) and alcohol score (80.3) compared to the pre-AIDS ARC patients (149.5). (30.0). (0.31). (70.5). Although no single variable permitted discrimination among AIDS-resistant and pre- AIDS individuals with ARC. composite computer generated patterns of multiple intersystem regulatory abnormalities at the time of initial presentation provided clear separation without overlap. We conclude that definitive early identification of pre-AIDS individuals among ARC patients is possible using routine clinical laboratory tests when combined with behavioral data. TUESDAY, JUNE 2 TP201 Predictors of chronic psychosocial disturbance arising from the ' threat of HIV infection: Lessons from Heterosexual, Bisexual and Homosexual Worried Well patients. DAVID MILLER, The Middlesex Hospital Medical School, London, England. Twenty patients presenting with high-level psychological distress in response to the threat of HIV infection were assessed on 16 psychosocial variables. All presented conspicuous management difficulties. There was a striking consistency in the presenting and background histories of patients within this group. These consistencies concerned the appearance of misinter- preted somatic features, numbers of negative antibody tests undertaken, difficulties in sexual adjustment and self-acceptance of sexuality, poor social integration, previous psychiatric/psychological history, level of physician attendance, problems of sexual expression, previous low experience of sexually transmitted diseases, obsessive-compulsive disturbances, anxiety, depression and suicidal planning. The consistencies found in this group enable future managment requirements in this and other groups to be predicted. In addition, this analysis provides a measure of the impact of the threat of HIV in sections of low—risk heterose- xual communities. It appears that 'worried well‘ persons with the lowest levels of objective risk frequently require a much larger amount of clinical involvement and present with a greater threat for suicidal activity than people from other groups. This is due to their higher levels of social isolation, psychological vulnerability, sexual maladjustment and guilt. Social Support in gay men with the Acquired Immunodeficiency Syndrome (AIDS). Auburn University School of Nursing, Auburn, AL 36849 TR202 BECHTELl G. A. Social Support is a core requirement for human survival and it assists an individual in recovering from a major life crisis. Because most individuals diagnosed with AIDS are already partially Isolated from society due to the stigma attached to homosexuality, social support networks have limited functional ability. The problem of the study sought to determine if differences exist in social support systems between gay men diagnosed with AIDS and those at high-risk for developing AIDS. The sample consisted of 67 gay men from a metropolitan area of a conservative southern state. Thirty-six of the respondents were diagnosed with AIDS and 3i at high-risk for developing AIDS based on their sexual lifestyle. Each participant was given the Norbeck Social Support Questionnaire (NSSQ) which measures both social support networks and functional support systems. The Mann Whitney U-Test showed no significant difference between groups in either subscale of the N850. However, social network scores were far below the "norm" although functional support scores fell within normal ranges. Social support scores from both subscales were significantly correlated with income for individuals diagnosed with AIDS and perception of health status for individuals at high-risk for developing AIDS. Neither support subscale was significantly correlated with the amount of support lost although both groups reported losses from lovers, friends, and family. The study suggests that immediate intervention to develop and encourage social support systems is not as important as the maintenacne of support systems which are already In place. T2203 AIDS Education In Medlcal and Nursing Students: Knowledge and Attitude Correlates HARVEY BARTNOF MD*, Jeffrey Mandel‘, Margaret Grade‘. Leonard Zegans‘, Barbara Faltz“, at al, ‘UCSF School of Medlclne, *‘UCSF School of Nurslng, San Franclsco. CA Health care provlder students are often thrust Into cllnlcal environments wlth HIV-Infected persons prior to havlng adequate knowledge about AIDS or HIV. In attempt to obvlate this problem, a thlrteen hour muItIdIsclpIInary survey elective course on AIDS-HIV was deslgned at UCSF and led to an enrollment of 139 medlcal, nursIng, and pharmacy students. Frlor to the fIrst lecture, students were asked to complete an anonymous questlonnalre on AIDS knowledge, attltudes. and personal demographics to determine the level of knowledge about AIDS, and to ascertaln any stlgmaphoblas and demographic correlates whlch mlght detract from optimal cllnIcal Interactions wlth AIDS and ARC patlents. An ldentlcal post-course questlonnalre will be adnlnlstered In March, 1987 to ascerteln any changes. Fro-course questionnalres lndIcoted that 261 of medloal students (HS) thought AIDS could be transmitted by mosqultoes and 181 belleved AIDS could be transmltted by sweat or urine. Self IdentIIIed gay/bI/Iesblan (SIGEL) nurslng and pharmacy students achleved sIIghtly hlgher knowledge scores (975 and 881 respectlvely) than dld theIr heterosexual counterparts (HC) [871 and 7511 whereas SIGBL and heterosexual HS scored equally high (885 vs. 851). Interestingly. slgnlflcantly more SIGEL medlcal and nursing students (60! and 1001) agreed or strongly agreed (AOSA) they had a lot of knowledge about AIDS than dId thelr HE (IS! and 281 each). 18-291 of all students AOSA that hospltal employees should be allowed to refuse to care for persons wIth AIDS (FHA). 5-3}! of all students would prefer to avold caring for FHA. Generally. there were low rates of homophobla and ethnlphobla. Post-course questionnalres wlll be completed In March I987; those data will enable us to ascertaln pre- and post-course correlatlons between demographics, knouledge, and attltudes. Verbal feedback to date Indicates that AIDS educatIon of student health care provlders further decreases stlgmaphoblas and maxlmlzes knowledge on AIDS and HIV. In turn, thls llll optImIze patIen1 care. 96 TR204 The Response of Philanthropy to AIDS: A Survey of Private Giving Trends Between 1982 and 1986 to AIDS—related Issues and Implications and Considerations for Future Support GEORGE MARSHALL WORTHINGTON, Worthington and Associates Worldwide, New York City, New York Most philanthropy is an unimaginative, dutiful, and largely dubious process. Nearly half——$21.7 billion——of America's philanthropic contributions in 1984 went to religion; another $7.6 billion went to health care, nearly one quarter of which was used for hospital consruction--and this in a country with a sur— plus of hospital beds. In general, projects involving social change issues of any kind-—research, conferences, publications, legal suits, large "pilot pro- ject" service organizations, and occasional grassroots groups—-got less than 2.8 percent of the total. Even the Ford Foundation, considered the most adven- turous of the large foundations, gave only 8 percent of its money to projects concerned with social issues. With respect to AIDS, in particular, the picture is considerably less optimistic by comparison. But the situation is changing. Oral abstract will present a complete and current information survey on fi- nancial support for AIDS education, research, and related fields with emphasis on foundations and corporate giving programs. The survey will include the out- comes and follow—up to the five Regional Associations of Grantmakers which held meetings on AIDS in 1985. Presentation will include information on foundations and corporations which have expressed an interest in AIDS with emphasis on their giving interests: research/treatment; services; public policy, communityA and public education; housing and hospice programs; advocacy and civil rights for persons with AIDS. Information will also be provided about grants made-to- date, including foundation or corporation with amounts, grantee, project or purpose. Also included will be guidelines for grantmakers and grantseekers, in— cluding where support is needed plus a suggestive list of funding opportunities. T2205 HIV SEROPOSITIVE MOTHERS AND THEIR BABIES — DELIVERY OF HEALTH CARE. g M95, S Davidson, RP Brettle, City Hospital, Edinburgh. An epidemic of HIV began in Edinburgh amongst heterosexual intravenous drug misusers in August 1983 and had reached 50% seropositivity by 1985. Only 40% of the individuals are currently abusing and one third are female. with the introduction of the HIV antibody test in October 1985 families with one seropositive individual and newborn babies were detected. Previous experience of this group in delivering health care had revealed default rates of 30—40%. On the let January, 1986 we established a separate hospital based out patient service specifically for at risk mothers and babies. This involved: 1) the joint attendance of mother, baby and/or father for health care assessment, counselling and education. 2) the service was provided by a consultant paediatrician in community health, a midwife/counsellor and a consultant in Infectious Diseases. 3) a liaison health visitor coordinates the care in the community and the referrals from 4 obstetric services. 4) where necessary the problem of non attendance has been overcome by home visiting. To date 38 families have been enrolled in this service which consists of 3 monthly assessments. Twenty—five infants were born to 24 seropositive mothers, of whom 58% attend hospital regularly, 42% consistently utilise home visits. One family needed home visits to establish contact and encourage hospital visits. No families have been lost to follow up to date but despite intensive counselling and education 2/24 or 8% of the mothers became pregnant and required terminations. T2206 A Conceptual Model for a Transitimal Se1f~Help Residence for IVDA with AIDS/ARC J.PERRY, G.K.‘DRIGJEZ, L. ROI'KIEWICZ, SNOW, New Jersey State Dept. of Health (NJSDH), Trenttn, NJ. housing is needed for AIDS/ARC patients who are anullatory and able to provide self—care but wrmntly lack stable 11113in and thus, appropriate discharge and referral frun inpatient settings. The NJSDH has identified an urgent need for such a resource in the Newark/Jersey City area, whezenostAIDS/ARCoasesarerelatedboIvdzugamse. Itis izedthatoost—effectiveandtnmmcazecanbestbepmwidedina stall—scale residential facility that tosses 20 perscns reimbursed at a per diem rate through state funds. To facilitate negotiaticns with local ounnmiity groups, a conceptual model was developed. Resource develcgnent is based cn the nature of the disease and the risk group to be served and is structured as part of a continuum of post-mspitalizatim care. Oarpormts of the model include eligibility criteria, staffing patterns and job respcnsibilities, daily activity schedules, rules and regulations geared toward self-care, requirements for hardtoring and to the funding source, and a per diem reintxuzxmemt rate lower than that for acute long-term care or residential drug treatnatt. A flow chart illustrates potmtial patient transfers mag alternative levels of care. This process is facilitated by case management. TUESDAY, JUNE 2 TP.207 The Attitudes and Knowledge of Health Care Professional Working with Patients with AIDS and How They Impact on Their Professional Behavior. WILLIAM g; NELSON, W. C~, HOLZEMER, M. O'ROURKE, San Francisco General Hospital. San Francisco, California U.S.A. A survey was condficted in 3 cities of the United States. The survey was a post—test for 3 workshops on AIDS given in Anchorage, AK, Eureka, CA and 50. San Francisco, CA. Sample surveyed consisted entirely of registered nurses. These nurses had worked with as few as 0-1 patients with AIDS, to 10 pts with AIDS. Academic preparation of nurses was varied. Not all nurses performed bedside care. Majority of respondents were caucasian women. A majority of nurses received their nursing education in the 3.3. Purpose of the pilot study was twofold. We were piloting a new survey tool based on the works of Rubin & Peplau (1975) and Herek (1984). Main thrust of the pilot study was to look at nurses‘ responses to attitudinal/knowledge questions and compare those responses to questions which required a professional judgment. The null hypothesis states that essentially no differences exist between nurses in outlying areas and those closer to a major metropolitan area where AIDS was more commonplace. Early analysis of the data show: 1) nurses are open to learning about AIDS and dealing effectively with those patients, irrespective of how they may feel about homosexuality or I.V. drug use; 2) that nurses are not as homophobic as may have previously been thought; 3) that nurses work effectively with AIDS irregardless of how much exposure to AIDS the nurses have had. TP208 Hospital costs of patients with AIDS in Richmond, Va. ' L.KAPLOHITZ. J.TIPPLE, J.TURSHEN. P.MYERS. A.BERRY, L.STALOCH, Medical College of Virginia, Richmond. Virginia. Inpatient hospital charges were analyzed for 52 AIDS patients (pts) with 98 hospitalizations(hosp) between Oct. 1983 and Dec. 1988 (range 1 to 6 hosp/pt): All were hospitalized at the Medical College of Virginia. the major facility for care of AIDS pts in central Va. Risk factors for AIDS included gay male 31. IV drug use 14. gay and IV drug 2. blood 1. heterosexual contact 4. Two were females (mean age 29.5 yrs) and 50 males (mean age 34 yrs) with 16 white. 35 black and i hispanic. Reasons for hosp were PCP 41. other opportunistic infections 25. bacterial infections 8, KS 2. lymphoma 1. encephalopathy 10, malnutrition or fever 9, other 2. Analysis by payor in 1986 dollars is shown: Payors Hosp Hosp Avg SD Avg Avg charge 8 Days L08 L05 charge per dien Blue Cross 16 212 13.3 6.8 $9831 5686 Commercial 19 337 17.7 15.5 $16027 3845 Corrections 14 245 17.5 9.1 $14991 $909 Medicaid 19 266 14.0 16.7 $9669 5735 Self pay 30 404 13.5 12.8 310365 $1019 Total 98 1464 14.9 13.0 $11869 3860 Five hosp were over 34 days including 3 commercial (52d.50d,44d). i medicaid (73d). 1 self pay (62d). There is no statistical difference in charges or LOS among the payor groups. Room. lab and pharmacy comprised 68.4: of charges, ICU 7.4x. radiolozy. ER. OR and ancillary 14x, and diagnostic studies 10.2x. These charges are lower than initial estimates of hospital care of AIDS. TRqu Designated AIDS Centers/AIDS Intervention Management System (AIMS) IRA FELDMAN, R.F. HUMMEL, JUDITH SIMMONS, M.D., NYS Department of Health, Albany, NY In January, 1986, New York State amended pertinent regulations in order to allow for the designation of acute hospitals as AIDS Centers for the care and treatment of AIDS patients. The Designated AIDS Center concept is based on a continuum of care/case management model designed to meet and/or arrange for all levels of care and needed services required by AIDS patients. This model will allow for increase access by persons with AIDS to essential health care and community resources so that AIDS patients are able to maintain the quality of their lives in a home environment as long as possible. In conjunction with the AIDS Center process, New York State solicited competitive applications from qualified organizations for the design, implementation, and operation of an oversight system to review the performance of the comprehensive AIDS Centers, conduct a comparative review of AIDS patients, and ensure that appropriate standards of utilization review, quality assurance and case management are established and met. This oversight system is referred to as the AIDS Intervention Management System (AIMS). AIMS will centrally coordinate the retrieval of data from the multihospital treatment of AIDS patients under the case management, discreet unit model. Information concerning inpatient/outpatient services and costs as well as diagnostic and demographic data will be retrieved and analyzed in order to provide new information concerning the impact of AIDS and HIV related illness on the health care delivery system. 97 TP210 Survey of United States Nursing Schools' Guidelines/Policies on AIDS ' CHERYL L. BOWLES, V.L. CARWEIN, Department of Nursing, University of Nevada, Las Vegas. A descriptive survey of 242 NLN accredited schools of nursing was conducted to identify guidelines and methods used to deal with both student assignment to AIDS clients and students who are antibody positive or diagnosed with AIDS. In the absence of existing guidelines responses were based on personal thoughts or feelings. Results indicated 95% of the schools of nursing have no guidelines for deal— ing with infected students, 76% have no guidelines for dealing with student assignments to AIDS clients and 492 have no plans to develop guidelines. Thirteen percent felt HIV antibody testing should be required of all nursing students and 81% disagreed. while 66% responded that another assignment would be made if a student refused to care for an AIDS client, 45% added "other" comments, primarily student conferences and further AIDS education. In response to dealing with antibody positive students who are not ill, 84% felt students should remain in theory and 64% in clinical. Regarding who should know the student is antibody positive, 62% felt the student health center, 35% only nursing faculty in direct contact and 512 the nursing school administration. When asked about students diagnosed with AIDS, 79% would allow theory attendance while only 31% would allow clinical attendance. Regarding who should be notified, 67% indicated the student health center, 41% only nursing faculty in direct contact and 61% the nursing school administration. Results demonstrated few schools of nursing have existing guidelines, many have no plans to develop them and uncertainty abounds in the resolution of ‘ these issues. "’2“ HIV Infected Patients with Pulmonary Tuberculosis: for Health Care Workers (HCHs) $.0FFUTT, ROBERT E. NADELMAN, G.P. WORMSER, NY Medical College, Valhalla, NY. Recently, the associat1on of TB with HIV infection has been noted. Since TB is potentially communicable to chs and since respiratory isolation is not rou— tine for patients with HIV infection, we reviewed our experience with patients who had both infections. M cobacterium tuberculosis infection was documented by culture for 35 patients at our hospital between 1/1/85 and 12/31/86. Seven- teen of 18 of these patients who were tested for HIV demonstrated presence of serum antibody. Nine of these 17 patients (53%) had extra-pleural pulmonary TB (PTB) with or without other + culture sites. Six of 9 patients had sputum smears + for AFB. Respiratory isolation was instituted on admission for 4/9 (44%) of the patients, but in the other 5 (56%) PTB was not initially-suspec- ted. Time to institution of isolation ranged from 2-41 days with a mean of 8 days. Delay in instituting respiratory isolation resulted from a lower index of suspicion for TB in HIV infected patients who were initially believed to have had an alternative diagnosis. No patient had cavitary disease and only 2 had upper lobe infiltrates. Other CXR findings included 2/9 patients with only lower lobe infiltrates, l with only adenopathy, 1 with apical scarring, I pleu- ral effusion, and 2 with a normal CXR. Six patients with PTB had a + PPD. TB's resurgence in the HIV infected population has been characterized by ex- trapulmonary and non-classical infection. The frequently atypical CXR and the occurrence of skin test energy may mask the diagnosis of PTB in the HIV infec- ted patient. The lack of early institution of respiratory isolation in these patients may pose an increased risk of transmission of TB to HCHs. A high index of suspicion for TB in HIV infected patients will be essential in preventing nosocomial outbreaks of TB. Risk of Exposure 113212 Orthopaedic Surgeons' Attitudes and Practices Concerning Treatment of Patients with Human Immunodeficiency Virus (HIV) Infection PAUL ARNOH, L. POTTENGER, C. STOCKING, H. DE LEEUN, H. SIEGLER. University of Ch1cago, Chicago, IL. Concern regarding a possible occupational risk of acquiring HIV infection has made some health care workers reluctant to treat AIDS patients and may in- fluence surgeons' willingness to operate. To assess attitudes and practices of a group of surgeons that treats young and middle aged males, we conducted a questionnaire survey of all orthopaedists in the five cities with the most AIDS cases. Topics included experience, knowledge of HIV transmissibility, precautions during surgery, HIV testing of patients and surgeons, and ethical obligations of surgeons. Questionnaires were mailed during March-July 1986 and were completed anonymously by 325 of 510 orthopaedists. In the previous year, 142 (43%) had examined or operated on an HIV—infected patient, and 90% of re- spondents who evaluated HIV—infected patients for surgery chose to operate. Decisions to operate appeared not to be based on hospital requirements, per- ceived ethical obligations, or knowledge of HIV transmissibility. About half of the orthopaedists who operated considered HIV to be more transmissible than it is. Most orthopaedists felt they had the right to require preoperative HIV testing of all patients (7l%) and high risk patients (85%), but such testing was ordered infrequently. Forty-three percent of orthopaedists felt patients have a right to know if their surgeon is HIV-positive, and 5l% felt restric- tions on the professional activities of infected surgeons were necessary. Al- though orthopaedists reserved broad rights for themselves, they almost always were willing to treat patients with HIV infection. TUESDAY, JUNE 2 T2213 Psychological problems in nursing patients with AIDS Seidl,0.,Goebel,F.-D.:Medizinische Poliklinik,University of Munich,West Germany Nursing the patients with AIDS causes a lot of problems which are not comparable with those in nursing other patients with a terminal illness.Health—care personnel experiencetmany sources of stress leading to an emotional exhaustion. To understand the emotional reactions and to help the staff members we performed "training cum research“groups(Balint) once a week over a half year period. In the first months an imposing feeling of hostility against the patients with AIDS predominated.They were experienced as self— willed,demanding and conceited in a strong difference to other patients.The nurses had difficulties to assert themselves,and if they could,patients raised the feelings of not being a good nurse. within the hospital nurses felt themself stigmatized because of nursing stigmatized patients with a stigmatized illness.The fee— lings and the reactions could be interpreted in the group-process as a consequence of the more or less unconscious negative attitu— de to the patients on one side and the identification with the mostly young,intelligent and alert homosexuals on the other side. The perception,that nearly all patients shall die let to interpre— tation of all their wishes as last wishes,lending to the difficul— ty to say "no".The more the motives of nurses became conscious,the more stress in nursing was reduced. "Training cum research" groups seems to be a possibility to gigam$figstaff stress,especially the chronic professional stress TR214 A Survey of Residency Programs for Persons with AIDS M. Monroe Wright, M.Div., S.T.M., the United Methodist Church, Branford, CT. Lack of alternative housing represents a growing financial and social problem within the context the the AIDS epidemic in the US. For hospitals there is the accumulation of "Administrative Necessary Days“ and for Persons with AIDS (PNAs) there is the burden of institutionalization. Various urban centers have estimat- ed that 30% of PNAs lack appropriate alternative housing. There are several causes: patients' ostracism by family, roonmates, lovers; evictions; financial straits and refusal of nursing homes and hospices to admit. This paper is a survey of eight urban residency programs for PNAs. Half are in areas with high concentrations of PNAs. Various models are presented: small group hones, "hotels," foster homes and rent subsidies. The common thread is that while no direct health care is provided by the sponsoring organizations ex- tensive psychosocial and spiritual support is rendered directly and health care is coordinated from hospital discharge planning through to Visiting Nurse ser- VlCeS. Emerging issues include IV drug abusers and neurological/physiological limi- tations of residents. Thus there is a need for an increase in supportive ser- vices and direct health care services. The first such programs have garnered ex- tensive support from the Gay conmunity and Federal demonstration grants. Future needs demand more through planning at all levels. The PNAs residency programs' MmcwewwmwpmfimsamuefiufiwahumfiwtommMCMwHflnm tion and an enhanced psychosocial/spiritual environment. 113215 [I‘Tngc/ixiRgg Utilization of Services by Families of Children with MARY BOLAND, E. CONNOR, P. EVANS, J. KERESZTES. S. MORRISON, J. OLESKE Chi dren's Hospital of New Jersey & UMD-New Jersey Medical School. Newark, NJ In 50 families with 57 children with AIDS/ARC, one or both parents are in- fected with HIV. Maternal risk factors were: intravenous drug use (28/50), sexual partners with AIDS or at increased risk for AIDS (16/50), maternal blood transfusion (3/50), Haitian (2/50). and no identified risk factor (1/50). 42/57 children reside in a single parent family headed by a woman. 2/57 chil- dren were cared for by their fathers. l7/50 families were known to family protective services agencies prior to the diagnosis. HIV infection is a family illness. 10/57 children have at least one parent who has died from AIDS. Only 3/36 parents received regular medical care. The remainder (33/36) received episodic care for acute symptoms. Illness in a parent decreased the amount of physical and emotional energy available for parenting. The combination of drug use. poverty and illness stressed an al- ready weakened family unit. Hospital based care services were poorly utilized. Initial home visits by a nurse and social worker lead to the development of a relationship with the family..Subsequently, 32.57 children received the following services in the home: nursing care (32/32); homemakers and home health aids (6/32); physical therapy (9/32). and speech therapy (4/32). The family with HIV infected menbers deals with nultiple stresses on a daily basis. Assuring continuity between hospital and home while providing care in the home can result in improved utilization of services in both settings. 98 “3216 Treatment of AIDS-related Kaposi's Sarcoma (KS/AIDS) by Alpha-2- reiombinant Interferon and Bleomycin. L.J. couotnc , S.MATHERON3, M. JANIERl, P.M. GIRARDZ, M. SELIGMANNl, J.P. CLAUVELl. 1 : Hopital Saint-Louis 75010 Paris. 2 : Hopital Claude Bernard W—FRANCE- The efficacy of recombinant leukocyte A interferon (Roferon) treatment of KS/AIDS has been previously evaluated. We have showed response of KS/AIDS to bleomycin alone (Second Intern. Conf. on AIDS. Paris 1986). In a pilot study, we evaluated Roferon in combination with bleomycin. Roferon was given I.M. at 18 Mu daily for one month and was continued at the same dose three timesweekly A slow continuous infusion of bleomycin was given I.V. at 6 mg/m2 daily for 3 days each month. Treatment was continued unless tumor progressed. In october 1986, the first 9 patients were enrolled in this prospectivestudy All patients were homosexual men with disseminated KS. No patient had received treatment for KS. Preliminary results indicate that 2 had acomplete response, 3 a partial response, 3 a stable disease. One patient developed Pneumocystis carinii pneumonia. Final results will be presented on all the patients treated for more than 3 months. TP217 INHALED PENTAMIDINE AS EXCLUSIVE THERAPY FOR PNEUMOCYSTIS CARINII PNEUMONIA (PCP) IN THE ACQUIRED IMMUNODEFICIENCV SYNDROME (AIDS). J.A. Golden, H.Hollander, J.E.Conte,Jr. University of California,San Francisco, CA. The treatment of PCP is associated with side-effects in over 50% of AIDS pts. We therefore assessed the efficacy of inhaled pentamidine (P) in AIDS pts with mild PCP (defined as P02>60mn Hg). Pts inhaled P (4 mg/kg) daily for 14 days by nebulization (”Ultra Vent," Mallinckrodt, St.Louis). P levels by HPLC were assessed in bronchoalveolar lavage (BAL) and plasma. Nine pts were entered into they study. Six pts favorably responded to inhaled therapy with resolution of dyspnea, fever, and improved chest x-ray and arterial blood gases. One pt failed after 5 days of inhaled P; two pts became ineligible for the study after less than 48 hrs when they clinically deteriorated and were no longer consider- ed mild PCP. There were no serious adverse effects of inhaled P although 2 pts had P-related cough. Inhaled P resulted in P base concentrations (see table) in BAL that were higher and plasma levels significantly lower than levels in our pts treated with intravenous P (DAL P level 7.15:5.3 ng/ml; plasma level 286:}71 ng/ml) consistent with the efficacy of inhaled P and lack of adverse effects in this study. Inhaled P should be farther investigated Pt # P1 Concentration in BAL (ng/ml) ng Plasma (ng/ml)A 1 N02 - 3.1 2 55.3:17.1 1 14.7 3 28.6110 4 16.9 4 66.8116 3 o 5 16.817 . 3 1 2.5 6 30.61215 14 32.8 1. Mean 1 SD; 2. Not done; 3. day(s) of therapy prior to BAL; 4. peak concentration measured post inhalation, day 1 TP218 Use of Imuthiol (Diethyldithiocarbamate, DTC) in ' Symptomatic HIV Infection. GARY W. BREWTON*, E. HERSH**, P. MANSELL*, A. RIOS', J. REUBEN*. 'Univ. Texas System Cancer Center/Institute for Immunological Disorders, Houston, TX **Univ. Arizona Cancer Center, Tucson, AZ To determine whether Imuthiol improves clinical and immunologic status, we studied the drug in symptomatic AIDS and ARC patients (pts). 4 pts were stratified and randomized to receive either 200 mg/m IV weekly for 4 months or no therapy, followed by crossover to the opposite arm for an equal period. Both groups have been followed with the same clinical and immunologic para— meters, and all pts had evidence of severe immune deficiency at entry. No significant toxicity has been observed. Analyses of results from the first 4 months prior to crossover indicate that treated pts show a trend towards reduced progression (p=.231) and are significantly more likely to show improvement in symptoms (p=.002) and reduction in lymphadenopathy (p=.005) than untreated pts. one treated pt each showed disappearance of marked spleno— megaly, hairy leukoplakia, and intractable perianal monilia. one pt with Kaposi's sarcoma confined to lymph nodes showed partial histologic remission. No significant changes in lymphocyte surface markers, lymphocyte blastogenesis, or skin test reactiv— ity were seen. These results indicate a possible role for immunorestorative therapy in symptomatic HIV infection. Double-blinded, placebo- controlled studies are under way to confirm and extend these findings. TUESDAY, JUNE 2 TP219 Use of High Dose Oral Ketoconazole in AIDS patients for Prevention ' of Relapse in Cryptococcal Meningitis. TIMOTHY P. MESS, WK Hadley CB Wofsy. San Francisco General Hospital, San Francisco, U.S.A. From April 1985 to December 1986, 35 patients with cryptococcal meningitis (CM) were seen at SF General Hospital. 22/35 patients (63%) completed 6-8 weeks of induction treatment with Amphotericin B with or without S—FC. 13 died during induction. Because recurrence is high (30—60%), an open study with high dose (lOOOmg) oral ketoconazole (KCZ) was begun in June 1985 for patients who had completed an induction treatment with Amphotericin B. 20/22 patients who completed induction were offered KCZ prophylaxis, a demented patient and a non- compliantpatient were excluded. 15/20 eligible patients chose KCZ. Of the 15 patients who received KCZ. 7 are still alive without evidence of relapse, range 4-11 months post diagnosis of AIDS and CM. 6 patients have died with a range of survival post diagnosis of CM of 6-11 months (median 7.5) and a range of survival post diagnosis of AIDS of 8-14 months (median 8.5). One of these patients relapsed after 5 months of KCZ therapy and died 2 months later due to active CM. One had an excellent clinical response during 4 months of KCZ and died 1 month after discontinuing KCZ. The other 4 deaths were unre- lated to CM. One lost to follow-up was still free of CM after 7 months of KCZ. 2 patients stopped KCZ secondary to toxicity. One stopped KCZ after 2 weeks due to a )10-fold increase in LFT's and died 2 months later. The other stopped KCZ after 3 months due to abdominal pain and died 5 months later without evi— dence of relapse. 3/13 remaining patients had mild nausea. MIC's to KCZ were available on 13 patients with a median value of 1.56ug/ml (range 0/39-3.l3). 12 serum KCZ levels on 8 patients were available with a median value of 3.79ug/ml (range 2.24-15.0). CSF KCZ levels on 2 patients failed to detect KCZ Only 1/12 (8.8%) patients had evidence of CM relapse while on KCZ. Whether KCZ is as effective or as toxic as weekly Amphotericin remains to be studied. T2220 D-penicillamine(DPA) Treatment for Lymphadenopathy Syndrome (LAS) and AIDS-Related Complex (ARC) DAVID M. PARENTI*,R. SCHEIB*,G. SIMON*,P. CHANDRA**,P. SARIN***,R. SCHULOF*, *Ceorge Nash. Univ. Med. Ctr..wash.,DC. **Frankfurt Univ. Med. Sch., Frankfurt, West Germany, *** Ncl.Bethesda, MD. DPA has been shown to inhibit HIV replication jg vitro. We assessed the clinical, virologic and immunologic effects of 3 different daily oral regimens of DPA in 24 HIV-infected homosexual men who had: (1) HIV isolated from peripheral blood mononuclear cells (PBMC), (2) T4/T8 < 1.0. (3) absolute T4 loo-SOO/mm . and (4) depressed lymphoproliferative responses (LPRs). 19 patients had LAS, 5 had ARC. 10 PTS received oral high dose (H0) DPA (2 gm) for 2-6 wks. 7 were treated with low dose (LD) DPA (0.5 gm) for 12-18 wks. 7 PTS are receiving intermediate, intermittent dose (ID) DPA (l gm). alternating 4 weeks on drug with 4 weeks off. One PT each in the HD and LD groups stopped therapy because of a drug induced skin rash. Therapy was discontinued in 8 HD, 2L0 and 2 ID PTS because of a decrease in T4 or LPR of 2 50%. HIV expression was assessed by measuring reverse transcriptase activity and by detection of p17 and p24 antigens in PHA-activated PBMC co-cultured with H9 cells. HIV expression in LD PTS was unchanged whereas all HD PTS had reduced HIV expression. Complete inhibition was seen in 3/5 HD PTS who received DPA for 6 weeks, without re-expression for at least 6 weeks after stopping therapy. Two patients treated for at least 4 weeks had detectable serum p24 antigen before treatment which decreased by 20% and 60% respectively with treatment. Reversible depression ( 2 20%) of T4 counts was seen in 5/10 HD, 4/7 LD, and 4/7 10 PTS; depressed LPR ( 2 40%) in 7/10 HD, 2/7 LD, and 2/7 ID PTS. DPA has promising in-vivo anti-HIV activity, but further study is needed in order to define a regimen which both inhibits HIV replication without depressing_T1cell numbers or function. TP221 Fanaidan pnophylaxid 05 Pneumocgiiii caninii pneumonia ' in aigmptomatic HIV + pencond an pcnbonc with ARC. Jcfifincg Vicina, MD. The Bhoohlgn HoApital, Bnoahlgn, NV, USA. Pncumoc Aiii caninii pneumonia is the most common initial, Lifie-thdeatenlng opponiunibiic ingcction in pchaoni with AIDS. Montaliig (com the ginat epldode 06 PCP i4 a4 high a4 20—3oi. Sage and céficciivc phophylaxii would be woaihwhile to pncvcni the moabidiig and monialiig aobociatcd with PCP. 30 paticniA with T4 cell counts 250 wcac Aandamizcd to deceive Fancidan (1 tablet weekly) on placebo. Patient gnoupc wane companablc in tehmo 05 age, T4 counto, baielinc hematology and chemialnici. All wean (allowed cveng ihicc wcchi. Theme Want 4 cpiAadci 05 PCP duning the mean (allow-up pcdiod 06 7 months, all occunaing in the placebo gnoup. One 05 these wan (dial. In the placebo gnoup lab Aiudici wane liable except 504 incneacco in LDH and dccncaoei in Hgb and leukocyte countb in paiicnic developing PCP. In the Faniidan necipientd mild toxiciiicc included nausea (4/15) and mash (l/IS) not nequining discontinuation of dnug. Pnogacicivc anemia (2/15) and Acvccc lcuhopcnia [3/15) Acquiicd dosage modifiicaiion on discontinuation 06 the dung in 1 patient. In Aummaag, Faniidaa may paovidc cggcciivc pnophglaxio son ginii epiiodc PCP. Bone maanow Auppaebbion may be a Aignifiicani limitation to pnolongcd uic in Acme paticnib. The not 05 fialinic acid bupplcmcniaiion may help neducc this daug- induced monbidiig. 99 ~T2222 Phase I Tolerance Study of HPA-23 in Patients with AIDS and Preliminary Data of Anti-HIV Activity MFA-23 COOPERATIVE STUDY GROUP. (BRUCE L. MOSKOVITZ, Rhone—Poulenc, Inc., Monmouth Junction, N.J.) The heteropolyanion EPA—23 is active against HIV in vitro and was selected for study as a potentially effective antiviral compound for patients with AIDS. Sixteen, 16, 23 and 14 patients with AIDS received, respectively, 0.25, 0.5, 1.0 or 2.0 mg/kg daily doses of EPA—23, intravenously-administered, five days weekly (Monday-Friday) for up to eight weeks to assess the tolerance of HPA-23. Clinical changes and anti-HIV activity were monitored periodically. Forty—three of the 69 patients completed the entire eight-week course. Thirteen discontinued because of a concurrent illness, six discontinued because of a clinical adverse event, and seven discontinued because of laboratory test abnormalities (thrombocytopenia—b, 4+ proteinuria—l). HPA-23 produced a dose-dependent decrease in platelet count and increase in SGOT values. Other adverse events included leukopenia, granulocytopenia, fever, diarrhea and nausea. Over the eight-week course of treatment, no improvement in immunological function, measured by total lymphocyte count, T4 cell count, and T4/T8 ratio, was observed. No changes in clinical symptoms, development of new opportunistic infections, or occurrence of Kaposi's sarcoma lesions were apparent. Qualitative results of reverse transcriptase activity assays suggested a dose—dependent anti—HIV effect. We conclude that the toxicity of HPA-23 is predictable and acceptable. Longer-term studies to assess drug concentration-effect relationships, in vivo antiviral activity, and clinical efficacy of HPA-23 are warranted. _____“_ TP223 Open Study of AL-7Zl in HIV-Infected subjects with Generalized ' Lynphadenopathy Syndrome (LAS). MICHAEL H. GRIECO, M. LANCE, E.B. KLEIN, A. ENGLARD, G.F. MCKINLEY, K. ONG, et a1., St. Luke's/Roosevelt Hospital Center, New York, N.Y. Eight subjects with LAS associated with HIV infection consented to an open 8—week trial to evaluate the antiviral and innmnologic effects of AL—72l. CD4/CD8 ratios were less than 0.7 and CD4 counts below 550 an“. The drug was administered in 10 gm frozen sachets and reconstituted twice daily in 10 ml chilled orange juice before a fat-free breakfast and after a low fat dinner. Surveillance studies were conducted of clinical state, serum lipids, lymphocyte subsets, lymphoproliferative responses, and reverse transcriptase assay (RTA) following cocultivation of peripheral blood mononuclear cells. There were no significant drug-related clinical events during the 8 weeks of drug and the 8 weeks follow-up period. Seven patients remained clinically stable throughout the study and follow—up period. One patient, however, who always had less than 35 CD4+ cells, developed disseminated CMW after 4 weeks off drug and cerebral toxoplasmosls after 10 weeks off drug. Serial RTA were performed in 7 with detectable RT at baseline having an initial mean level of 73,419 cpm decreasing to a mean 44,653 at 6 weeks and 27,419 at 8 weeks. These changes in mean values resulted from decreasing levels in 5 of the 7 subjects. Pokeweed mitogen responses increased in 5 of 8 so that the baseline mean of 16,000 cpm rose to 30,300 at 4 weeks and at 28,923 at 8 weeks and then subsequently decreased to 18,223 at 4 weeks following treatment. No significant effects on serum lipids or T lymphocyte subsets were noted. The results of this study suggest that AL—721 may exert an anti—HIV effect and augment innmne responses in subjects with LAs. T2224 Combination Chemotherapy and Interferon in Kaposi's Sarcoma (KS) and AIDS. F.A. SHEPHERD, M.B. Garvey, W.K. Evans, M.M. Fanning, M. Kline, and S.E. Read. University of Toronto, Toronto, Canada. Thirteen males, median age 37 years (range 28-46), with extensive KS and AIDS were treated with combination chemotherapy and Interferon. There were four patients with stage III and 9 with stage IV disease (one pU1monary and 8 6.1. involvement). Treatment consisted of monthly courses of actinomycin-D, 1 mg/m2 and vinblastine, 6 mg/m‘, day l; bleomycin, 10 mg/m2, day l and 8; and human lymphoblastoid Interferon, 10 million units/m1 i.m. 3 times per week x 6 doses starting day 14. Forty-one treatment cycles were administered (median 3, range 1-12). Complete response was seen in one patient (24 weeks), and partial response in 4 patients (14-44 weeks). One patient had mixed response with re- gression of extensive skin involvement, but progression of pulmonary disease. Median survival of the group was 48 weeks (4-143+ weeks). Eleven patients died of progressive KS, one with lymphoma, and one with Pneumocystis pneumonia. Nausea and vomiting was mild to moderate and easily controlled. All patients had slight temperature elevation and muscle aches while receiving Interferon, both easily controlled with antipyretics. The median granulocyte and platelet nadirs at day 14 prior to starting Interferon were 600 x 109/L and 134,000 x 109/L, respectively and did not fall further while on Interferon. Four patients required hospital admission for neutropenia associated fever. Compar- ison of pre- and post-treatment T-cell subsets, 2'5'A synthetase levels, and mitogen responses demonstrated no improvement while on Interferon. Although a significant number of patients achieved response with this com- bined modality therapy, we feel that the duration of response, survival, and toxicity suggest that this form of therapy is not appropriate for patients with KS associated with AIDS. SUpported by Pacific Isotopes and Pharmaceuticals Ltd. Vancouver, Canada. TUE DAY, JUNEZ TP225 Effect of AZT Therapy on Quantitative Serum HIV Antigen. JQEL SPEAB‘, H. KESSLER‘, J. PO'ITAGE‘, C. BENSON', D. PAUL”, L. FALK”, et al. Rush~Presbyterian-St. Luke‘s Medical Center‘, Chicago. IL. USA, and Abbott Laboratories", North Chicago, IL, U.S.A. To determine the effect of AZT therapy on quantitative serum HIV antigen (Ag), we serially studied 18 HIV culture positive AIDS patients treated with AZT in accordance with the EW- AZT protocol. HIV Ag was determined prior to therapy and weekly thereafter using a commerically available enzyme immunoassay (Abbott Laboratories) which detects the p24 gag gene product. T—cell subset analysis was determined monthly. Ten of 18 patients were HIV Ag positive prior to the initiation of therapy. There was no significant difference i mean T— helper cell counts (67 vs 109/mm ) or T-suppressor cell counts (412 vs 1012/mm ) between HIV Ag positive and negative patients, respectively. In 9 HIV Ag positive patients with a mean pre-therapy quantitative Ag of 253 pg/ml (range: 23-804), the Ag decreased by a mean of 223 pg/ml (92% reduction) with a range of 56-731 pg/ml (range: SIS-100% reduction) after one week of AZT (1200 mg/day). In one patient HIV antigen decreased by 1961 pg/ml (80% reduction) after 4 weeks of AZT (1200 mg/day). Dose reduction of AZT (600 mg/day) in 2 patients was followed by slight increases in HIV Ag. AZT had to be discontinued in 7 patients after 12—46 days (intercurrent opportunistic infection, 3; toxicity, 3; progressive deterioration, 1), HIV Ag increased by a mean of 721 pg/ml (range: 30-2927) within a mean of 6.6 d (range: 2 to 11) of discontinuing AZT. Four of 8 patients who were HIV Ag negative at initiation of therapy became transiently HIV Ag positive within 3 weeks of beginning AZT. Initiation of AZT therapy in HIV Ag positive patients with AIDS is followed by a rapid decline in HIV Ag which rapidly returns to pre-therapy levels after AZT is stopped. This suggests that serial quantitatiou of HIV Ag may be a useful parameter by which to monitor AZT therapy. The clinical significance of this is as yet undetermined. Tflflfi PmHmeDfiaHma%fielfiMyfl0MlWmfifinmmfln Children with AIDS-related Complex (ARC). EDWARD CONNOR, S. MORRISON, A. MINNEFOR, J. KERESZTES, T. DENNY, J. OLESKE ET AL. C i ran 5 Hospital of NJ & UMD-NJ Medical School, Newark, New Jersey. We are presently conducting a Phase I study to determine safety, tolerance, and pharmacokinetics of single and multiple doses of oral RIB (I-beta-D-ribo- furanosyl-1,2,4-triazole-3—carboxamide) is stable children with ARC. This is an open study with sequential dose escalation. Patients were excluded if they had severe or progressive end organ disease. Five patients were enrolled in the first group (3 female, 2 male); mean age 26.2mo (16-61mo). Six mg/kg RIB was dissolved in 3ml water and given po after 6-8hr fast. Safety parameters included: vital signs, physical exam, stool guiac, CXR, EKG, CBC, platelet ct., reticulocyte ct., SMA-18, urinalysis, PT/PTT. Patients readily took the drug and all tolerated it well. All parameters remained stable except HGB which dev creased, mean 0.7Bgm (0.1-1.59m). This was greatest for the smallest children, could be accounted for by blood drawing and was associated with appropriate in- crease in reticulocyte ct. One patient developed mild eosinophilia. Following a single 6mg/kg dose mean peak plasma RIB concentration was 2.5uM (1.02-3.96uM) and occurred 1-2hr post dose. During multiple dosing the range of trough conc. at steady state was 2.05-2.8uM at 30 days and 1.85-2.9uM at 60 days. During the two months of this study parents reported decreased night sweats, increased activity and improved appetite. In addition, lymphocyte phenotyping was performed at baseline and after 30 and 60 days of daily RIB administration. There was a general trend toward increase of absolute number and percentage of T-helper cells with improvement in helperzsuppressor cell ratios. We are now proceeding with dose escalation. "’22-, A phase II Study of Betaser Interferon Given ' Patients With AIDS Related Kaposi's Sarcoma. STEVEN A. MILES, E CORTES*, SG MARCUS**, J CARDEN*, R RUDD*, and RT HITSUYASU*. *UCLA School of Medicine, Los Angeles, California and **Triton Biosciences, Alameda, California, USA. Betaser Interferon has shown antiproliferative activity in several neoplasms and has lg vitro antiviral activity against the human immuno— deficiency virus (HIV). To date we have treated l5 patients with AIDS related Kaposi's Sarcoma subcutaneously with 90 x 10 [U ad x 5 each wk. for 12 wks. Two patients had prior pneumocystis carinii pneumonia. Five had received prior chemotherapy, and 12 had positive culture for HIV prior to starting treatment and are evaluable for antiviral activity. Fourteen patients were stage II and one was stage IV. of 15 evaluable patients, 3 had partial responses, 5 have stable disease and 6 had progressive disease. One patient had an opportunistic infection (H. Tuberculosis) diagnosed while on study. To date, 2 of 4 patients who have had sequential HIV cultureshave become culture negative. Toxicity has been mild with no grade 2 toxicity seen in any patients. Side effects have been limited to fever, chills, malaise and local skin reactions at the site of injection. Preliminary results of T—cell subsets are presented below. Time on Study (months) Subcutaneously to 1 (n=13) 2 (n=10) 3 (n=4) 4 (n=2) Leu 3 pre Rx l0481628 11511680 9911274 9571378 post Rx 7471500 9051611 12081830 13011535 Leu 2 pre Rx 2201203 2731201 3841137 236169 post Rx 1561150 1481167 3481173 202144 Beta er Interferon appears to be a well tolerated treatment with i_n vivo activity against AIDS related Kaposi's Sarcoma. 100 TP228 Clinical and Immunological Response to IMREG with ARC/AIDS Patients. S, LANDESMAN*, ADRIEN MARCEL’, M. MURALI‘, H. DREW*, M. GOTTLIEB“, A. GOTTLIEB“. SUNY Health Science Center at Brooklyn'. Brooklyn, N.Y., IHREG Inc.*‘, New Orleans, La. sixteen patients with HIV disease (12 with AIDS related complex (ARC) and 4 with AIDS) received 6 biweekly intradermal injection of IMREG-I in a phase II clinical trial. IHREG-I is an inn-rune modulator comprised of a small molecular weight peptide prepared by a series of dialysis and HPLC separations from human leukocytes. At: entry the average T4 cell numbers for ARC and AIDS subjects were 309(62-761) and 51(0-71) respectively. Seven ARC and four AIDS subjects were anergic to PPD, tetanus toxoid and candida. Three ARC patients had minimal skin test: reactivity (<5mm induration) to tetanus toxoid alone. Nine of the 10 anergic ARC and 2 AIDS subjects regained full skin test reactivity to tetanus toxoid (8-30mm induration). While there was no change in absolute numbers of T4 cells in these subjects, the response to 1.0 ug/ml of Pl-IA (studied sequentially in 9 subjects) increased 2 to 4 fold in 7 patients and was unaltered in two. Associated with therapy was the resolution of constitutional symptoms such as fever and night sweats in 9 patients. There was no loss of body weight in any patient. The hematocrit and platelet counts were stable. No toxicity was noted with use of IMREG-I. These data suggest that: IMREG-I has some reconstitutive effect: on the cell mediated immune response in these patients as judged by skin test: reactivity and pHA responsiveness. No conclusion as to the long term efficacy of IMREG—I can be made based on this limited trial. Further studies are in progress. T2229 LONG TERM FOLLOW-UPOFBZPATIENTS TREATED BY RECOMBINANT ALFA 2 INTERFERON IN AIDS RELATED KAPOSI'S.SARCOMA. WILLY ROZENBAUM, S. GHARAKHANIAN, B. DUFLO, M. STENBERG, C. LINI. PITIE-SALPETRIERE HOSPITAL. PARIS FRANCE Over a Li years period, 82 male’ patients (homosexual or bisexual) witha mean age of 38.7 years (range 211-55) with AIDS-related Kaposi's Sarcoma (KS) were treated (83 courses) with recombinant leucocyte interferon alfa 2A (1‘ IFN alfa 2A). Two types of dosage regimen were used : 36 million unites (n=16) and I8 mu (n=67). A3 patients had cutaneous and/or lymph node KS, 30 had cutaneous and/or mu- cosal KS, 10 cutaneous and/or- visceral KS. 24 patients (29%) had a complete response (CR) with a mean duration of 10.6 months (range :1-36 months). 6 of them relapsed within 12.5 months (1' ‘1-28 months) after discontinuation of treatment, 2 responded completely with a new course of IFN. 9 patients had a partial response, 5 of them relapsed. None of the patients died in these groups. The CR rate was higher in the group of patients who had only cutaneous and/or lymph node KS (37%) in comparison with the group who also had mucosal (23%) or visceral lesions (10%). None of the patients with prior or concomitant opportunistic infection had a CR, neither did patients who had a positive CMV blood culture. Other factors which seem to be of relevance for the responding groups are: lymphocyte count, absolute number of auxillary (C011) cells, CDQ/CDB ratio, response to recall antigens, serum BZ-microglobuline level, serum IgA. 1* IFN alfa 2A is efficient in controlling AIDS-related KS, its' effect on life expectancy should be eva— luated. BRUCKER, M. GENTI- TR230 Treatment with high doses of immunoglobulins in HIV—relg ted thrombocytopenia. ADRIANO LAZZARIN‘, L. VOLTOLIN*, C. NEGRI*, P. CROCCHIOLO‘, M. GALLI*, S. CENZUALES**, *Milan University Clinic of Infectious Diseases; **Blood Transfusion Centre — "L. Sacco” Hospital, Milan, Italy. In our Clinic a severe idiopathyc thrombocytopenia (<15.000 PLT x mm ) was observed during the early phases of HIV infection in 21 out of 451 patients affected with LAS. These patients were in the most part asymptomatic. We treated with human immunoglobulins (0.4 g/kg daily for 5 days — Venoglobulines Mérieux) 10 thrombocy topenic patients (7 males, 3 females; age 20 to 27) presenting with hemorrhagic symptoms (3 purpuras, 3 metrorrhagias, 2 epista- xis and 2 hematomas due to microtraumas). A rise of platelets count was recorded since the third day of treatment; by the fifth day nine patientsiwere showing a four-fold increase of their pla— telets (FLT x mm 55000 1 9000). Platelets, however, returned to initial values 3 to 4 weeks after therapy was discontinued. In all but one patient (a woman with metrorrhagia) clinical symptoms sub sided. In conclusion, i.v. infusion of immunoglobulins at high doses in HIV—positive patients with thrombocytopenia seems to re— present a rather effective therapeutic approach; in our View, how ever, it should be considered in symptomatic patients only. TUESDAY, JUNE 2 TR231 Pharmacokinetics of Oral Azidothymidine (AZT) in 5 AIDS Patients. BAEQARA J, CHINNOCK, C. FLETCHER, F. RHAME, B. CHACE, C. SULLIVAN, H.H. BALFOUR, JR., University of Minnesota, Minneapolis, MN. Limited pharmacokinetic data are available on AZT. We studied 5 AIDS patients (4 male, 1 female; age range 19-32 years) receiving AZT after recovery from an initial bout of Pnegflocystis carinii pneumonia. 200 mg AZT was administered P0 every 4 h. Patients had sera drawn for pharmacokinetic analysis on the first dose according to the following sampling scheme: pre- treatment, 10, 20, 30, 45, 60, 90, 120, 180, 240 mins. Fifty sera were analyzed for AZT by HPLC. AZT serum conc. (Cp)-time data were subjected to model independent pharmacokinetic analysis. Mean pharmacokinetic parameters (n — 4) were: AUC, 4.09 1 1.29 pH hr; T 1/2, 0.6 i 0.25 hr; TBC/F, 3260 1 896 ml/min. The average Cp max was 3.54 ”M, which occurred 0.75 - 1.5 h post AZT dose. Cp min at 4 h. was < 0.5 uM in 4/5 patients. One patient was treated separately. His AUC (10.18 uM hr) and TBC/F (1230 ml/min) were substantially different (by a factor of >2) than the other 4 patients. This could not be explained on the basis of renal or hepatic dysfunction and may be a result of concurrent drug therapy affecting AZT metabolism. Further investigations are in progress. The previously estimated minimum level for in vitro antiviral effect with AZT is 1 pH. In our 5 AIDS patients receiving 200 mg PO q 4 h, AZT Cp were only above 1 pH for 1-1 1/2 h out of each 4 h dosing interval. This may not be sufficient to control viral replication in all patients and, if dosage is reduced due to toxicity we predict Cp will almost always be below 1 uM. TE232 The Efficacy of Azidothymidine in the Treatment of Patients with AIDS and AIDS-related complex: a double-blind placebo-controlled trisL TEE AZT COLLABORATIVE "ORKING GROUP. To determine the efficacy of Aridothymidine, AZT, a double-blind placebo- controlled trial of oral AZT we; conducted in 282 patients with AIDS and AIDS- related complex at 12 medical centers. Patients were prestrstified according to CD4 cell numbers and randomly assigned to receive a capsule containing either 250 mg of AZT or placebo every 4 hours for a total of 24 weeks. The study trial was terminated prematurely in September, 1986. One-hundred forty- five patients received AZT, and 137 patients received placebo. Twenty-seven patients had completed 24 weeks of the study; the remainder had completed at least 8 weeks. Nineteen placebo recipients and 1 AZT recipient died during the study (p<0.001). This increased likelihood of survival was comparable for patients with AIDS and AIDS-related complex who received AZT. Forty-five patients receiving placebo developed opportunistic infections compared to 24 receiving AZT (p<0.001). 81x AZT recipients and 10 placebo recipients developed Kaposik sarcoma (p>QZOL A statistically significant increase in the number of CD4 cells was noted in patients receiving AZT compared to those receiving placebo (p<0.001). After 12 weeks, the number of CD4 cells among AZT recipients with AIDS returned to pretreatment values. Similar trends in CD4 cell numbers were also noted among AZT recipients with AIDS-related complex but were less prominent. Twenty-nine percent of patients receiving AZT developed cutaneous hypersensitivity reactions compared with 91 receiving placebo (p<0.001). AZT appeared to prolong and improve the quality of life in a select group of patients with AIDS and AIDS-related complex over a 24 week period. 18233 Anti-HIV Seroconversion in Haemophiliacs Receiving Heat-Treated Concentrates. E.J. MILLER, P.A. LILLEY, D.S. THOMPSON, P.D. GRIFFITHS, P.B.A. KERNDFF. Departments of Haematology and Virology, Royal Free Hospital, London, and Luton and Dunstable Hospital, UK. In the UK, about two thirds of factor VIII used is imported commercially from the USA. The remainder, and all factor IX, is derived from domestic (NHS) volunteer plasma. In December 1984, when heated concentrates were first introduced, 78% of patients attending the RFH Haemophilia Centre who had been exposed to US commercial factor VIII in the preceding six years were anti-HIV seropositive. All 52 patients who had only received NHS concentrates were seronegative. At that time at least, therefore, HIV contamination appeared much less likely in domestic products. 82 patients seronegative at the time of their first exposure to heated products have been followed to December 1986. Of the 30 who received factor IX concentrate, all remain seronegative (total 35 exposure years). Of the 52 who received VIII concentrate (31 'wet heated' commercial, 18 'dry heated' NHS, 3 'dry heated' commercial) 49 remain sero- negative (64 exposure years). 2 patients receiving ‘wet heated‘ commercial VIII seroconverted within 4 months of starting treatment with heated product. However, both had received incriminated lots of unheated NHS VIII before changing to heated factor VIII. A third patient, treated with ‘dry heated' commercial VIII derived from non-anti-HIV screened donors, seroconverted 8-10 months after starting heated product. Although this patient had also previously received an incriminated lot of unheated NHS concentrate, HIV transmission by the'dry heated' commercial concentrates seems more likely. 101 T2234 The Infectivity of Anti—HIV Positive Blood Components STEVEN KLEINMAN*, THE TRANSFUSION SAFETY STUDY GROUP**, *American Red Cross, Los Angeles, CA, **other participating institutions. To determine transmissibility of HIV by transfusion, the Trans— fusion safety Study retrospectively tested donor sera collectedin late 1984 and early 1985 in five areas with high AIDS prevalence. The rate of anti—HIV positivity among 91 recipients of blood com— ponents from anti—HIV(+) donors (by EIA, IB, and RIP) was 89% 12-18 month post-transfusion. The 10 anti—HIV(—) recipients did not differ from the anti—HIV(+) by age or underlying disease. By blood component type, positivity rates were 91% (51/56) for RBC, 100% (lo/10) for platelets, 83% (5/6) for WB, 100% (2/2) for leu- kocyte poor blood, 85% (11/13) for FFP, and 100% (2/2) for cryo— precipitate. One anti—HIV(-) recipient and one anti-HIV(+) reci— pient received components from the same donation. Two of two re— cipients of washed RBC were anti-HIV(-); recipients of previous donations by the same donors were anti—HIV(+), indicating the potential infectivity of these donors. A third anti-HIV(—) reci— pient received only a few ml of RBC. Two other anti-HIV(—) reci— pients received components (FFP and RBC) from the same donor, sug- gesting that this donor was not infectious. These findings have important implications for assessing the importance of anti-HIV screening, the risks to recipients of components from anti—HIV(+) donors, and for establishing lookback policies. (Supported by Contracts No. N01—HB-4-7002 and NOl-HB-4-7003 of the National Heart, Lung, and Blood Institute.) “"3235 Improved Anti-HIV Screening Assay Using Recombinant Antigen Based Conjugate LARRV MIMMS, B. BRAUN, S. WUROBEC, L. PAUL, S. EARLE and L. VALDIVIA, Hepatltls7AIDS R&D, Abbott Laboratories, Abbott Park, Illinois 60064 Two major antigenic proteins of HIV, ENV and CORE, have been cloned and expressed 1n E. coli by recombinant DNA (rDNA) methodology and purified Wimwmflmfiydmmmwww.muewHHMammmsmmcmmd onto polystyrene beads which are used to capture anti—HIV from the specimen. Anti—HIV bound to the beads was detected in the assay using a probe solution containing rDNA HIV antigens coupled to horseradish peroxidase (HRPO). Unlike currently licensed anti-HIV tests. this assay requires no sample dilution and ls capable of detecting IgG, IgM and IgA. This recombinant antigen based screening assay is 8 to 64 fold more sensitive than current anti-HIV tests and shows significantly improved specificity. When 125 sera reactive by the current anti-HIV test but negative by Western Blot were tested, all were negative in this assay. 68 AIDS sera and 250 sera testing positive by current EIA and Western Blot were reactlve in this assay. Serial bleed studies indicate that the rDNA based screening assay can detect anti-HIV seroconverslons significantly sooner than current tests. As configured, this assay does not allow differentiation between anti-CORE and anti-ENV reactivity. rDNA CORE and ENV may be separately coated onto beads and coupled to HRPO to make tests which will discriminate anti-CORE and anti-ENV positivity. TP236 Prognostic Importance of Western Blot HIV Antibody Patterns in HIV ' Antibody Positive Hemophiliacs MARGARET V. RAGNI*, T.A. O'BRIEN**, J.A.SPERO*, J.H. LENIS* *Department of Medicine, University of Pittsburgh School of Medicine, Central Blood Bank of Pittsburgh, Pittsburgh, PA, and **DuPont Co., Wilmington, DE. Antibodies to specific HIV viral antigens were measured by a Western blot system using biotin-avidin detection (Biotech Research Labs, Rockville MD) on 36 HIV antibody positive hemophiliacs (HTLV-III ELISA, DuPont) on whom serial samples were available between 1977 and 1986, representing 2 to 8 years following seroconversion. Of these, 20 were Class IV (9 AIDS. 7 ARC, 4 other) and 16 were asymptomatic. At seroconversion, antibody to p24 (gag) appeared first. followed by antibody to gp4l (env); antibody to p55 (gag) was weak or absent at seroconversion in 26. developing one to three years after serotonversion in six of 26 or not at all in three of 26. Thirteen of 20 Class IV (8/9 AIDS, 2/7 ARC, 3/4 other) hemophiliacs lost (or never developed) antibody to one or more HIV gag (p15, 24, 55) or pol (p 1, 53, 64) antigens, as compared with one of 16 asymptomatic hemophiliacs (X - 12.81, p (.001). The development of AIDS was preceded (one to four years) by the loss/lack of antibody to p15 (in 5 AIDS patients), p53 (in 4), p24 (in 3), p55 (in 3), p64 (in 3), and p31 (in 2), each p (.05 as compared with non-AIDS patients. Absence of antibody to more than one (2-5) HIV antigens occurred in five of eight AIDS patients. The single AIDS patient with no loss/lack of antibody was the only one with lymphoma and no opportunistic infection. In conclusion, the loss or lack of antibodies to gag (p15, 24, 55) or pol (p31, 53, 64) HIV gene products appears to be associated with and occurs within one to four years before the development of AIDS in HIV antibody positive hemophiliacs. TUESDAY, JUNE 2 TP237 Frequency of Recent Blood Donation in HIV Infected Soldiers . JOHN G. MCNEIL*, J. WHAUN**, P. RENZULLO*, J. BUNIN*, J. BRUNDAGE*, *Division of Preventive Medicine, ** Department of Virus Diseases, Walter Reed Army Institute of Research, Washington, D.C. In October 1985, the Department of Defense mandated screening all active duty soldiers for the presence of antibody to human immunodeficiency virus (HIV). Data assessing frequency of recent blood donation by HIV infected soldiers and rate of infection in product recipients has important disease control implications. One hundred seventy—four HIV infected soldiers from a broad geographic dis- tribution were ascertained through general (not blood bank) screening. Each soldier was evaluated for a history of blood donation between March 1983 and April 1985. Twenty—six percent (45/174) reported donating at least once during that period; a rate almost ten times higher during this interval than reported for persons subsequently diagnosed with ARC and AIDS. A centralized effort to "look back" at living recipients of components donated by HIV-Ab positive soldiers ascertained through blood bank screening is in operation. Seven living recipients have been evaluated; 5 (712) are HIV-Ab positive by western blot. Two recipients were infected as long as 22 months before deter- mination of positivity in an asymptomatic donor. Although 70% of HIV infec— tions in the Army are determined by methods other than blood donor screening. "look back" does not currently include prior donations from soldiers deter- mined HIV‘Ab positive by other than blood bank screening. These data describe a situation with far—reaching disease control conse- quences. Increased effort to evaluate and improve donor self-deferral and "look back" is essential. TE238 HIV Infection in the Edinburgh Haemophiliac Cohort CHRISTOPHER A. LUDLAM*, R.J.G. CUTHBERT”, D. BEATSON‘*’, F.A. LAINSON**, J.F. PEUTHERER", C.M. STEEL ’**. ”Dept. of Haematology, Royal Infirmary Edinburgh. “*Dept. of Bacteriology, University of Edinburgh. ””*MRC Clinical Population and Cytogenetics Unit, Western General Hospital, Edinburgh. We previously reported on a cohort of 33 haemophiliacs who were transfused in April 1984 with a single batch of factor VIII contaminated with HIV. In our initial study we found that 15 patients had developed anti—HIV antibodies, but we have since identified 3 later seroconverters. We now report a 4 year follow up of this cohort. Patients who became seropositive received significantly more bottles of the contaminated batch of factor VIII. All patients receiving more than 30 bottles became seropositive. The annual factor VIII consumption was significantly greater in the seropositive group. Thirteen patients developed HIV-specific antibodies within 15 weeks of exposure to the contaminated batch, whereas 4 patients developed antibodies more than 20 weeks after exposure, and one patient between 11 and 36 weeks after exposure. There were no differences in total dose of batch received, annual factor VIII consumption, pre—exposure T4/T8 ratios or absolute T4 counts between early and late seroconvert rs. Mean T4 counts in the seropositive group have declined from 0.73 x 10 /1 before exposure to 0.33 x 10 /l at the time of writing. Mean T4 counts in the sero— negative group have remained static at 0.77 x 10 /1. In the seropositive group one patient has AIDS, 3 have ARC, 3 have PGL and one has thrombocytopenia. Ten seropositive and all the seronegative patients remain asymptomatic. T2239 Transfusion—Associated Transmission of Human Immunodeficiency virus (HIV) from a Seronegative Donor - Coloraoo CATHY A. HAEVSKYt, B. DILLONi, A. SCOTTt, F. WOLF*, D. COHN#*, lColorado Department of Health, *tDenver Disease Control, Denver, Colorado, U.S.A. In November 1985, a male donor at a Colorado blood collection facility was seropositive for HIV antibody (ELISA and Western Blot) although previously donated units (August and April 1985) were ELISA negative. Recipients of the April 1985 donation were seronegative by ELISA when tested in May 1986. The 2 recipients of the August donation were subsequently found to be seropositive. Recipient $1, who had no other risk factors for HIV infection, received units from 15 different donors. Recipient #2, who had other risk factors for HIV infection, received units from 3 different donors. Another donor (seronegative April 1986) was common to both August recipients. of the remaining 14 donors, 12 resided in Colorado and were seronegative when retested 5 months or more after the August donations. Two donors outside Colorado have not been tested. Interviews of the seropositive donor and recipients suggest donor infection through sexual contact 12 weeks or less prior to his August donation when he may have been falsely negative on ELISA or virenic but without detectable antibody. Sexual contacts (18) of the seropositive donor and 2 recipients were identified. Of those in Colorado (11), all were located, 9 tested and 2 seropositive. Contacts outside Colorado (7) have not been notified. This is the first reported case of HIV transmission from a sero- negative blood donor since screening for HIV antibody in blood collection facilities. 102 TP240 Confidential Exclusion of Donated Blood: Evidence for Donor ' Compliance. l. PINDYCK, B. HOSEIN, A. WALDMAN, W. YING, M. LOWY, and C. BIANCO, The New York Blood Center, New York, N.Y. 10021. Recognition that AIDS was a disease transmissible by blood necessitated introduction of stringent measures to ensure safety of the blood supply. Early in 1983, The New York Blood Center introduced a questionnaire which allows individuals who appear medically acceptable as blood donors to review. before their donation, information about high risk of exposure to AIDS. They are then asked confidentially to designate their donations "for transfusion" or for "laboratory studies only". This system has been maintained in addition to the ELISA assays for antibodies to HIV, introduced in April of 1985, because the population of self-excluders may contain individuals who are exposed to HIV, but have not yet developed detectable antibodies. Analysis of results from 459,165 blood donations show that the 98.2% who designated their units "for transfusion“ had HIV antibody prevalence of 0.092, while the 1.82 who designated their units "for studies only" had a prevalence of 2.12. The prevalence of Hepatitis B surface antigen was 9 times higher among "for studies" donors than among "for transfusion" donors. These differences were highly significant (p<0.001) indicating that many donors are aware of their higher risk of exposure to HIV, find it difficult not to donate at a blood drive, and therefore designate their units "for studies only", in compliance with systems designed to improve the safety of the blood supply. T2241 MECHANISM OF B CELL DYSFUNCTION IN HAEMOPHILIA RAJAN MADHOK, JAGRACIE GDO LONE CD FORBES UNIVERSITY DEPT. OF MEDICINE GLASGOW ROYAL INF .SCOTLAND In a previous study we showed a significant increase in serum 196 levels in HIV positive haemophiliacs (INT.CONG.AIDS PARIS 1986) we have investigated the mechanism of this increase in both HIV positive (asymptomatic) and HIV negative haemophiliacs. In all positive patients the increase was polyclonal. Using the T cell dependant B cell mitogen PNM our results show significantly higher levels of SPOHtaneOUS IgG secretion in both positive and negative patients relative to normals. No further increase on PHM stimulation was seen. Using the T independent B cell mitogen Staph.Aureus Cowan strain 1, no significant change was seen in positive patients. The T 4 cnt in HIV positive pts. showed corre.coief. of .57 with spontaneous IgG secretion. HIV P05 HIV NEG CONTROL UNSTIM STIM UNSTIM STIM UNSTIM STIM PHM 320 290 115 128 97 110 STAPH 370 115 115 97 80 320 medians are shown Non parametric stats. The B cell dysfnc. in HIV positive haemophiliacs appears to be both due to T4 cell depletion and a intrinsic B cell defects. TP242 Detection of Human T-Cell Lymphotropic Virus-I (HTLV-I) Antibodies ' by an Enzyme Immunoassay (EIAi. A.J. BODNER‘, A.J. CORRIGAN*, 5.5. ALEXANDER*. T.S. CLEMENT*, T.A. O'BRIEN**, W.R. FREDERICK***, et 81., *Biotech Research Laboratories, Inc., Rockville, MD, **Du Pont, Wilmington, DE. *** Howard University Cancer Center, Washington, D.C. An EIA has been developed to screen blood components for antibodies to HTLV-I, the virus linked with Adult T-Cell Leukemia (ATL) and implicated in other diseases as well. The format of the HTLV-I test is identical to that of the Du Pont HTLV-III antibody screening test, allowing the two tests to be used simultaneously. Simultaneous testing for HTLV—I and III antibodies may become necessary if the risk of contracting HTLV-I infection from contaminated blood products is eventually judged unacceptably high. Simultaneous screening may also become common clinically if the prevalence of dual infection with HTLV-I and III increases, either through HTLV-III infection of previously HTLV-I infected individuals or through spread of HTLV-I by the same risk fac- tors as for HTLV—III. Preclinical evaluation of the HTLV-I EIA confirms that it is both sensitive and specific. 24 of 24 ATL patients were reactive, while only 4 of 1,752 (0.21) individuals at low risk for HTLV-I infection were re- active. HTLV-III antibodies are not reactive in the HTLV—I EIA. Sera from a group of intravenous drug abusers were screened with the HTLV-I and III EIAs and western blot (WE) tests. 10 individuals reactive on the HTLV-III W3 were nonreactive on the HTLV-I EIA but reactive on the HTLV-III EIA. 9 individuals reactive on the HTLV-I WE are reactive on the HTLV-I EIA but nonreactive on the HTLV—III EIA. Another 10 individuals reactive on both HTLV-I and III "B were reactive on both the HTLV-I and III EIAs. The HTLV-I EIA and a confirmatory WB test are currently being clinically evaluated at several blood research centers in the United States. TUESDAY, JUNE 2 TP243 SCREENING 0F VOLUNTARY BLOOD DONATIONS FOR ANTIBODIES TO HUMAN ' IMMUNODEFICIENCY VIRUS (anti-HIV) - EIGHTEEN MONTHS EXPERIENCE S. Mankikar, J.B. Derrick, B.K. Buchner, P. Humphreys, M.G. Davey, Canadian Red Cross Blood Services, National Headquarters, TORONTO, ONTARIO By November 1986 the Canadian Red Cross had screened 1.25 million blood donations for anti-HIV using the Abbott enzyme immunoassay (EIA). Blood found repeatedly reactive by EIA is discarded and the antibody status is confirmed by Western blot (H3). The data indicate that during the first six months of testing, initially BIA reactive, repeatedly EIA reactive and WE positive rates gradually decreased. During the subsequent seven months, however, there was a gradual increase in all three rates. It is not clear whether this is due to modifications in the test system or to changes in the donor population. Data was also analyzed in terms of geographic location, sex, age and frequency of donation. Prevalence of anti—HIV in urban donors was approximately four times greater in rural donors. Although the highest incidence of AIDS is reported in the Province of British Columbia, the highest anti—HIV prevalence was observed in the Province of Quebec. The highest anti—HIV prevalence was in male donors between 30-39 years of age. Nationally, the WB rate fluctuated from a high of 0.034% in November 1985, to a low of 0.008% in May 1986. The data indicate that in spite of the inherent problems with the W3 system it is still very important in establishing the donor antibody status. Data which will have been accumulated on the screening of over 1.82 million donations by the end of April 1987 will be analyzed for presentation of additional information. T2244 W hemophilia cohort in follow-up since 1983: Virologic, immunologic and clinical relationships. Wm E. BETH-GIRALDO*, R. DE BIASI", E. MIRAGLIA**. G. CASTELLO*, S. CEPARANO* et al., *Ist Naz Tumori, **Ctr Med Soc Hemophilia, Naples, Italy. Since longitudinal studies are needed to establish the effect of HIV infec- tion on the immune system, we have chosen to follow-up a cohort of patients with coagulation defects (>245 subjects). While 41.5% of 79 HIV-seropositive hemophiliacs have a LAS and 11.4% (9 patients) a lesser AIDS, 5.1% (4 patients have come down in 1986 with AIDS (3 AIDS/001, 1 AIDS/KS). Comparison of case/ control matched HIV-seropositive, symptomatic subjects with seronegative, asymptomatic ones revealed a significant reduction of T-helper to T-suppressor ratio (p<0.001) and absolute T-helper cell counts (p<0.001) as well as an in- crease of T-suppressor cells (p<0.01) in the seropositive group. Furthermore, a significant increase of urinary neopterin levels was observed in that group. Analysis of the antibody profile to herpesviruses showed elevated anti-EBV-VCA titers (IgG) with a 4-fold increase of geometric means in case/control matched seropositive subjects. Moreover, they have significantly more (p<0.005) IgM antibodies to EBV-VGA. There was no association however with antibodies to CMm HSV-l and HSV-Z. These findings strenghten the concept that LAS may be the result of an important interaction between EBV and HIV in hemophiliacs, since both viruses may be responsable for polyclonal B-cell activation. Furthermore, data will be presented on correlations between neutralizing antibodies to HIV, antibody detection by 11F and Western blot analysis com— pared to immunological profiles and clinical evolution of this AIDS risk group. TP245 UV-Laser Inactivation of Virus in Blood Products. ' o o *, J.C. FRATANTONI*, N.A. LOWEN*, P. ALBRECHT* and R.F. BONNER**, FDA* and NIH**, Bethesda, MD. Evaluation of UV radiation to selectively inactivate virus in blood products was conducted by uniform treatment of attenuated poliovirus, platelets and plasma with 40 nsec pulses of 308 nm (UVB) radiation emitted by a Xecl excimer laseE. Dose rates and doses of UVB were varied from 0.1 to 1.3 MW/cm per pulse and 0.51 to 53.7 J/cm , respectively. Virus and platelet samples were prepared in isotonic phosphate buffer containing 5% albumin. Biologic activities measured included: 1) cytopathic effect of the virus; 2) platelet aggregating activity; 3) spontaneous release of serotonin from platelets; and 4) plasma prothrombin time (PT) and partial thromboplastin time (PTT). Poliovirus showed a dose- depagdent titer decrease of 4 to 6 log 0 with UVB=10.8 to 21.5 J/cm . Although rate and amplitude of platelet aggregation decreased in a dose-dependent ganner over the range of UVB doses used, at UVB=10.8 to 21.5 J/cm aggsegation amplitude was decreased 20-30%. At UVB=10.8 J/cm serotonin release was 5% above control, while at the highest dose of UVB (53.7 J/cmz), 10% was released from irradiated platelets. Plasma proteins were minimally affected by UVB=10.8 J/cm : 10% above control, PTT 7.5% above control. with UVB=21.5 J/cm , PT and PTT of irradi- ated plasma were <20% above control. The observed inactivation of a hardy virus by doses of UVB which do not abolish the biological activity of platelets or plasma proteins suggests that UV-laser treatment is a potential method for diminishing the viral bioburden of blood products containing anucleate cells. 103 FOLLOW-UP OF WESTERN BLOT POSITIVE BLOOD DONORS-VICTORIA,AUSTRALIA. . *K.McGrath, *‘A.Mi'ch, **W.Maskell, **T.Howard, *J.Morris, **C.R.Lucas et a1. (**Fairfield Hospital, Melbourne Australia. *Victorian Blood Transfusion Service, Victoria Australia.) Nationwide blood donor screening was introduced in Australia on lst May 1985. In Victoria sera repeatedly reactive by Enzyme Immuno Assay (EIA) (Electro Nucleonics Inc.) were referred to the State Reference Laboratory for confirmatory testing by Western Blot (WE). Sera were regarded as positive if precipitin bands were detected at p24 and/or at p41 as recommended by C.D.C.[l of 214,699 donors screened in the first 12 months 924 (0.4%) were repeatedly reactive by EIA; 15 of these(0.0065s) were positive by WB (p24 in 5, p41 in 2, p21 plus p41 in 7). [] Fourteen were referred for clinical assessment (10F & 4M). Their ages ranged from 21 to 49 years. No donor admitted to risk factors for HIV infection; 10 were married (8F 5 2M) and one divorced (P). All were asymptomatic. One donor had generalised lymphadenopathy and physical examination was normal in the others. [1 Among spouses, tests for anti-HIV by EIA were negative in all 10 and by WB in the 7 tested. [] 0f 27 cultures for HIV from 14 donors only one, from the donor with lymphadenopathy, was positive. [1 The 14 WE positive donors have been reviewed on 3 to 8 occasions over 4 to 17 months. Each has remained well and lymphadenopathy has not been detected in the follow-up examinations of the donor in whom it had been initially present. [1 In subsequent serological testing 5 have become negative by EIA and 13 of 14 remain positive by WB (p24 in 7, p41 in 2, p24 plus p41 in 4). Our experience suggests that in this population the majority of donors reactive by WB test are not infected with HIV. This has resulted in modification of both WE interpretation criteria and blood donor notification policy in Victoria. T2247 Risk Factors for Antibody to HIV in New York Blood Donors: Validation of AIDS Risk Classification and of Confidential Donor Self-Exclusion at the Time of Donation CHARLES S- RABKIN*, N. VAN DEVANTER**, W. E. EWING***, and J. PINDYCK**, *CDC, Atlanta GA, **NY Blood Center, ***NYC Dept. of Health, New York NY. We studied blood donors in the New York metropolitan area, a region of high incidence of AIDS, to determine prevalence of antibody to HIV, risk factors for seropositivity, and potential sexual transmission. From April 1985 - May 1986, the Greater New York Blood Program collected 470,000 blood units, 8000 of which were confidentially donor-designated to be used for laboratory studies only. Anti-HIV by Western Blot was present in 337 (0.08%) units donated for transfusion and in 133 (1.6%) units donated for studies (relative risk = 20). Two hundred-fourteen seropositive donors from both groups have been interviewed, 169 men and 45 women. One hundred twenty-nine (90%) of 144 donors for transfusion and all 70 donors for studies had known risk factors for AIDS: male homo— or bisexuality (62%), intravenous (IV) drug use (4%), male homo— or bisexuality and IV drug use (61), blood transfusion (1.4%), and sexual contact to a member of an AIDS risk group (152). Fifteen seropositive donors, 12 men and 3 women, had no known AIDS risk factors. None of the 15 had received hepatitis B vaccine, acupuncture, or artificial insemination, and none was a health care worker; 2 had received immune globulin since 1975, and 5 reported prostitute contact 1 to 5 years before interview. Twenty—two sex partners of seropositive blood donors of opposite sex were also studied; anti-HIV was detected in 2 of 3 bisexuals, in 1 of 2 IV drug users, and in 1 transfusion recipient, but not in 16 heterosexual partners without other risk. Despite a high endemic incidence of AIDS in the New York area, anti-HIV is rare in blood donors, most seropositives are in known AIDS risk groups, and new risk factors are not apparent in seropositives not in risk groups- TP248 Analysis of discrepant anti—HIV ELISA reactives. D. THOMAS, I F.K. MUNDON, D. ZIMMERMAN, D. LARSON, L. GOWAN, and S. WILHELM, Electro—Nucleonics, Columbia, MD 21046. Conflicting results are sometimes obtained in tests for the presence of antibody to HIV in plasma and serum samples, depending on the particular kit being used in the screening test. We examined samples from thirty—three blood bank donors with histories of repeatedly reactive plasma. of 33 samples received, 19 were reported to be repeat positive when analyzed in a competitor's test at the blood bank. Comparative testing with reagents from two other manufacturers showed that inconsistencies were present within the ELISA data generated from the different kits. We have used 3 independent methods (Western blot, IFA, and competition with labelled anti—HIV human antiserum) to further analyze these plasma samples. For seven of the eight samples which demonstrated Western blot reactivity, the results indicated the presence of antibody only to a protein with M = 24,000. The eighth sample (sample 5) contained antibody to other HIV prgteins in addition to p24. Only 2 of the 33 samples appeared positive by IFA. These IFA results were confirmed independently by an outside laboratory. The IPA—negative samples could not compete with authentic anti-HIV human antisera for binding to plates that contained bound HIV protein. In this same competition assay, however, sample 5 showed complete inhibition of binding; sample 14 showed partial inhibi- tion. We conclude that the use of Western blot as a confirmatory test may be misleading in the case of "p24 only" reactivity, and all but 2 of the 19 samples originally designated as repeat reactives must be considered to be false positives. TUESDAY, JUNE 2 T2249 A105 STUDIES IN HENVAN HAEHDPHILIAcs Dr. G.N. Hiton i, H.R.C.Path., Prof. T. Bowry, M.R.C.Fath Prof. E.G. Kasili, M.D., M.R.C.Psth., University of Nairobi. Kenya. Fifty one consecutive black Kenyan patients with haemophilis A (ho), Christmas disease (5) and Van willebrand's disease (3) were tested for HTLV-III antibodies with an ELISA test. Positive results were confirmed by Western blot analysis. 12 of the AD patients (30%) with haemophilia A were seropositive. None of the patients with Christmas disease or Von Uillebrand'a disease were seropositive. Our results indicate a link between the use of commercial Factor VIII concentrates and aeropositivity. These studies also indicate that the rate of exposure of the Kenyan haemophiliacs to the HLV-III virus is not as high as reported elsewhere. This is probably related to limited use of factor con- centrates in Kenya due to the prohibitive cost of the concentrates. None of the 51 patients has clinical AIDS but h seropoaitive patients have extrsinguinal lymphadenopsthy. Although there are many studies on sexually transmitted AIDS in black Africa, there are very few reports on AIDS studies on haemo- philiaca. This paper represents one of the few reports on AIDS studies in black African haemophiliaca. Ongoing work includes T-cell subset studies and attempts to isolate the AIDS virus from the patient. T2250 HIV Infection: Surveillance of Heat Treated Factor VIII in the UK Criteria Based on Retrospective Studies of Unheated Factor J. CRASKE*, T. SNAPE**, C.R. RIZZA, ROSEMARY SPOONER“", ANDREW PEARSON****, Wehester, MBlood Products Laboratory, Elstree, Herts,***Haemophilia Centre, Churchill Hospital, Oxford and the UK Haemophilia AIDS Group, ****CDSC, PHIS, London. Criteria are given for defining a transmission event of HIV from heat treated factor VIII and IX concentrates to man. Retrospective information was obtained appertaining to the use of seven batches of unheated factor VIII and one batch of factor IX concentrate in patients from England. seven out of 22 (32%) patients seroconverted with the batch of factor VIII for which most information was available. The attack rate of HIV antibody negative haemophiliacs receiving this batch was seven out of 12 (58%) . There were 13 seroconversions amongst the 179 (7.3%) haemophiliacs who had received factor VIII concentrates from one of seven batches. One patient seroconverted of 24 (4%) who had received factor IX concentrate from one batch for which there was information. Three individuals had HIV antibody before exposure to this batch so the TRUE ATTACK RATE was 1 in 17 (6%) . The batches of unheated concentrate were used between 1981 and 1985. Testing of recipients started in the autumn of 1984. The total number of seroconversions was 1_4 out of 203 patients (7%) and the attack rate corrected for known prior exposure in 3Tindividuals was 14/167 (8%) . A strategy for the surveillance of heat treated factor is proposed. 104 Plenary Session IV vv-1-1 Public Health Measures for Prevention and Control of AIDS DONALD R. HOPKINS M.D., Centers for Disease Control, Atlanta, Georgia, USA Epidemiological surveillance, epidemiological research, and laboratory research are the basis for existing and potential interventions to help prevent and control the unprecedented threat posed by AIDS and HIV infection. Dissemination of information to the public, health education, individual counseling and testing of persons whose actions or circumstances put them at increased risk of infection, prevention and treatment of I.V. drug abuse, and serological screening of donated blood, sperm and organs are the main public health measures which are now available. The extent of application of these measures varies widely in different target U.S. populations. All require thorough evaluation. Asymptomatic infectious persons are the largest source of new infections; they need to know that they are infected, and be counseled as quickly as possible. Even partly successful drugs to delay onset of symptoms in infected persons would provide a significant new incentive for potentially infected persons to be tested voluntarily, but the scope of this pandemic will be decided before any vaccine or curative therapy is available for general use, if ever. Strong informed leadership is required at all levels to minimize irrelevant distractions and keep attention focused on the most important issues in this life and death struggle. W.1.2 ABSTRACT NOT AVAILABLE AT TIME OF PRINTING VV.1.3 Significant Contributions of Community Organizations PAULA VAN NESS, Former Chair of National AIDS Network; Centers for Disease Control, Atlanta, GA, USA. The AIDS crisis has presented multiple challenges to communities throughout the world. In the United States a network of community— based organizations, now spanning all 50 states, has developed over the past few years. In the absence of a vaccine and effective treatment for the infection, these community-based organizations have borne the brunt of developing and maintaining cost-effective social service programs and educational efforts to reduce transmission of the virus and to counter unwarranted fear in the general public. Working in conjunction with other public and private organizations on the community and national level, these organizations have also contributed significant leadership in identifying community needs and promoting other groups' involvement in providing information/education and vital human services to their constituencies. Specific examples of the significant accomplish- ments of these organizations will be discussed and analyzed. WEDNESDAY, JUNE 3 105 W.1.4 Research on HIV infection among intravenous drug users: State of the art and state of the epidemic. Don C. Des Jarlais, New York State Division of Subtance Abuse Services, New York, NY. As the largest group of heterosexuals infected with HIV in the United States and Europe. intravenous drug users will play a key role in the future of the AIDS epidemic in those regions. This presentation will review emerging critical issues in HIV infection among IV drug users. In epidemiology there is not yet a satisfactory explanation of the great geographic variation in seroprevalence rates nor a good understanding of the efficiency of heterosexual transmission to non-IV drug users. In natural history, HIV infection appears to lead to a variety of fatal outcomes in addition to surveillance definition AIDS; co-factors for infection outcomes need more intensive study. In prevention, basic AIDS education does lead to risk reduction, but methods of increasing risk reduction have not yet been fully assessed. Epidemiology—Heterosexual Transmission vv-2.1 Multicenter Study of HIV Antibody in U.S. Prostitutes W.W. BARRON, J.B. COHEN, J. FRENCH, P. GILL, R.K. SIKES, J. WITTE, et al., CDC Collaborating Group on HIV in Selected Women, Atlanta, GA, USA. To assess seroprevalence of antibody to human immunodeficiency virus (HIV) and risk factors for a positive anti-HIV test, we are studying women who have engaged in prostitution since 1978. Prostitution is defined as the exchange of oral, vaginal or anal sexual exposures for money or drugs. Serum is tested for HIV antibody by an enzyme immunoassay supported by Western blot assay, for hepatitis B seromarkers by radioimmunoassay, and for antibody to syphilis by RFR and MHA-TP, confirmed by FTA-ABS. As of January 28, 1987: Number positive/Number tested (percent) Research Site Anti-HIV Hepatitis B Syphilis Las Vegas 0/26 (0) 4/20 (20.0) 0/18 (0) Colorado Springs 1/67 (1.5) 12/54 (22.2) 0/52 (0) Atlanta 1/92 (1.1) 26/82 (31.7) 11/87 (12.6) L05 Angeles 7/136 (5.2) 78/109 (71.6) 38/119 (31.9) San Francisco 7/126 (5.6) 41/102 (40.2) 9/102 (8.8) Miami h0/210 (19.1) 93/169 (55.0) 81/179 (45.3) Newark-Jersey City—Paterson 9/13 (69.2) 12/12 (100.0) 2/13 (15.4) Women with antibody to HIV tended to have seromarkers for hepatitis B (odds ratio=4.6; CI=2.3-9.2) and antibody for syphilis (0R=2.1; CI=1.2-3.8). Measures of parenteral drug use, especially "shooting gallery" attendance (OR=4.0; CI=2.1-7.5), and unprotected sexual exposures with many "nonpaying" partners (r=.124) were associated with a positive anti-HIV test, even after effects of place were statistically controlled. About 80% reported using condoms, but only 8 women had used them with each vaginal exposure. All 8 were anti-HIV negative. Treatment for drug addiction and the proper, more frequent use of condoms should reduce risks of HIV infection in female prostitutes. VV.2.2 Human Immunodeficiency virus (HIV) among Female Prostitutes in South Florida. MARGARET A; FISCHL, GM DICKINSON, S FLANAGAN, MA FLETCHER. University of Miami, Miami, Florida. To evaluate the prevalence of HIV infection among sexually active heterosexuals, prostitutes in south Florida were evaluated. Prostitutes from an economically depressed inner city area and a middle class urban area were recruited. Ninety prostitutes from an inner city area were studied. All were between 17 and 28 years of age, from the lower socioeconomic group, had less than 12 years of education, and had arrest records. Sixty used intravenous drugs. Thirty-seven (#11) had anti-HIV antibody. 0f the 63 who used intravenous drugs, 29 (461) had antibody to HIV, and 8 (301) of the 27 who did not use intravenous drugs had antibody to HIV. Factors associated with HIV antibody (p<0.05) included a greater number of clients per week (28.7 t 5.2, seropositive group; 20 t 11.7 seronegativs group), number of black clients (A91 vs. 151), participation in vaginal intercourse (60% vs. 261), hepatitis 3 antibody (58% vs 23%), syphilis (681 vs. 301), number of pregnancies (3.8 t 2.0 vs.1.8 _ 1.3), and gynecologic surgery (871 vs. 37%); whereas, a negative sssocstion (p>0.05) occurred with length of prostitution, out of town clients, repeat clients, working outside the south Florida area, and fellatio. Twenty-five women from escort services were also studied. All were between 21 and 32 years of age, from the middle socioeconomic group, and were high school graduates. None had anti-HIV antibody. These data suggest that inner city prostitutes in south Florida have a high prevalence of HIV antibody and that the major risk factors for infection appear to be both intravenous drug use and multiple heterosexual partners from an area with a high incidence of AIDS WEDNESDAY, JUNE 3 w_2.3 AIDS and HIV Infection, Belle Glade, Florida. KENNETH G. CASTRO*, S.LIEB**, C. CALISHER*, J.HITTE**, H.W. JAFFE*, THE FIELD STUDY GROUP, *Centers for Disease Control, Atlanta, GA, & Fort Collins, CO, **Florida Department of Health & Rehabilitative Services, Tallahassee, FL, USA We studied the occurrence of AIDS and HIV infection in Belle Glade, Florida, because of the high cumulative incidence rate of AIDS (375/100,000) and high proportion (8/62; 13%) of AIDS patients with no identified risks. Most of the AIDS patients resided in an area characterized by high rates of intravenous (IV) drug abuse and sexually transmitted diseases. Nineteen (32%) of 59 adults with AIDS could be directly linked to at least one other reported AIDS case by sexual contact, sharing of needles during IV drug abuse, or both. From February through September 1980, we conducted a community-based seroepidemiologic study to identify risk factors for HIV infection. Twenty-nine (3%) of 844 adults tested had antibody to HIV, including 17 (AZ) of 441 men and 12 (3%) of “03 women. The highest age-specific rate (62) was among persons aged 18-29; no person over age 60 was seropositive. None of 144 children aged 2-10 years had antibody to HIV. No clustering of infected persons within households occurred, except for infection in sex partners. Compared with adults who were seronegative for HIV antibody, adults with HIV antibody were more likely to have antibodies to hepatitis B virus (56% vs. 25%, p<0.001) and to Treponema pallidum (58% vs. 22%, 0R= 5.0, p<0.001). The presence of antibodies to five arboviruses prevalent in south Florida or the Caribbean was not significantly correlated with HIV infection. In Belle Glade, the high cumulative rate of AIDS appears to be the result of HIV infection in IV drug abusers and their sexual partners; transmission through mosquito vectors is unlikely. Vv_2_4 Case control study of HIV—seropositive versus HIV—seronegative European expatriates in Africa LUC EONNEUX, H TAELMAN, CORNET**, G VAN DER GROEN, P PIOT. Institute of Tropical MEdicine, Antwerp; Ministry of Foreign Affairs, Brussels. Of 3805 European expatriates screened at the Medical Center, Ministry of Foreign Affairs, Brussels or the Hospital for Tropical Diseases, in Antwerp, 27 (0.7 Z) were HIV—antibody positive in 1985, and of 4398 European expatria— tes tested in 1980, 46 (1 Z) were HIV seropositive, including the 27 of 1985 (38 M and 8 F). A standardised questionaire was offered to 30 seropositives (24 M and 6 F) between June and December 1986, asking for residence, sex— life and other risk—factors. 49 (39 M and 10 F) sero—negative European ex- patriates were recruited as controls at teh same centers in November and December 1986, and matched for age, sex and residence. European male sero— positive expatriates had significantly more sex—partners (p< 0.0001), more contact with prostitutes (p < 0.001), and more injections (p550 0/5 anal intercourse, or sex dur1ng menstrual periods were not necessary for HIV infection. Thus, HIV transmission can occur after years of routine vaginal intercourse especially once the male has severe imrrune deficiency. These findings suggest that rapid replication of HIV and death of T4 cells may be linked in vlvo, with low T4 counts heralding a high risk of both AIDS and sexual infectivity. If true, effective antiviral drugs may reduce not only AIDS but also incident HIV infections. Virology—Vaccines Vv 3 1 Expression of HIV Genes by Recombinant Vaccinia Viruses ' ' . Earl, T. Fuerst, C. Flexner, F. Falkner— -Gunter, S. Chakrabarti and B. Moss. Nat. Inst. of Allergy and Infectious Diseases, Bethesda, MD. Recombinant vaccinia viruses that express HIV env, gag, pol and tat genes were made. When the entire open-reading-frame for the env gene was expressed, gp160 was synthesized, cleaved to form gp120 and gp41, and transported to the cell surface. Both gp160 and gp41 were exclusively cell associated whereas approximately half of the gp120 was in the medium. Exclusive synthesis of gp120 was obtained by introducing a stop codon before the cleavage site. The majority of gp120 made under these conditions was extracellular and the electrophoretic mobility of the protein was similar to that of the cleaved product of gp160 indicating that the transmembrane and anchor sequences were not necessary for glycosylation or transport. Enhanced expression of the entire gp160 gene and the truncated gp120 form were obtained with a newly developed hybrid vaccinia virus/bacteriophage T7 expression system. The entire gag—pol region was expressed by recombinant vaccinia virus, as an immunoreactive protein of approximately 55,000 daltons. Neither frame-shifting nor proteolytic processing occurred to a detectable extent. Active reverse transcriptase was made by a recombinant vaccinia virus that contained a pol gene engineered to contain a translation initiation codon at its start. Tat expression was achieved by stlll another recombinant vaccinia virus. These recombinant vaccinia viruses are being used to produce neutralizing antibody, determine cytotoxic T cell targets, investigate proteolytlc processing and transport, study receptor binding, and analyze inhibitors of enzyme activity. w 3 2 A Neutralizing Monoclonal Antibody Reactwe against an External ' Envelope Glycoprotein of HTLV- III/LAV (Human Imunodeflcienc Virus) SHUZO MATSUSHITA*, A. K01T0*, H. S MGR!“ M. RDEERT- GURDFEKW, e'cond Division of Internal Medicine, Kumamoto University Medical School, Kumamoto 860, Japan. "Laboratory of Tumor Cell Biology, National Cancer Institute, Bethesda Maryland, USA. He report the production and characterization of a monoclonal antibody reactive agalnst an external envelope glycoprotein (99120) of human T- -lymphotrop1'c virus type III(HTLV- III/LAV). Gp120 has been associated with virus infectlvity and cytopathology including cell fusion. He inmunized mice with glycoprotein fraction of viral antigens (HTLV- IIIB isolate) and obtained a clone (designated as 54' C), which was secreting monoclonal 196] antibody reactive against 120 kilodalton(kd) molecule of the purified virion in a Western blotting assay. Th1s antibody (designated as 0.58) bound to the surface of HTLV-III infected H9/IIIB cells but not to uninfected H9 cells. 0.58 Inmunopreclpitated 160 kd and 120 kd molecules from extracts of endo- genously radiolabelled H9/IIIB cells. 0.58 crossprecipltated gp160 and gp120 recognized by antibodies in the serum from patients with AIDS. Gp160 and gp120 have been identified as virus encoded envelope gene products of HTLV- IIIB. Neutralizing activity of the antibody was evaluated by infecting the susceptible T-cell line wlth cell free v1‘r1on. 0.58 inhibited the infection of HTLV-IIIB in a dose dependent manner as detected by inmuno- fluorescence assay. He also tested the antibody with syncytia induction inhibition assay using virus producing H9/IIIB cells. Inhibition of syncyt'la formation was observed in the presence of 0.58 antibody. These results suggest that 0.58 antibody reacts with an external envelope protein of HTLV-III. 0.58 antibody may have diagnostic or therapeutic value. WEDNESDAY, JUNE 3 w 3 3 Extensive heterogeneity of HIV genomes i_n vivo. ' MICHAEL SAAG*, J. GIBBONS*, W. PARKS**, E. PARKS**, F. WONG-STAAL***, R.C. GALLD***, G. SHAW*, and B. HAHN*. *University of Alabama at Birmingham, Birmingham, AL, **University of Miami, Miami, FL, and ***Labo- ratory of Tumor Cell Biology. NCI, Bethesda, MD. The AIDS virus, HIV, has been shown to exhibit striking genomic variation when isolates obtained from different individuals are compared. To assess the extent of genetic variation present 15 vivo we isolated HIV from periph- eral blood mononuclear cells of two infected patients (RJS and MPF), generat- ed large recombinant lambda phage libraries, and identified and characterized multiple clones of HIV to search for evidence of genomic diversity ifl vivo. Thirty full-length viral clones from the RJS library and 16 full-length viral clones from the MPF library were obtained and analyzed via restriction endonuclease mapping using Sst I, Eco RI, Bgl II, Hind III, Pvu II, and Pst I. Out of _30 RJS clones, 13 highly related yet genetically distinct genotypes were evident. 0f the 16 MPF clones, 9 highly related yet distin- guishable genotypes were apparent. Certain genotypes were represented by more than one clone and these, in turn, were evident as predominant species on the original Southern blot patterns of infected cellular DNA. HIV passaged in vitro by sequential limiting dilutions requiring multiple rounds of replication did not exhibit similar degrees of genomic variation. These data indicate that (i) extensive genetic variation is generated i2 vivo; (ii) the degree of viral heterogeneity has heretofore been underestimated; (iii) many different viral forms coexit in persistently infected individuals, and thus, "isolates" obtained from such persons for use in the study of HIV biology and immunology, unless cloned, are actually complex mixtures of genetically-distinct viruses. vv 3 4 Full-length and truncated HIV Envelope Polypeptides Produced in ' ' an Insect Cell Expression System Elicit High Titer Neutralizing Antibodies in Animals. *, M.A. Cochran*, B.L. Ericson*, M. O'Shaughnessy**, T. Folks**h M. Martin***, et al., *MicroGeneSys, West Haven, CT, **Laboratory Centre for Disease Control, Ottawa, Canada, *** NIAID, Bethesda, MD. Recent efforts to develop subunit vaccines against the human acquired immune deficiency syndrome (AIDS) have focused on the HIV envelope proteins. Sera from individuals infected with the HIV virus often contain high titer antibodies directed against the viral envelope; however, these antibodies are not protective and usually exhibit low—level neutralizing activity in vitro. This apparent contradiction may in part be due to immunodominant determinants on the envelope being physically separate from important protective and neutralizing sites. Full—length and various truncated forms of the HIV env gene have been inserted into Baculovirus vectors and recombinant glycoproteins of 15,000 to 160,000 molecular weight have been expressed in insect cells. Of more than 600 sera from clinically—diagnosed AIDS patients, all had antibodies that recognized a recombinant gp150 polypeptide using an immunoblot assay. However, when measured by immunoblot, ELISA, and RIP assays many of these same sera had low or Undetectable antibodies against a recombinant glycoprotein (gp120*) which represents more than 90% of the amino—terminal portion of HIV gp120. Animals immunized with gp120' or recombinant HIV proteins that include this region of the envelope produced high titer antibodies that recognized the native viral envelope. Unlike the serum antibodies found in the human AIDS patients we tested, animal sera against these recombinant proteins have high titer antibodies against the portion of the envelope included in gp120*. Also, unlike most sera from AIDS patients, sera from animals immunized with these recombinant envelope proteins contains antibodies that neutralize HIV in vitro at high dilutions. Our data indicate that the apparent lack of a protective immunity in infected humans may in part be due to a misdirected immune response to the viral envelope. w_3,5 CORRELATION or CLINICAL STATUS AND NEUTRALIZING AcnvyvA 0F SERA ** OF PATIENTS INFECTED*HITH HTLV;IIl/HIV. DAVID aLQQm * Fisher R Redfield, D Burke , R Gallo & F Nong- Walter Reed Army Institute of Research, Washington, DC 20307.a 6“Laboratory of Tumor Cell Biology, NIH, Bethesda, MD 20205. Neutralizing activity (NA) in the sera of patients with AIDS, ARC, and the lymphadenopathy syndrome has been described extensively (Robert—Guroff I985, Nciss 1985, Ho 1986, Rasheed 1986). Some investigators have found NA in sera of most patients with ARC (27/27,28/35 - Ho, Guroff) and AIDS (26/31,21/35), whereas others have found few AIDS sera possessing NA (Weiss, Rasheed). The role of neutralizing antibodies In preventing or retarding the progression of disease is of paramount importance in ascertaining the desirable target response of candidate vaccines. Indications that NA may play a beneficial role include the observation that 12/12 clinically stable children with AIDS, but only 1/12 children with a rapidly deteriorating clinical course exhibited NA In the serum (Robert-Guroff). We examined NA in a panel of sera, including a number of serial specimens, fom patients categorized according to the Walter Reed Staging Classification (Redfleld 1986) against a number of viruses derived from molecular clones of HTLV-III/HIV (HXIO, HXBZD, & others). He failed to find a significant correlation of the NA of individual sera against any clone or clones with respect to stage of disease (p=0.578,n=26), and found NA to differ substantially even between very similar strains. These results suggest that determining the clinical significance of the presence of NA against any si.IJl. picnil In :lisely relatgl str1i4; -) HTLV- III/HIV may be difficult. 107 VV.3.5 Group speclflc T cell response to HIV In chlmpanzees lmmunlzed wIth external glycoproteln gp120 of HTLV—IIIB KAL‘JIHE*_KRQHN_I H.G. ROBEY**, A. RANKIr. T.A. PANAVELILr. P.J. FISCHINGER** and R.C. GALLOr. *Laboratory of Tumor Cell Biology, NCI, Bethesda. MD and *iOfflce of the Dlrector, FCRF, NCI, Frederick. MD In a pursult of an effectlve and safe HIV vacolne, chlmpanzees were lmmunlzed wlth purlfled external envelope glycoproteln, gp120 from HTLV-IIIB, and the Immune response towards HIV was monltored. Neutralizing antlbodles were measured wlth the ATH—B assay, based on the cytolytlc effect of HIV on thle target cell llne. Cellular Immune response was followed by T cell proliferation assay, IL-2 measurements and by assessing the capacity of Immune lymphocytes to suppress the expression of HIV ln cultures of Infected autologous cells. All Immune anlmals. but not the controls. showed an antlbody response towards gp120 in Western blot. Neutrallzlng antlbodles were strictly type speclflc to HTLV-IIIB. In contrast, T cell IL—2 production and prollferatlve response to whole heat killed vlrus was group speclflc, seen with three different HTLV—III Isolates (B, MN. RF). The prollferatlng cells were CD-4 or CDB +ve and -ve for B cell markers. When Immune lymphocytes, stimulated wlth gp120 were added Into cultures of autologous lymphocytes Infected In with HTLV-IIIB, the percentage of cells expresslno vlral antigens fell from 5—10* to 0-2%. The above results demonstratlng group speclflc cellular Immune response to HIV even when a vacclne candldate representlng only one Isolate ls used ralses hope for the development of a vacclne agalnst HIV lnfectlon. Blood and Blood Products—Screening and Donor Characteristics vv 4-1 Epidemiologic Characteristics of Blood Donors Who Have Antibody to the Human Immunodeficiency Virus JOHN W. HARD*, S KLEINMAN**, D DOUGLAS***, A GRINDON****, S HOLMBERG*, AIDS Program, *Center for Infectious Disease, Centers for Disease Control, Atlanta, GA, USA **American Red Cross Blood Services, Los Angeles, CA, ***Amer1can Red Cross Blood Services Baltimore, MD, ****American Red Cross Blood Services, Atlanta, GA The demographic and epidemiologic profile of donors with antibody to the human immunodeficiency virus (HIV) is useful for educating donors and studying the prevalence of HIV infection. We examined persons positive for HIV antibody who donated blood from March 1985 to July 1986 at three major U.S. blood centers. of 818,629 donations, 450(0.0SZ) were HIV-antibody-positive; decreasing from 0.07% to 0.04% during the study period. When compared with seronegatives, HIV-seropositive donors tended to be 20-40 years of age (81%), male (88%), and black (47%). HIV seroprevalence among white donors (2/10,000 donations) was lower than among black (31/10,000 donations) (p<0.0001) and Hispanic (9/10,000) (p<0.0001) donors. Seventy-seven percent of seropositive males reported sexual contact with men; 411 were bisexual. Although 44% of seropositive females had apparently acquired infection from heterosexual contact, an equal percentage denied having risk factors for HIV infection. A small but decreasing number of HIV-infected persons continue to donate blood. Black and Hispanic communities may have an increased prevalence of HIV infection in donor populations and/or may have received less information concerning donor self deferral. The high proportion of bisexual men suggests these men may be unaware of their risk for infection. Donor education efforts should be targeted toward minority and bisexual men who may not consider themselves at risk for HIV infection. vv 4 2 Risk of HIV Transmission by Anti-HIV Negative Blood STEVEN KLEINMAN, American Red Cross, Los Angeles, CA Because anti—HIV does not develops until several months after HIV exposure, anti-HIV screening of donated blood is not expected to eliminate HIV transmission via transfusion. We have estimated this risk, by analyzing the results of anti-HIV testing of676,000 donations (dona) over a 21 month period. We have found 17 donors (.003% of dona tested) who have had an anti—HIV(-) dona followed by an anti-HIV(+) done. The intervals separating these dona were a) 3 months (mo) for 8 donors, b) 3 to 6 mo for 5 donors and c) 6 mo for 4 donors. We have tested 4 recipients of anti-HIV(-) blood from 3 Group A donors. Two tested‘anti—HIV(+), having re- ceived blood 2 and 4 months prior to the donor's seroconversion. Donors in Groups A and B gave 16 anti-HIV(—) units; with anassum- ed 50% infectivity rate, we estimate the risk of HIV acquisition from anti-HIV(-) blood to be 1 in 84,000. When compared to anti—HIV(+) donors who did not seroconvert (n= 323), seroconverting donors were less likely to be gay (44% vs. 86%, p=.01) and more likely to have possible heterosexualexposure or no identified risk (44% vs. 9%, p=.01). In late 1986, serocon- verting donors comprised 14% of all anti—HIV(+) donors as compared to 2% in 1985 (p=.002) and 6% in early 1986 (p=.1). Our data sug— gests that the risk of HIV transmission from anti—HIV(—) units may increase unless donor deferral and screening methods are improved. WEDNESDAY, JUNE 3 W4.3 Serologic and Culture Follow-up Study of Anti—HIV Reactive Blood Donors MICHAEL BUSCH*, J.SHIOTA*, M.NASON*, S.SAMBON*, G.VYAS**, H.9ERKINS*; *Iri'vin‘lriemorial Blood Bank , “University of California, San Francisco CA. As of December 1986, 473 donors had been repeatedly reactive by EIA for anti- HIV. Of these, 119 were Western blot positive (WB+), 334 were Western blot negative (WB—), and 20 were considered equivocal (WBeq) based on the presence of weak p24 and/or p55 bands only. We have enrolled 75 of these donors in 3 to 6 month follow—up studies. The initial and follow-up sera were tested by 6 different EIA screening tests for anti—HIV*, by 2 anti—HIV tests using recombi— nant antigens“, by 2 HIV—antigen assays**and by screening for anti-HLA anti— gens. Lymphocytes from WB+ and l‘lBeq donors were cultured for HIV by standard techniques; cells from WB— donors were pooled prior to culture. Oaltures were monitored by reverse transcriptase,in situ hybridization, in vitro DNA amplifi— cation***,inmunocytochemistry, and HIV—antigen assay**.10/10 1VB+ donors (7 with risk factors) were positive by all EIA and recombinant antibody assays on both samples, 2/10 had detectable plasma HIV-antigen, and HIV was cultured from 8/10. 50 WE- donors with both index and follow-up sera were negative by at least 7/8 antibody tests and by both antigen tests; HIV was not detected in pooled cul- tures from these donors; the majority tested had HIA antibodies. Whereas 11/15 WBeq donors were negative on all follow—up testing, 4 had persistent atypical antibody profiles; none were HIV culture positive. These results confirm per— sistent infection of most WB+ donors, and demonstrate the value of follow-up HIV test panels to clarify the status of WB—/eq donors. (Supported by NHLBI: 1-P01—HIB6589—01; I—lB—6—7024) . *Abbott, Genetic Systems, Dupont, Burroughs-Wellcome, ENI, Chiron MAbbott, Chiron ***Cetus W.4.4 Study .DEL N. IQRITSKY", J. C. FRAIIWIONI", M. u. IREIS", D. J. (WWW, and the FDA Blood Dmor Study Eroup, Food and Drug Mninistration", Office of Epidemiology and Biostatistics“, Office of Biologic Research and Review, Pockville, Ml, [SA In Decarber 19%, a rrospective study was begin at 11 geographically differeit blood collection centers in the U.S. to: (1) characterize risk factors of EIA—positive donors; (2) assess the EIA ratio as a predictor of Western blot (NB) status; and (3) determine the ability to isolate virus fran EIA positive patients. Blood specimens fncm EIA positive donors were obtained for T—lymphocyte testing, NB analysis, and viral culture. P5 of Noverber 1986, 658 EIA positive diners were enrolled in the study. Of these, 52 (8%) were NB positive (34 Holes, 18 females), and 5 were culture positive. There were geographic differences in the proportion of EIA positive donors tested positive by the NB test. NB positive donors were more likely to have Ill/18 ratios belorll than were NB negative donors (21 of 45 versus 31 of 521; pkiml). NB positive nnles were nore likely to have had sex with a male than NB negtive nales (18 of 33 versus 4 of 284; p(.0001). NB positive females were more likely to have a history of soiual contact with an IV drug user than )8 negative ferales (3 of 13 versus 2 of 279; p<.(X)l). Analysis of EIA 0i) ratios confirmed that higher ratios were better predictors of a NB positive test. These data indicate that individuals at risk for AIDS continued to donate blood at some centers during this period. Characteristics of EIA and Western Blot Positive Blood mnors in a mlticenter VV.4.5 Human Immunodeficiency Virus (HIV) Cultured from Limiting Dilutions of the Peripheral Blood Mononuclear Cells (PBMC) of Asymptomatic Seropositive Persons P.P. ULRICH*, T. EL—BEIK*,M.P. BUSCH**,E. DONEGAN*,GIRISH N. VYAS*, et 31., *UCSF School of Medicine, San Francisco, CA, **Irwin Memorial Blood Bank, San Francisco, CA. To determine the prevalence of HIV infection in seronegative blood donors, we propose to culture the PBMC from 200,000 donors using pool sizes of 20—200 specimens. In this pilot study the proportion of HIV—infected PBMC from 10 asymptomatic anti—HIV(+) persons has been defined using two separate approach— es: (1) Direct probing of the uncultured PBMC for viral nucleic acids and antigens using i§_situ hybridization (ISH) and immunocytochemistry (IC) analy— ses, respectively; (2) Limiting dilution of the HIV—infected PBMC in cocultures with FHA-stimulated normal PBMC assessed by reverse transcriptase (RT), ISH and IC. The dilutional studies revealed a higher proportion of HIV—infected cells ranging from 1:100 to l:10,000 in comparison with exceedingly rare (less than 1:10,000) HIV—positive cells detected either by direct ISH or IC analyses. Thus, a large proportion of i3 vivo—infected cells are not producing detectable levels of HIV—RNA or proteins without 33 vitro stimulation in the coculture procedure, suggesting that they are latently infected and require 23 vitro stimulation for the expression of viral gene products. Because 10— to 10,000— fold dilution of HIV—infected PBMC coculture with normal PBMC leads to virus recovery, it may be possible for us to grow the virus out of HIV—infected cells from a single individual when mixed with cells from uninfected donors and the pool of 100 PBMC specimens is cocultured in an analogous procedure. (Supported in part by the NHLBI Contract HB-6-7024, Grant P01 HL-36589 andcarried out in conjunction with the SFMHS supported by NIAID Contract N01 AI—32519.) 108 w_4'6 HIV Blood Screening in Africa: Are there no Alternatives? NZILA NZILALBI‘, R.L. COLEBUNDERS”, J.M. MANN“, H. FRANCIS“, K. NSEKA", 37w? W», et 31., *Projet SIDA, n Mama Yemo Hospital, Kinshasa, Zaire, "4* CDC, Atlanta. Screening potential blood donors using the presently available ELISA methods is not feasible in many African countries. To determine the percentage of HIV(+) blood donors which could be excluded by sillple history and physiml exams, we screened for HIV antibody and conducted physical examinations on all 325 blood donors (307 men and 18 women) who donated blood at Mama Yemo Hospital, Kinshasa, between March 3 to April 4, 1986. Sixteen (5t) donors (14 men and 2 women) were HIV(+) by ELISA and Western blot (a rate similar to the one previously observed in the adult population of Kinshasa). No significant differences in clinical findings or exposure to established HIV risk factors between HIV(+) and HIV(-) blood donors were found. Two-hundred and twenty-seven (70%) of 325 units would have been rejected if we had used the following exclusion criteria for screening blood donors: 1) paid donor 2) symptoms suggestive of HIV infection 3) abnormal physical examination 4) history of tuberculosis, herpes zoster or venereal disease within the past year 5) transfusions during the past 5 years 6) receipt of injections during the past 6 months. of the 99 units not rejected by these criteria, one was HIV(+). Because of the persistent blood shortage in Africa such a high rejection rate is unacceptable. Use of a lab test—independent clinical screening profile to reject high risk donors in Africa is not possible. An inexpensive, highly sensitive, rapid, simple machine independant laboratory test for detection of antibody to HIV is urgently needed. Clinical Management—Pulmonary, Pediatric and Neurologic Implications V“ 5 1 Predictive Value of Chest X-rays (CXR) for Lymphocytic Interstitial ' ' Pneumonitis (LIP)/Desquamative Interstitial Pneumonitis (DIP) in Pediatric Patients with AIDS SUSAN MORRISON, E. CONNOR, J. MARQUIS, J. OLESKE, V. JOSHI, B. HOLLAND, ET AL Children's Hospital of New Jersey & UMD-New Jersey Medical School, Newark, NJ LIP/DIP is the most common pulmonary disease in children with HIV infection. Currently, diagnosis requires biopsy (BX) of lung tissue. To evaluate the value of CXR in identifiying LIP/DIP, we compared pre-Bx CXR with pulmonary histopathology. 32 children (15 male, 17 female) with HIV infection underwent lung BX. Mean age at BX was 26.4 mos (3 5-120 mos). Medical records Were re- viewed to determine respiratory status, results of CXR and histopathologic diagnosis. All children presented with respiratory symptoms: rales>retractions cough>clubbing,>rhonchi>wheeze. Histopathologic results follow: 23/32 LIP/DIP; 7/32 Pneumocystis carinii pneumonia (PCP); l/32 Cytomegalovirus (CMV) pneumonia 1/32 nonspecific inf ammatory disease. Pre-BX CXRs were read by one pediatric radiologist. Nineteen of 32 CXRs had linear/nodular pattern (LN); 8/32 conso- lidation, and 5/32 were normal. 0f patients with LIP/DIP, 18/19 had LN, 1/8 consolidation and 4/5 normal CXR. We evaluated LN CXR as a predictor of LIP/ DIP. Sensitivity 0.78, specificity 0.89, positive predictive value 0.95, negative predictive value 0.62. When a second pediatric pathologist blindly read the same CXRs, sensitivity 0.52, specificity 0.78, positive predictive value 0.86, negative predictive value 0.39 These data suggest that LN on CXR in this cohort is highly predictive of LIP/DIP. Further studies will be necessary to confirm these observations. Among HIV infected children with chronic respiratory symptoms, LN CXR may prove sufficient for diagnosis of LIP. w 5 2 Retroviral antigene mia in children with HIV infection. ' I W. BORKO WSKYI K.K RASINSKI, D.PAUL", R.LAW RENCE, T.MOO RE, and S.CHANDWANL NYU-Bellevue Hospital Medical Ctre. New York, N.Y., *Abbott laboratories, North Chicago, IL. A selected group of 35 children with suspected or. documented HIVinfection were tested for plasma HIV antigen using an ELISA antigen capture asay. Plasma from 33 of these were anfigen positive at some time in their life. Antigen oonoenizations were determined in those with AIDS (range of 18—3026 pg/m]; mean: S.D. of 573 i 404); in those with ARC (range of 0-2143 pg/ml; mean: S.D. of 499 i 202); and those without symptomatology (range of 0-175 pg/ml; mean :S.D. of 55 i 213). The lather group had significantly lower HIV antigen levels than those with clinical illneS. Two sets of HIV antibody positive twins were also antigen positive. One of each twin set developed severe HIV related illnessinthe first4 monthsoflife. Within eachsenflieafifected twinhadthe higher titre of antigen. Plasma from 8 high risk maternal-infant (MD pairs was asayed for HIV antigen at the time of delivery. Three antigen positive babies were born in antibody positive but antigen negative mothers. One MI pair ws oonoordantly antigen positive and 1 MI pair was oonoordantly antigen negative. Three antigen positive mothers delivered antigen negative babies, however, 2 of these babies developed antigenemia at subsequent evaluations during the first year of life. These data suggest that (1) prenatal HIV infection may occur; (2) paa‘ve transfer of HIV antigen acros the placenta need not occur; and (3) that natal infection with subsequent antigenemia is Enable. Allthe children from the MIpairs are immunologically and clinically wellto date but continued fiollowup is neoesary. HIV antigen testing of plasma may help explain patterns of vertical izansmisaion of virus and possibly gxedict clinical manifestatiom of disease. WEDNESDAY, JUNE 3 w 5 3 Pediatric AIDS: Neurologic Syndromes ‘ ' Anita L. BELMAN‘, G. DIAWDH, D. DICKSQIH', G. LAN’IDS“, A. RUBINSTEIN“,* , Stony Brook, N.Y.,**AECOM, Bronx, N.Y. U.S.A. To further delineate the spectrum of central nervous system [CNS] syndromes in pediatric patients with HIV infection we have followed 63 infants and children [ages 6 weeks to 13 years) in an ongoing study. Forty—eight children had AIDS and 15 ARC. DIS dysfunction was documented in 61. Manifestations included microcephaly, cognitive deficits, encephalopathies and corticospinal tract signs. The neurologic course in 5 AIDS patients was rapidly progressive. Ten patients [9 AIDS, 1 ARC] had a subacute but steadily progressive course with loss of cognitive skills, progressive long tract signs and mvement disorders. In 28 patients [25 AIDS, 3 ARC] the course was punctuated by plateaus during which no new milestones were attained. Cognitive assessments, revealed mild to severe mental retardation and long tract signs were canton. of these patients, 10 [9 AIDS, 1 ARC] had further neurologic deterioration. Cl‘ examinations revealed marked white matter abnormalities, cerebral atrophy and calcification of the basal ganglia. Ci‘ findings correlated well with recovery of HIV from CSF, and with neuropathologic findings of myelin pallor, inflammatory responses with multinucleated giant cells, calcific vasopathy, and corticospinal tract degeneration. Six patients [4 AIDS, 2 ARC] with plateaus improved but remained mentally retarded. Eighteen patients [7 AIDS, 11 ARC] had a static encephalopathy: moderate to borderline mental retardation with varying degrees of stable motor deficits. CNS lynphoma, cerebrovascular accidents, and CNS infection by conventional pathogens occurred in 8 children [11%]. We conclude that [1] ms involvement with progressive encephalopathy occurs frequently in children with HIV infection; [2] unlike adult AIDS patients, CNS opportunistic infections are uncoumn; [3] In neurologically stable children, morbidity includes mental retardation. These W.5.4 Objective Clinical and Histological Prognsotic Factors for Patients with Fneumocyrtis cannu' Pneumonia and the Acquired Immunodeficiency Syndrome. MAW Wk, PP. OGNIBENE, E.E. LACK, H.C. LANE, A.S. FAUCI, H. MASUR. et at, From theCriticalCare" “ ' I‘ N ‘ ' ofHealth.“ L ‘ MarylandUSA. Pneunwcystis carinii pneumonia (PCP) is the most frequent life-threatening opportunistic infection occurring in r ' with the ., ‘ ‘ ‘ ‘ ‘icirncy s, ‘ (AIDS). In this study, objective clinical and histopathological characteristics were analyzed to assess acute and long term prognostic significance in 43 patients with AIDS and PCP. Survival data, alveolar-arterial oxygen (A~a) gradients, clinically blinded graded chest " L and scored biopsies were ' for all 43 patients. Prognostic factors for survival for the acute episode differed from factors correlating with long term survival following the diagnosis of PCP. Thirty of 43 patients (70%) survived the acute episode. Decreased ability to survive the acute episode of PCP was associated with widened A-a gradients (>3010rr) and more severe abnormalities on initial chest radiographs (p<0.05). Histopathologic specimens were semi-quantitatively scored for severity of 5 separate components of alveolar damage. Cox proportional hazards analysis revealed long term survival following the diagnosis of PCP correlated with the severity of edema on biopsy (2:225, p<0.05), and the extent of A-a gradient at the time of initial diagnosis (z=2.88. p<0.05). Repeat bronchoscopy with re-biopsy was performed in 27 of the 43 patients following an average of 3 weeks of therapy. The persistence of pnetunocysts on follow-up bronchoscopy was associated with significantly decreased long term survival (p<0.05 at 8 months following the diagnosis). Patients diagnosed more recently (July 1985-Iuly 1986) has less severe pulmonary disease at the time of diagnosis (possibly due to earlier, more aggressive evaluation) by the parameters examined in the study and a better prognosis for survival the acute episode (p<0.05) than patients diagnosed earlier (January 1983 to June 1985). Thus, important prognostic information can be derived from objective clinical and histopathologic data obtained at the time of diagnosis and at follow~up bronchoscopy in patients with AIDS and PCP. The improved survival in patiean with less severe disease as measured by these objective parameters suggests that early detection and therapeutic intervention for patients with PCP may improve chances for survival. w_5_5 Serum Lactate Dehydrogenase levels (LDH) in Pneumocystis carinii pneumonia (PCP) in AIDS: Indicator and Predictor of Disease Activity. Possible ILEANA MEDINA, MILLS J, WOFSY C, UCSF School of Medicine, San Francisco General Hospital, San Francisco. CA. USA. Seventy—eight AIDS patients with first episode PCP and moderately well (9596 had po :60) had LDH determinations on days 0,1,3,6,14,18,21, one and 3 months after end of treatment. During the acute phase significant elevation of serum LDH activity was noted in all patients. The LDH followed a specific pattern beginning to increase one week prior to diagnosis; the peak was usually on day 6 to 8 and declined to normal levels within one and a half months. In 67 patients with good outcome (survivors without respiratory failure) the mean initial LDH was 355.9 U (150-520). Eleven patients had a poor outcome (respiratory failure or death w/o intubarion); the initial LDH was significantly higher in these patients with a mean value of 710‘(450—977). All the survivors with or without respiratory failure showed a decline in LDH levels after 5—6 days of therapy. All nonsurvivors had a progressive increase in their LDH levels after day 6 to 8. LDH isoenzymes were performed in 19 patients. In all but 2 L133 fraction 3 was abnormally elevated {’f2696]. These findings suggest that serum LDH activity is a useful indicator of the severity of PCP in AIDS patients and that it may be utilized to predict disease course and monitor response to treatment. 109 VV.5.5 Serum Glutamic Acid as Potential Marker for Pneumocystis carinii Pneumonia in AIDS. JOHN ROBOZ, D. KAPPATOS, D. MILDVAN, M. CHUANG, AND J.F. HOLLAND, Mount Sinai School of Medicine, New York, NY, 10029. Current diagnostic techniques, open lung biopsy and bronchoscopy, are highly invasive and cannot be used to monitor therapy. Objective: to find a circulat— ing serum marker that could be used repeatedly for both diagnosis and monitor— ing. Identification: computer comparison of gas chromatographic—mass spectro— metric (GC—MS) profiles of the trimethylsilyl (TMS) derivatives of aqueous extracts from PCP invaded lungs and normal lungs revealed a potential marker, the presence of which was also confirmed in PCP serum samples. The marker was identified as L—glutamic acid (glu) by both low and high resolution mass spectrometry (electron and chemical ionization) using TMS and acetyl—methyl derivatives and also by using L-glutamic decarboxylase to remove glu. Quanti- fication in serum: GC-MS (int. std.: deuterated glu); analyses were also made using colorimetry and liquid chromatography. Glu Conc. >108 uM (mean of normal +25.d.) considered elevated. Of 103 patients (70 coded) containing 73 indepen— dently confirmed PCP cases (45 coded) sensitivity: 81%, specificity: 86%. 0f 22 patients with blood taken within 3d of bronchoscopy: 15 of 20 with proven PCP were positive. Two true negatives and 5 PCP cases were negative. No false positives were found. This suggests that invasive testing need be performed only in those who do not have elevated glu conc. Preliminary results revealing concurrent changes in serum glutamine (gln) cone. suggest that changes in glu may result from physiological changes caused by PCP, resulting in an altered glu/gln ratio. (Supported by AIDS Institute, State of New York, and the T.G. Martell Memorial Foundation for Leukemia and Cancer Research). Roundtable Discussions W.6 Heterosexual Transmission of the AIDS Virus Dr. Tim Dondero Centers for Disease Control Atlanta, Georgia Panel Organized By: H. Hunter Handsfield, Seattle-King County Department of Public Health and University of Washington, Seattle, Washington Peter Piot, Institute of Tropical Medicine, Antwerp, Belgium Robert Redfield, Walter Reed Army Institute of Research, Washington,'D.C. Niel Steigbigal, Montefiore Medical Center, Bronx, New York Rand Stoneburner, New York City Health Department, New York, New York W.7 Vaccine Related Issues Panel Organized By: Gerry Quinnan Food and Drug Administration Bethesda, Maryland Patricia Fultz, Centers for Disease Control, Atlanta, Georgia Fritz Deinhardt, Max v. Pettenkofer-lnstitut, Munich, Federal Republic of Germany Dani Bolognesi, Duke University Medical Center, Durham, North Carolina John La Montague, NIAID, Bethesda, Maryland Richard Kaslov, NIAID, Bethesda, Maryland WEDNESDAY, JUNE 3 W.8 Legal, Ethical and Public Policy Issues: The American Perspective Gene Matthews Legal Advisor Centers for Disease Control Atlanta, Georgia Panel Moderator: Earl Shelp, College of Medicine, Houston, Texas June Osborn, University of Michigan, Ann Arbor, Michigan Carol Levine, The Hastings Center, Briarcliff Manor, New York Harold Edgar, Columbia University School of Law, New York, New York Joan 3. Campbell, World Council of Churches, New York, New York Alvin Novick, Yale University, New Haven, Connecticut Larry Gostin, American Society of Law and Medicine, Boston, Massachusetts W.9 Assuring an Adequate Blood Supply of Healthy Blood Donors in This Age of AIDS Gerald Sandler American Red Cross Washington, D.C. Panel Organized By: Gordon T. Archer, Australian Red Cross, Sydney, New South Hales, Australia Richard E. Counts, Council of Community Blood Centers and Puget Sound Blood Center and Blood Program, Seattle. Washington Lewellys F. Barker, International Society of Blood Transfusion and American Red Cross National Headquarters, Washington, D.C. Joseph R. Bove, American Association of Blood Banks and Yale-New Haven Hospital, New Haven, Connecticut Anthony F.H. Britten, League of Red Cross and Red Crescent Societies, Geneva, Switzerland Jonathan Mann, World Health Organization, Geneva, Switzerland W.10 Meeting Gaps in Medical Needs Reed Tuckson Commissioner of Public Health for the District of Columbia Washington, D.C. Panel Moderator: Joseph A. Nkwanyuo, Internal Medicine, Baltimore, Maryland Elmer w. Smith, Health Care Financing Administration, Baltimore, Maryland Paul A. Volberding, San Francisco General Hospital, San Francisco, California ’ James M. Graham, Whitman—Walker Clinic, Inc., Washington, D.C. A Representative of the Robert wood Johnson Foundation 110 Poster Session “IP1 Enhanced In Vitro Suppression of HIV Infectivity by a Combination ' of Nucleoside Analogs LIONEL RESNICK*, A. M. MIAN**, *Mount Sinai Medical Center, Miami Beach, FL, **University of Miami School of Medicine, Miami, FL. Azidodeoxythymidine (AZT),a nucleoside analog with anti-HIV reverse trans- criptase (RT) activity in vitro has been found to have clinical toxicity that limits drug dose. 6 thioneazaguanine (6TDG),a nucleoside analog with anti- viral properties,was tested individually and in combination with AZT to deter- mine if HIV inhibitory activity occurred in Vitro. A drug screening assay was developed to evaluate the antiviral activity of compounds at drug levels causing no target cell cytotoxicity over a broad range of multiplicity of in- fectious units (M01) and over prolonged periods of time. Evidence of HIV in- fection and replication in culture was monitored by RT assays,immunofluores- cense cellular assays with anti-p24 monoclonal antibody and cell-cytopathic effects. At an MOI of I,AZT (Zug/ml) and 6TDG (0.3u9/ml) individually exhibi- ted suppressive effects on HIV expression throughout the 20-day experiment. The HIV infected culture without drug (control) revealed the presence of HIV on day 10. At an MOI of 100,HIV replication was detected at day 10 with 6TDG (0.3ug/ml), day 20 with AZT (Zug/ml) and day 14 with AZT (lug/ml) (control— presence of HIV on day 7). The utilization of AZT (lug/ml) and 6TDG (0.1ug/ml) in combination,at lower doses,achieved complete suppression of viral replica- tion at an MOI of 100 over the 20-day period. The combination of nucleoside analogs,AZT and 6TDG,appear to enhance the inhibition of HIV infectivity in Vitro. Combination antiviral therapy may be important in maintaining efficacy at non-toxic drug levels. WP,2 lg Vitro Infection of Glial Cells with Diverse HIV Isolates JONATHAN HEBER*, E. ROBEV**, R. AXEL**, R. NEISS*, *Chester Beatty Laboratories, Institute of Cancer Research. London, **College of Physicians and Surgeons, Columbia University, New York, 10032. The susceptibility to HIV infection of 6 established malignant glioma cell lines was investigated, using a diverse range of characterised HIV isolates. The results were contrasted with the susceptibility of 50 primary cultures from malignant glioma tissue. One line, U 138.MG (Hestermark) was susceptible to infection with diverse characterised HIV-1 and HIV-2 isolates, including HIV RF, HIV IIIb, HIV RUT and LAV-2. Infected cells do not demonstrate indirect innmno- fluorescence for HIV antigens, and cultures were negative for antigen ex- pression (Dupont), and only occasionally positive for reverse transcriptase; however, infected cells consistently produced syncytia with a T—cell line, C8166, which were specific for HIV. There was no evidence of the CD4 antigen on the cell surface, or in the cytoplasm, in infectable cells by immunofluorescence with several monoclonal anti-CD4 antibodies. However, CD4 mRNA was detected in these cells by northern blot with a CD4 probe; even so, it was not possible to block infection of glial cells with anti-CD4 monoclonals. The infected glial cells were not lysed by HIV, and grew normally. The possibility remains that HIV infected glial cells may be a target for lymphocyte cytotoxicity ifl Vitro, and data on this will be presented. was Persistent H'I'LV-IIIb end LAV Infection in chimpanzees. Its Effect on Virus Biochemistry and Serology. PETER L. NARA’, L.0. ARTHUH”, ".6. HOBEY‘, P.J. FISCHINGBR‘, and D.M. ASHEH*“,‘0ffice of the Director, Virus Control Unit, MCI-Frederick Cancer Research Facility (FCRF), Frederick, MD 21701, "Program Resources, Inc., NCI- FCRF, Frederick, MD 21701, NINCDS, NIH, Bethesda, MD 20205. USA. The chimpanzee has been shown to be capable of persistent infection by HTLV III/LAV. This state of persistent viral infection can thus be utilized for biochemical and serological investigations. Three chimps were given either HTLV—IIIb—infected cells (#525), HTLV—IIIb virus only (#525), and LAV from a previously infected animal (#524). Virus was reisolated from all animals 1 1/2 years later and purified viral envelopes were compared to the original virus inoculum by oligo—chymotryptic peptide mapping methods. In the 2 cases where the original isolate was mapped (HTLV-Illb), a difference in 2 peptides was detected in the reisolsted virus. Viral maps from the LAV animal were similar to the reisoleted HTLV-IIIb maps suggesting a host-induced modification. All animals developed progressively high titered, initially type-specific, neu- tralizing antibody response which progressively broadens after 2-4 months to a group—specific response. Maximal titers were found between 1 and 2 years following virus inoculation. Also, virus reisolated from each chimp was neutralized by each others sera, as well as their own. All animals” sers contain antibodies which recognize p24, Ag 121, gp120, and exhibit antibody- dependent, complement-mediated cytolysis (ACC). Human sera from healthy AIDS and ABC patients were found to be negative for ACC. Thus, it appears that chimpanzees persistently infected by one virus isolate undergo an i3 yigg expression to yield alternate form(s) of the envelope which leads to a group- specific response. Research sponsored, at least in part, by the NCI, DEBS, under Contract Nu-ber N01-CO-23910 with Program Resources, Inc. WEDNESDAY, JUNE 3 WR4 Membrane Inmunoassays for the Detection of HIV Antibody and Antigen CELIA M. CRANE and KEVIN J. REAGAN, Medical Products Dept., E. I. Du Pont de Nemours and Co., Inc., Glasgow Research Laboratory, Wilmington, DE 19898. The likelihood of HIV transmission through donor blood has been greatly reduced by the introduction of enzyme immunoassay: (EIA) which monitor the presence of antibody to virus. In addition to an antibody assay, Du Pont has released as a research product an EIA designed to detect HIV core antigen. These assays are highly sensitive though their requirement for automation limits their application to modern clinical or research settings. Studies were initiated to adapt several methods to membrane surfaces designed to function without automation yet provide sensitive and specific detection of HIV antibody and antigen. HIV antibody was monitored using two recombinant proteins, one specific for a portion of the viral envelope (gp41) and the other for core (pl7,24,15). The recombinant antigens were placed on separate areas of a nitrocellulose strip. Diluted patient samples were incubated with the strips. and bound antibody was detected using alkaline-phosphatase-conjugated anti-human antibody and bromo- chloro-indolyl phosphate/nitroblue tetrazolium substrate. Excellent sensitiv- ity was noted in a 40 minute assay using a visual read-out. HIV antigen was monitored by sandwich immunoassays on nylon membranes. Two assays were devised, one to detect the major core protein, p24, and the other to detect envelope glycoproteins, gp120 and gp41. Measurement of p24 has been the more sensitive method with a detection limit of approximately 0.3ng/ml of p24. Nylon membranes having a large surface area permit a high concentration of capture 196 as well as dynamic sample flow-through. WB5 Development of clonal cell lines from Kaposi's sarcoma (KS) lesion (AIDS—KS) and their biological properties ZAKI SALAHUDDIN*, S. NAKAMURA*, P. BIBERFELD *, and R. GALLO*. * National Cancer Insfifufe, Betheda, VD. ** Karolinska Institute, Stockholm, Sweden. AIDS-KS is an aggressive disease of young people and has a multifocal and histologically complex nature. So far, its origin and pathogenesis remain unknown, in part due to the lack of in vitro long-term culture system to pro— duce large quantities of cloned cells. as report the isolation of KS cells, their long—term culture and their morphological and biological characteris- tics. They were isolated and cloned from KS lesions obtained fron the lung of AIDS-patients. These cells gave only a low response to classical endothelial cell growth factors. However, conditioned medium fron HTLV-II-transformed cell lines(HTLV-II-CM) supported the growth of KS cells for over 9 months and large quantities were harvested for study. Immunocytologically and morphologi- cally, they shared the properties of lymphatic endothelial cells. CM from these KS cells(KS-CM) were tested for activity on nonnal endothelial(NE) cell growth, IL—l, colony stimulating activity and other growth factors. KS-CM pro— moted NE cell growth and it also had some effect on KS cell growth. NE cell growth promoting activity in KS-CM differes from HTLV-II—CM. Molecular analy- sis suggested similarity bebween basic fibroblast growth factor and KS—CM but not with HTLV-Il-CM. It also contained lL-l-like factor as measured by thyme- cyte co-mitogenic assay. Because IL-l could stimulate KS cell growth, it was suggested that a autocrine mechanism of the IL-I-like factor was related to KS cell growth. KS—CM has a potent neo-angiogenic activity. KS cells also induce KS like lesion, when they are transplanted in athymic nude mice. No viruses have been detected in cultured KS cells. In summary, our results are consistent with the idea that pathogenesis of KS may depend on the production and response to soluble factors. WR6 Role of synthetic peptide analogs of HIV on T—lymphocyte cells and on virus replication. 5. CUMMING", D. MCPHEE*, D. STAPLETON**, B. KEMP** and R. DOHERTY". *Virology Department, Fairfield Hospital, Fairfield 3078, and **Department of Medicine, University of Melbourne, Repatriation General Hospital, Heidelberg 3081, Australia. Biological activity of HIV proteins is being studied by examining the effect of synthetic peptide analogs on lymphocyte proliferation and on virus replication in TA+ cell lines. Synthetic peptides from gp120 (as 2—13, 55-65 and 192-200), from gpAl (aa 582-596, 579—600, 659-670, and 766—778), and from ptat (aa 66—58 and 60-72) were synthesized using the Merrifield procedure with COOH«terminal cysteine residues. One gp120 peptide (192—200) has been found to be a potent inhibitor of virus replication for isolate HTLV—IIIb (PNAS, §§, 925h-8, 1986) and a gphl peptide (582—596 and extended peptide 579-600) has been found to be highly antigenic (PNAS, §§, 6159-63, 1986). Additionally the latter peptide has sequence homology to other retroviral transmembrane proteins that are known to suppress lymphocyte proliferation (Science, 229, 453-5, 1985). Our results indicate that peptides 582-596 and 579-600 both suppress lymphocyte proliferation with all other peptides having little or no effect. Replication in T4+ cell lines of an Australian isolate, in the presence of the above peptides, was compared with that of HTLV-IIIb. The results indicate variable effects on virus replication. Thus these regions in gp120. gpél and/or ptat proteins may play important roles in virus replication at least 'in vitro'. 111 WB7 MT-A Plaque Assay Distinguishes HIV Serotypes and Distinct Biologic Isolates MASATOSHI TATENO, C. CHENG-MAYER, J.A. LEVY, Cancer Research Institute, UCSF School of Medicine, San Francisco, CA. The MT-A plaque assay, as described by Harada et al (Science 229:563, 1985) was used to quantitate infectious HIV. Six out of gourteen HIE isolates tested formed plaques. Titers were in the range of 5 X 10 to 2.5 10 pfu/ml. Plaque formation did not correlate with ability of the fourteen HIV to replicate in established cell lines. Studies with the plaque-forming HIV isolates indicated the presence of neutralizing antibodies in many HIV-positive individuals. Neutralizing antibody titers as determined by the MT—4 plaque assay correlated well with those determined by reduction in reverse transcriptase acitivity in infected cells. The presence of these antibodies did not reflect a particular disease state. During this study, it was noted that HIV F did not form plaques in MT-A cells. However plaqueswere induced by botfi fiIvSF , an isolate obtained 5 months later from the same individual yielding fiivSFZ’ and HIV FZA’ an isolate recovered from a chimpanzee inoculated one year previously with HIVSFZ. The results of these studies suggest biologic changes in HIV over time in the same individual and in a new host. Comparative serologic studies and restriction enzyme and envelope gene analyses of HIVSFZ’ HIVSF , and HIV should indicate the extent of antigenic and molecular changes égat have occurred in these HIV isolates. SFZA was Cyclosporine A (CSA) prevents infection of healthy T cells by HIV but has no effect on pro-infected cells MARK A. WAINBERG, N. BLAIN, Lady Davis Institute, Jewish General Hospital, Montreal, Canada. In order to determine the effect of CSA on ability of HIV to infect healthy peripheral blood lymphocytes (PBL's), these cells were stimulated with FHA for 48 hr, after which they were co-incubated with an excess of the HTLV-IIIB strain of HIV, in the presence of polybrene (Zug/ml). CSA (0.5ug/m1) was added to cultures after either 2 hr, 24 hr, or 72 hr. Infection of cells was monitored both by an indirect immunofluorescence assay, using monoclonal antibodies against viral proteins p15 and p24 and by measuring reverse transcriptase activity. In control cultures, untreated with CSA, the percentage of positive cells after 5 days was about 252. The addition of CSA at 2 hr completely prevented viral infection in PBL's over 21 days. However, if the addition of drug was delayed either 24 hr or 72 hr after infection, the results showed that 1% and 152 of PBL's became positive for viral antigens after 12 days and 5 days respectively. CSA had no effect on the ability of HTLV-III -infected T cell line, H-9 cells, to replicate or to express viral antigens. HIV was able to infect PBL's obtained from each of 6 kidney allograft recipients on long-term CSA anti-rejection therapy, as long as CSA was not included in the culture medium. In addition, we were able to repeatedly isolate HIV from patients entered into a Canadian therapeutic protocol, in which CSA was used to treat AIDS patients with advanced disease. Supported by Health and Welfare Canada and by the Medical Research Council of Canada WP9 Correlation of Serum HIV Antigen Detection with Isolation of HIV from Patients ' with AIDS and Patients at Risk for AIDS. . B NNIE DITTEL’, L.FALK”, D.PAUL”, LSPEAR‘, H.KESSLER‘, and A.LANDAY‘. *Rush Medical College, Chicago, IL and :‘Abbott Laboratories, North Chicago, IL. HIV isolation was attempted with peripheral blood mononuclear cells (MNC) from AIDS patients (n=4l), ARC patients (n=28), HIV seropositive asymptomatic homosexual males (AHM) (n=37), and HIV seronegative AHM controls (n=29). All samples were obtained from individuals who were hospitalized or seen by a private physician. Cultures were performed using peripheral blood MNC from healthy heterosexuals which were stimulated with FHA (FHA—MNC) and cocultured with MNC of the above patient groups after addition of IL-2 and polybrene to the medium. Virus was isolated from 39 of 41 AIDS (95%), 16 of 28 (57%) ARC, and 22 of 37 (59%) asymptomatic antibody positive homosexual males. All control patients were culture negative. The association between HIV-Ag detection and virus isolation is shown in the following table: l r R ul Arn P ' t r HIV AID AHM 132 4 Am Pos Heq Pos Neq Pos Neg + 18 0 12 3 15 2 — 21 2 4 9 7 I; There was no significant association noted between detection of HIV-Ag and virus isolation among AIDS patient. In contrast, there was a significant association (5050.01) between HIV—Ag in serum and positive cultures among ARC and AHM patients. Detection of HIV-Ag in the serum of patients with ARC or asymptomatic HIV antibody positive individuals may be predictive for isolation of HIV from MNC. WEDNESDAY, JUNE 3 wp1o DETECTION OF DIFFERENT TYPES OF OLIGOSACCHARIDES IN ENVELOPE I GLYCOFROTEINS 0F HIV/HTLV-III VIRUS C.A. Abel, M.D., C.H. Mielke, Jr., M.D., and J.C. Klock, M.D. Institute of Cancer Research, Medical Research Institute, San Francisco, CA. The envelope (Env) structures of the HIV/HTLV-III virus (gp160,gp120) have been defined as glycoproteins on the basis of their ability to bind Lens Culinaris Lectin (LCL), incorporate radiolabelled glucosamine in cell cultures, and display a significant reduction in their molecular weight following treatment with endoglycosidases. The deduced amino acid sequences of several viral isolates indicates the presence of 28-30 potential N-linked glycosylation sites (Asn-X-Ser/Thr) within gp160; of these, approximately half are located with invariant regions of the polypeptide chain. The purpose of our experiments was to determine what types of oligoaaccharidee are linked to HIV/HTLV-III Env glycoproteins. Cell-free supernatants obtained after centrifugation of cultures of HIV/HTLV—III infected cells at their peak of reverse transcriptase activity, and Env glycoproteins isolated by micro immune—affinity chromatography, were subjected to SDS-FAGE, electroblotted onto nitrocellulose, and probed with a panel of biotinylated lectins of well defined carbohydrate binding specificity. Lectin binding was determined before and after exo- and endoglycosidase treatment of virus components. Gploo and gp120 bound Con A, LCL, FSA, FHA-E and LFA. This binding patterns suggests that oligomennosyl, as well as nonbisected fucosylated and sialylated biantennary oligosaccharides are present in both glycoproteins. Binding of FHA-L was weak. Binding of PNA to gp120 after desialyiation, and absence of binding after alkaline hydrolysis suggests the presence of sialyleted O-linked Gal—GalNac sequences within this glycoprotein. Binding of lectlns to gplol was consistently weak. Experiments are in progress to study the possible role of gp120 oligosaccharides in the binding of HIV/HTLV-III to the TA receptor molecule. WETI Genetic Variation of the AIDS Virus I_n Vitro JOSEPH GIBBONS*, W. PARKS**, E. PARKS**, E. *University of Alabama at Birmingham, Birmingham, AL; Miami,FL Human immunodeficiency virus (HIV, HTLV-III/LAV) isolates from different individuals have been found to exhibit striking genetic diversity. It is unclear, however, to what extent these sequence changes reflect variation that has occurred i_n m as compared to in vitro. To address this question, we compared the restriction pattern of HIV from uncultured brain tissue with that of virus from the same brain tissue cultured in peripheral blood lymphocytes and H9 cells. 12/12 restriction fragments generated by A differ- ent endonucleases were identical in the cultured and uncultured specimens. A second approach to assessing the relative rate of viral genetic variation 1E vitro was to subject virus to repeated rounds of cell-free terminal dilution followed by expansion in H9 cells, thus forcing multiple rounds of viral replication and reverse transcription. Sequential terminal dilutions of virus isolate WMJ-l over a five month period gave rise to five virus iso- lates, WMJ-1(TD-1) to WMJ—1(TD—S). WMJ-1(TD-5) infected H9 cell DNA had an identical HIV restriction pattern to the original parental isolate WMJ-i for all 6 restriction enzymes tested (Sst I, Eco RI, Hind III, Bgl II, Fst I, Fvu II) indicating that the predominant viral species had not changed. Further- more, 10 out of ll full-length HIV/A phage clones derived from “Md-1(TD-S) were identical to the parental WMJ-l isolate. These data demonstrate that the striking genetic diversity observed in independent HIV (HTLV-III/LAV) isolates results from mutations that have occurred 33 vivo, not 12 vitro. Since the magnitude of the genetic changes that occur i2 vivo is much greater than that observed 13 vitro, it is possible that genetic variation may be selected by host immune pressures. HAHN*, G. SHAW*. **University of WPJZ Epitope Mapping of the HIV gFlZO Antigen Using Monoclonal Antibodies and Lambda gtll Library Screening G.R. NAKAMURA*, C. SHIMASAKI**, D. DOWBENKO***, T.J- GREGORY**, L.A. LASKY***, ERIC J. FATZER*, et al., Genentech, Inc., 460 Pt. San Bruno Blvd., South San Francisco, CA, USA Although a small number of epitopes of the HIV envelope antigen have now been mapped, there remain several critical regions of the molecule whose locations are unknown. In particular, epitopes which may be responsible for interaction with the virus receptor, the C04 antigen, have yet to be delineated in the envelope protein. In order to begin such an analysis, a collection of monoclonal antibodies against the gp120 antigen has been developed. Seven monoclonal antibodies (MAbs) from heterologous rat-mouse , and ten MAbs from mouse—mouse hybridomas were generated against a recombi- nant form of the gp120 glycoprotein (rgp120) from the human immunodefi- ciency virus strain illb. All seven of the rat-mouse MAbs, and three of the mouse-mouse MAbs, reacted with intact rgp120 and a 75,000 Dalton amino terminal proteolytic fragment by Western blot analysis. In addition, three other mouse-mouse MAbs bound to a 55,000 Dalton proteolytic fragment corresponding to the carboxy-terminus of rgp120. Competition analysis of the various MAbs has allowed them to be placed into seven different groups. In order to map the location of the epitopes recognized by these MAbs, a collection of small, random DNA fragments from the gp120 gene has been incorporated into a lambda gtll expression vector. Screening of this library with the various MAbs, as well as with polyclonal serum from patients, has resulted in the mapping of epitopes recognized by these MAbs as well as by the immune system of an infected individual. The location of these various epitopes will be presented. 112 WR13 Use of PHA Can Interfere with Efficient Recovery of HIV From Feriperal Blood Mononuclear Cells. BARBARA MICHAELIS, C.M. WALKER, H. LEGG, M. WHALEN, AND J.A. LEVY, Cancer Research Institute, University of California, School of Medicine, San Francisco. CA. Methods for isolation of the human immunodeficiency virus (HIV) from peri- pheral blood mononuclear cells of HIV-seropositive individuals vary among laboratories, but usually involve mitogenesis with phytohemagglutinin, or addition of normal allogeneic PMC from HIV seropositive blood donors. Using PHA as a stimulus, we can routinely recover HIV from the PMC of about 502 of healthy HIV—seropositive subjects, and from 75—902 of those with AIDS or ARC. We have undertaken studies to determine if FHA and allogeneic lymphocytes function equally well in virus isolation, or if some combiation of the culture methods should be used to optimize recovery of HIV. Two sister cultures established from the PMC of 11 HIV seropositive subjects received either (1) medium containing FHA (3ug/ml), or (2) medium without FHA, but with 6x10 normal human PMC previously stimulated with FHA. All cultures were passed without FHA every 3-4 days and received normal PMC after day 9 as required. Culture fluids were assayed after day 7 for reverse transcriptase activity. Virus was recovered from 6 of the 11 subjects. of these, 5 released virus only when their PMC were cocultured with normal PMC and not FHA. One subject released virus when his PMC were cultured with either PHA or normal PMC. These results suggest that recovery of HIV from seropositive subjects can be improved by co-culturing the PMC with allogeneic PMC from HIV—seronegative blood donors without the use of FHA. It is conceivable that CD4+ cells in the normal FMC o ulta'on ac as addi ional tar ets for viru re 11 ation or that the re- gegce of FHA in the cu ture supefnatant stimulateg t e generation of cells with antiviral activity. These possibilities are under investigation. WR14 Identification of HIV Serotypes with Distinct Patterns of Sensitivity to Serum Neutralization CECILIA CHENG—MAYER, J.M. Homsy, J.A. Levy, Cancer Research Institute, UCSF School of Medicine, San Francisco, California The Human Immunodeficiency Virus (HIV) displays a high degree of genetic variation, especially in the gp120 domain of the 221 gene. To determine whether this genomic heterogeneity leads to the expression of different independent HIV serotypes, twelve HIV—positive sera were tested for their ability to neutralize infection of peripheral mononuclear cells (PMC) by a panel of diverse HIV isolates. The HIV used included those from the United States, Dominican Republic and Africa. Some of these HIV were isolated from nerve tissues. Results show that the A) those neutralized by isolates can be grouped into three distinct classes: all sera tested at high titers, B) those neutralized by only certain sera at low titers, and C) those neutralized by none of the sera. No correlation was observed between the ability of patient's sera to neutra- lize HIV infection and serum anti-En! or IFA titers or severity of disease. The data define the presence of distinct HIV serotypes and suggest that for vaccine development, further characterization of HIV serotypes and their use in combination may be required. Trans-activation by STLV-3 and HTLV—4 P.15 vv GREGORY A. VIGLIANTI, V.HIRSCH, H. KORNFELD, N. RIEDEL, AND J.I. MULLINS, Dept. of Cancer Biology, Harvard School of Pub— 1ic Health, Boston, MA. Simian T-lymphotropic virus type—3'(STLV-3) and human T-lympho- trepic virus type—4 (HTLV-A) are closely related to the human im— munodeficiency virus (HIV) yet evidently differ from HIV in their pathogenic potential in their respective hosts. As a step in un- derstanding the biological differences between HTLV-A/STLV-3 and HIV we examined whether HTLV-4 and STLV-3 encode transactivator' (tat) proteins which mediate gene expression from their long term- inal repeats (LTRs). Chimeric genes were constructed consisting of HTLV-A or STLV-3 LTRs joined to the protein coding region of the bacterial chloraphenicol acetyltransferase (CAT) gene. Additional— ly, DNA fragments containing either the first exon or both exons of the putative tat genes of both HTLV—la and STLV—3 were placed under the transcriptional control of the SV40 early gene promoter. Co—transfection experiments and subsequent CAT enzyme assays and Northern blot analyses indicated that, like HIV, both HTLV-A and STLV—3 encode trans-acting regulatory factors which increase gene expression from either HTLV-A or STLV-3 LTRs. However, unlike HIV, trans—activation by HTLV-b or STLV—3 is greatly enhanced by sequ- ences extending beyond the first coding exon of the tat gene. The tat—mediated increase in gene expression was reflected by concom- minant increases in both CAT RNA and protein. WEDNESDAY, JUNE 3 WE16 Genetic Analysis of £i_s and trans Elements Involved in the Regula- of HTLV-III. ERNEST F. TERWILLIGER*, CRAIG ROSEN*, JOSEPH G. SODROSKI*, and WILLIAM A. HAS- ELTINE**. Dana-Farber Cancer Institute, Dept. of Biochemical Pharmacology, Har— vard Medical School, and **Harvard School of Public Health, Dept. of Cancer Bio- logy, Boston, MA. The genomes of HTLV-III and closely related viruses are unique in their pos— session of several novel genes not found in any other retroviruses. These inv clude the £§£_and g££_genes, whose products play crucial roles in regulating viral protein expression, and the s E and 3' g££ genes, whose functions remain unclear. Recently an additional novel gene has been identified in HTLV—III, encoded within an open reading frame designated the R region — preceeding the £g£ gene. Recent results will be presented from an ongoing systematic mutation— al analysis of elements involved either gig or trans in the regulation of the virus. Regions being investigated include the 3' EEE gene, the R region, and the EEE gene product. WPJ7 Differential Recognition of HTLV-III/HIV Envelope Antigens is Correlated with clinical Outcome TUN-HOU LEE*, R. REDFIELD", M.-J. CHOU*, J. ALLAN*, D. BURKE“, M. ESSEX*, et a ., Harvard School of Public Health, Boston, MA, MHalter Reed Army Institute of Research, Washington, DC. Two types of antigenic domains are identified on HTLV-III/HIV envelope protein, gplZO. One, designated gp120(N), requires the presence of disulfide bonds to maintain their antigenicity, while the other, designated gp120(R), does not. Analysis of 135 coded serum samples from patients who have been clinically staged by a Halter Reed staging classification system reveals that patients with AIDS (NR6 stage) are three times less likely to have antibody to gplZO(R) than patients with just lymphadenopathy (HRZ stage). In contrast, all 135 patients had detectable antibody to gp120(N). This observation raises the possibility that differential response to different antigenic epitopes may have prognostic value and that gp120(R) may be more likely to elicit protective immunity than the more native gp120(N). WR18 Approach to Development of an AIDS Vaccine Using HGP-30, a Synthetic p17 Peptide Analogue ALLAN L. GOLDSTEIN‘, P.H. NAYLOR*, P. SARIN**, C.J. GIBBS***, B ZOOK**, S.S. WANG;*** et al. *The George Washington School of Health Sciences, Washington, D.C., **The National Cancer Institute, Bethesda, MD., ***The National Institute for Neurological Diseases, Bethesda, MD, ****Alpha 1 Biomedicals, lnc., Washington, DC. Antisera against HGP-30 (HIV synthetic p17 gag peptide analogue - 30 amino acids), prepared by solid phase peptide synthesis, as well as antisera against thymosin a (Tol ) are highly effective in neutralizing the AIDS virus lg vitro. Neufralization is defined as inhibition of viral growth in H9 infected human cells assessed both by measurement of reverse transcriptase and viral antigens (p17 and p25). HOP-30 contains a region of homology with p17 from position 86 to 115. The HGP'3O antisera is not significantly cross-reactive with To . "hen coupled to KLH, the antigen is highly immunogenic and effective in generating serum antibodies to HOP-30 as well as HTLV-IIIB p17. Used with either alum or complete Freund's adjuvant, the vaccine is immunogenic but not toxic in mice, rabbits, dogs and primates. The demonstration that antibodies to HOP-30 are neutralizing and cross-react with p17 provides a new and potentially more specific candidate for development of an AIDS vaccine. Using HGP—30, a small synthetic peptide, as the immunogen in a vaccine against AIDS offers the advantages of l) ease of large-scale preparation and uniformity of a chemically defined product, 2) safety; does not require use of killed or attenuated virus, virus-infected cells or genetically manipulated products, 3) overcomes the problem of genetic drift; in contrast to env proteins the p17 epitope identified is highly conserved.(Supported by grants and/or gifts from the NCI (CA24974), Alpha 1 Biomedicals, Inc-, and Viral Technologies, Inc.) 113 WP_19 SIV/Delta Induced SAIDS in Rhesus Monkeys: Pathogenesis of Cultured Isolates of Rhesus and Mangabey Monkey Origin. MICHAEL MURPHEY-CORB, G.B. EASKIN, L.N. MARTIN, E.A. WATSON, Delta Regional Primate Research Center, Tulane University, Covington, LA. U.S.A. As a part of a tissue transmission study, we documented the association of an HIV-related retrovirus, SIV/Delta, with simian AIDS (SAIDS) in rhesus monkeys. Indirect evidence suggested that the origin of SIV/Delta in the rhesus, a pri- mate of Asian origin, was an African primate, the sooty mangabey monkey, which may harbor this virus asymptomatically. More recently, we have examined SIV/Delta-related pathogenesis of 33 vitro propagated virus isolated from several rhesus with SAIDS and one asymptomatic mangabey. SIV/Delta isolated from a healthy sooty mangabey monkey is as patho— genic in rhesus monkeys as are SIV/Delta rhesus isolates. Death due to SAIDS, evidenced by lymphocyte subset alterations, abnormal immune responsiveness, op- portunistic infection, and lymphoma in one animal, usually occurs in infected animals within 2—12 months post-inoculation, regardless of the source of virus. Several rhesus isolates are pathogenic; one isolate is singularly neurovirulent Of 8 animals inoculated with the neurovirulent isolate, 4 have died with symp— toms of SAIDS; in addition, all had retroviral encephalitis evidenced by numer- ous syncytial cells in brain tissue. Long-term 33 vitro propagation of SIV/ Delta may result in a loss of pathogenicity. Virulence may be re-established, however, by passage of the attenuated Virus from an infected healthy rhesus monkey to a second animal. A comparison of the genetic and antigenic composi- tion of these isolates will provide invaluable information on viral factors re— sponsible for pathogenesis and neurovirulence. WR20 Packaging defective mutants of HTLV-III/HIV AMANDA FISHER, C. Guo, B.R. Starcich, R.C. Gallo & F. Wong—Staal . Laboratory of Tumor cell Biology, National Cancer Institute, NIH, Bethesda MD 20205, USA. Although much is known about HTLV-III replication and the processing of structural components (gag, pol and env) in infected cells, the precise mech- anism by wnich genomic viral RNA is preferentially packaged into virion par- ticles is not known. Studies in avian and murine retroviral systems have suggested that (i) virus particle formation can occur in the absence of genomic RNA and (ii) that sequences intervening the 5'LTR and gag gene are crucial for virus specific packaging. To see whether analogous sequences in HTLV-III/HIV are important in selective packaging of HTLV-III genomic RNA and hence enable the construction of empty (non viral RNA containing) particles, we produced a series of mutants of the biologically active molecular clone pHXBZ-NHTLV-IIIB). These mutants were deleted of 10 to 50 base pairs in the region bordering the 5'LTR and gag. Four such clones were studied in detail and shown to generate viral proteins and viral particles (morphologically indistinguishable from wild type) upon transfection into cos-1 cells. In contrast to the wild type virus, virus generated from the mutant clones was either poorly infectious (3 clones) or resistant to transmission (1 clone) when co-cultured with lymphoid cells. Furthermore, preliminary analysis of the virus derived from the mutants indi- cate unusually low levels of viral RNA. These data hint that the mutants are defective in their ability torecognise and efficiently package viral RNA. In order to unequivocally define the status of our candidate 'packaging mutants' we have constructed a series of cell lines which stably express high levels of of mutant virus. A detailed analysis of these cell lines will be presented. w221 Comparative Sensitivity of Tests for Detection of HIV Infected Cells. A.J. BODNER, A.J. CORRIGAN, M.M. MANAK, G. KELLER, L.L. SIMEK AND R.G.Y. TING, Biotech Research Laboratories, lnc., Rockville, MD. HI! infectivity assays such as virus neutralization determinations require that sensitive methods be used for detection of infected cells so that infec- tion can be detected as early as possible. We have developed two sensitive tests for detection of infected cells, an immunocytochemical slide test using APAAP methods (alkaline phosphatase anti alkaline phosphatase) and an ELISA p24 capture assay. These two tests were compared for sensitivity with two other methods for detgfiting infected cells, reverse transcriptase (RT) assays and hybridization of P labeled core protein DNA probes with disrupted cells. The test samples were cultures of HTLV-IIIB infected H9 cells which ad been serially diluted with H9 cells so that the cultures all contained 10 cells/ml but various concentrations of infected cells. The cells were washed prior to being serially diluted and were then cultured for 14 hours before being tested. The lowest concentration of infected cells which the various tests could detect were as follows: the APAAP slide test, 0.012; the capture test, 0.022 on pelleted cells and 0.22 on supernatant; the DNA probe hybridization test, 0.152; the RT assay, 1.5%. The APAAP slide test and the capture assay were also comparable with each other when used over a two week period to detect emergence of infected cells in cultures of peripheral blood lymphocytes which had been infected with three serial 10—fold dilutions of HTLV-IIIB. Since the capture assay is considerably less labor-intensive than the APAAP slide test but has comparable sensitivity, the capture assay is the better method for many types of infectivity assays. The APAAP slide test. however, has proven to be very effective for detecting HI! antigen presence in sections of tissues such as brain and lymph nodes. WEDNESDAY, JUNE 3 WRZZ Use of Hapten Labeled DNA Probes for the Detection of HIV Sequences in Infected Cells. M. MANAK, G. KELLER, C. CUMMING, M. BOCKELMAN AND B. SISSON. Biotech Research Laboratories, Inc., Rockville, MD. A hapten labeled DNA probe has been developed for the detection of HIV RNA in infected cells. A part of the HIV genome which includes sequences coding for the gag region of the virus were subcloned into a pBR322 vector, and the purified plasmid DNA was chemically labeled with dinitrobenzene. This probe was used to detect HIV sequences in infected H9 cells. Serial dilutions of in ected cells were mixed with uninfected cells, and the RNA from a total of 10 cells was extracted with phenol and ethanol precipitated. The RNA was slot blotted onto nitrocellulose membranes using the slot blot apparatus of Schleicher and Schuell. The filters were baked and hybridized with the hapten labeled probe. Specific hybridization was visualized by reactivity with rabbit anti-hapten antibody followed by an alkaline phosphatase conjugated goat anti-rabbit IgG, and color development. The sensitivity of detection is 1 pg ested on dilutions of plasmid DNA and was similar to that observed with a P labeled probe and autoradiography Virus nucleic aci sequences can be detected in extracts of as little as 10 infected cells (10 viral genome equivalents). For even greater sensitivity, the probe can be used to detect viral sequences in individual infected cells by in situ hybridization. Cells were fixed on microscope slides with AZ Paraformaldehyde and stored in 702 ethanol until tested. Following a 3 hour hybridization, infected cells were visualized by the double antibody system described above. Using this method, individual infected cells can be detected in a vast excess of uninfected cells. WR23 Incidence of Seronegativity to _H_|_V and HTLV-l in individuals infected with either virus. BERNARD J. POIESZ*. G. EHRLICH", L. PAPSIDERO“, R. MONTAGNA**, S. KWOK , J. SNINSKY***, et.a|., *SUNY Health Science Center and VA Medical Center, Syracuse, NY, “Cellular Products. lnc., Buffalo, NY, ***Cetus Corporation, Emeryville, CA One thousand AIDS/ARC patients and 120 adult T-cell leukemia or HTLV-I carriers were prospectively tested for antibodies to HIV or HTLV-l, re- spectively in an ELISA assay. One of 1000 AIDS/ARC patients (0.1%) were seronegative for anti-HIV antibodies and 1 of 120 HTLV-I infected patients (0.8%) were seronegative for anti-HTLV-l antibodies. Seronegativity was confirmed by Western blot and radioimmunoprecipitation assays and was re- peatedly negative in several samples obtained over one year's time. HIV or HTLV-I infection was confirmed by detection of viral proteins by immuno- peroxidase staining of infected tissue with antiviral monoclonal antibodies and by detection of viral nucleic acids via enzmatic amplification and oligomer restriction detection techniques. Hence, seronegativity to these 2 viruses occurs with a finite, but real, frequency. Enzymatic in vitro gene amplification identified both seronegative individuals and represents a sensitive and specific method to confirm the diagnosis of HIV and HTLV-I infection. WP.24 Genetic Characterization of Biologically Different HIV- Variants H. RUBSAIEN-NAIGMANN", H. VON BRIESEN‘, L. BIESERT”, K. HENCO", H.D. BREDE" *Georg-Speyer-Haus, Frankfurt, FRG, **DIAGEN GmbH, Ddsseldorf, FRG Human immunodeficiency virus (HIV) was cultured from either peripheral blood lymphocytes (PBL) or in some cases from cerebrospinal fluid (CSF). Cultures for virus isolation were performed from more than 180 geman AIDS. ARC, LAS and virus exposed asymptomatic patients. These isolates differed remarkably in their biological properties (cytopathic effect on lymphocytes and replication rate). In the majority of AIDS-patient with neurological symptoms well-growing strains were obtained from PBL, whereas all but 2 isolates from CSF of the same patients grew slow and to only low titres on PBL. One isolate from PBL was molecularyly cloned. Restriction analysis and nucleotide sequencing of several of the clones revealed the simultaneous existence of at least 4 distinct HIV variants in the peripheral blood of the patient. The amino acid sequence divergence of the variants from LAV/HTLV IIIB in the env/lor region was about ID! with multiple insertions and deletions. .Hhile the isolate from the patient's periphery grew readyly and with the formation of big syncytia on PBL, the virus from his CSF grew badly and with only marginal CPE. The genetic characterization of this slowly growing strain is in progress. HERBERT KUHNEL‘, 114 WP.25 Localization of the Transmembrane Anchor Domain of the Envelope Glycoprotein, gp160, of Human Immunodeficiency Virus PHILLIP w. BERMAN*, w. MUNES, 0. HAFFAR, Genentech, Inc., 50. San Francisco, CA, USA. In order to understand the mechanism of HIV—1 infection, it is important to determine which domains of the HIV envelope glycoprotein are exposed on the surface of the virus. While there is general agreement that gp4l is an integral membrane protein, its orientation in the membrane, and the number of times it spans the viral envelope have yet to be determined. Hydropathic analysis of gp160 revealed two potential transmembrane biding domains, both occurring in gp4l (residues 5l2—54l, and residues 684-707). We have attempted to identify the membrane anchor region by construction of a series of mutant gp160 genes with truncations or deletions occurring in the gp4l region. Transfection of thee variants into mammalian cells demonstrated that mutations that preserved the first hydrophobic domain in gp4l and deleted the second hydrophobic domain encoded proteins that were secreted from the cells.. These results demonstrate that the first hydrophobic domain of gpAl is not sufficient for membrane biding and suggest that the carboxyterminal 174 amino acids of gplGO contains the membrane anchor sequence. Although it is possible that the two hydrophobic domains in gp41 interact to fonn a membrane binding domain, the simplest model would suggest that the entire gplGO molecule, with the exception of the last I74 residues is exposed on the viral surface. Serodiagnosis of HIV- -infections by an Oli90peptide WP26 ELISA KARL-OTTO HABERMEHL,B.ZORR,H.HAMPL,H.ZEICHHARDT,P.NILLINGMANN, ns .0 1n.an xper.Virology, Free University of Berlin, Hindenburgdamm 27, 1000 Berlin 45, Germany The ELISA has been proven as a highly sensitive and specific method in HIV-diagnosis. Nevertheless, unspecific reactions resulting in false positive results occur due to impurities of the antigen preparations. This problem can be solved in principle by using defined synthetic oligopeptides representing well conserved epitopes from different structural proteins of HIV-1. A number of synthetic oligopeptides (synthesized by Dr.Frenzel, Biochrom) have been screened in different ELISAs for reactivity against HIV-positive sera or negative controls (blood donors or patients from routine virus-diagnostic). Four oligopeptides containing Zl aminoacids each representing different epitopes from the proteins p18, p24, gp4l or gplZO with an optimal serologic specifity were selected and combined as a mixture in an ELISA. It could be demonstrated that with 505 blot-confirmed HIV- positive sera a reactivity of 100 % could be obtained. 2729 out of 2735 negative sera were in this ELISA non-reactive, indicating a specificity of 99,8 1. The good specificity and sensitivity was underlined by a significant difference between the extinctions of the non-reactives and the reactives in so far as 97 % of the positive probes showed an extinction of > 1.95 and 99,3 % of the negatives an extinction of ( 0.l5. WEZ7 HIV antigenemia in patients with AIDS or related disorders : a study in European and Central African populations. F. BARIN‘, A.BAILLOU*, E. PETAT', G. GUEROIS". P. CHWTET‘“. A. GOUDEAU' et al., 'lab. Virologie, CHRU Bretonneau. Tours. France, "lab. llématologle, CHRlJ Trousseau, Tours. '**Dept Medecine Interne. CHRU Bretonneau, Tours. The presence of human immunodeficiency virus antigen (5) (HIV-Ag) was analysed in the serum of AIDS patients. ARC patients and symptamless seropositlve people using a solid-phase sandwich- type ELISA (Abbott, Abbott Park. 1].). Individuals entering the study were either French (group I) - or Central African residents (group 2). GROUP I (Nb : 80) HIV Ag was detected in 48 1 (IO/21) of AIDS patients. 22 1 (5/23) of ARC patients, and 3 1 (1/36) of symptomless seropositive Individuals. HIV antigenemia was correlated with the absence of antibody to HIV m antigens with a competitive antibody lmunoassay employing hlV core antigens produced by recombinant DNA technology (ENVACORER. Abbott). Fifteen out of 27 anti-gig negative individuals (56 S) were HIV-Ag positive against only I out of 53 anti-35g positive individuals (2 Z : p<10‘7). Longitudinal studies showed that HIV-Ag was transient in primary HIV infection. 0n the contrary, late appearence of HIV-Ag in seropositive individuals was associated with persistent antigenemia and seemed to correlate with clinical deterioration. GROUP 2 (Nb : 144) Only I out of 55 AIDS patients (2 1) was HIV Ag positive. None of 52 ARC patients and 37 symptomless seropositive Individuals presented HIV antigenemia. In contrast with European AIDS patients. 95 S of AIDS patients (55/58) from Central Africa were positive for antibody to HIV core antigens. This study shows that expression of HIV-Ag in disappearance of antibody to ggg antigens. The clinical value of HIV antigenenia that may exist for seropositive European individuals cannot be applied to Central African seropositive populations. This observation has practical and fundamental implications that will be discussed. serum is correlated with absence or WEDNESDAY, JUNE 3 wnzs Expression of a Functional Protein from a Chemically Synthesized Gene. E.R. HENDRICKSON, B.Q.FERGUSON. L.S. STREHL. L.T. BACHELER. DJ. COX AND S.R. PEITEWAY, E. l. Du Pont de Nemours. Medical Products Department. Wilmington, DE. The predicted 26I base pair coding sequence of HIV-lllB tit-Ill has been chemically synthesized. cloned in l_5. Eli and expressed in HeLa cells. The Lat-ill sequence was fused to a translational start signal and placed under SV40 early transcriptional control. Co-transfection of the synthetic Lat-Ill gene along with a reporter gene (chloramphenicol acetyl tranferase or s-galactosidase) linked to an HlV LTR confirmed that the synthetic gene product exhibits similar activity to Lat-Ill expressed from HIV genomic DNA in the trans-activation of the LTR. In the design of the synthetic coding sequence, unique restriction sites that do not change the primary amino acid sequence were introduced to facilitate assembly of the gene. These restriction sites can be used to easily replace segments of the gene with synthetic oligonucleotides containing any desired sequence changes (cassette mutagenesis). This approach is being used to analyze structural changes and their effect on the function of the tat-Ill gene product. HIV guru WP.29 Neurological AIDS: Isolation and characterization of noncytocidal natural variants of human immunodeficiency virus (HIV) from AIDS patients with neurological disorders RITA ANAND‘, J. MO0RE*, T. CHEUNG**, F. SIEGEL***, S. FORLENZA**** and C. REED*. *Centers for Disease Control, Atlanta, Gs., **Coler Memorial Hospital, Long Island, New York, ***Long Island Jewish Hospital, Long Island, New York, ****Nassau County Medical Center, East Meadow, New York. Heterogeneity in AIDS virus isolates has been well documented but has not been correlated with the clinical manifestations of AIDS or with the functional biology of the virus. The occurence of central nervous system involvement in certain AIDS patients with minimal neurohistopathology pronpted us to isolate viruses from such patients and delineate their cytopathic properties. Five virus isolates, termed NAl-NAS, were obtained from four neuro-AIDS (NA) patients. The isolates were identified as HIV by antigenic cross-reactivity and nucleic acid hybridization to HIV-specific antibodies and DNA probes. The replication and cytopathic properties of these isolates were studied and compared with lymphadenopathy-associated virus (LAV) in vitro. All NA isolates exhibited replication efficiency equivalent t;_lAV, but four of five isolates did not kill T4 cells. The frequency of Té-positive cells in LAV-infected cultures (normal adult peripheral blood lymphocytes) decreased to 1.62 in 15 days, but the frequency of TA-positive cells in uninfected cultures and in cultures infected with noncytocidal variants remained between 462 and 64%. These findings provide evidence for the existence of noncytocidal natural variants of HIV, and raise the possibility that in some AIDS patients neurologic disorders might be caused by HIV variants that are noncytocidal to T4 cells. VVR30 A simple and economical HTLV-III TEST for underdevelop countries. AUGUSTA K.TAKEDA;OCUNO L.; TATUTA C.; Prods.Biol. Sao Paulo - Brasil. Present HTLV-III tests require the use of equipment and techni— cal skills not readily available in underdeveloped countries. In addition the cost per test make it impossible for these countries to establish a policy of individual testing for all blood donors. This has resulted in the practice of blood pooling in order to re- duce cost.To overcome these problems,PASSIVE HEMAGGLUTINATION TEST (PHT) has been established.This test involve the fixed red cells sesitized with HTLV—III antigen. 25ul of sera samples of each do — nor is mixed in 25u1 of phosphate buffer saline .lSM pH 7.2 and adding 25ul of sensitized red cells.After 15min PHT become positi— ve if agglutination patterns can be seen,and negative when cells do not agglutinate and form a well defined button.The specificity and sensitivity is exactly the same compared with ELISA.In regar— ding to reproductivity and stability is far better then ELISA when it was compared with 1000 acre samples of blood donnors,suspected and AIDS cases.All positive samples in any methods were confirmed by WESTERN BLOT.In conclusion the PHT is very easy to be done, to be read does not require the use of equipment or a trained techni— cian~,and it is very fast;15min compared to l20min.The cost is only 1/20 of current methods,before adding the cost of equipment. OUTUKI N.K.; Salck Ind.Com. 115 WP31 Transmission of Human Immunodeficiency Virus to Non-hematopoietic Cells by Co—cultivation. HIROO HOSHINO, YASUHIRO TAKEUCHI, Gunilla University School of Medicine, Maebashi, Gunma, Japan Infection with human immunodeficiency virus (HIV) often induces neurological disorders. We examined susceptibilities of non- hematopoietic cell lines to HIV. HIV produced by H9/HTLV-IIIB cells, kindly supplied by Dr. R. C. Gallo, was mainly used. NP-l, NP—2, 0—251 MG and HOS human cells and S*L'CCC cat cells were co— cultivated with lethally irradiated HIV-producing Molt-4 cells. The former three cell lines had been derived from human gliomas. Only NP-1 cells (OJ—0.5%) became immunofluorescent on indirect immunofluorescence assay. Sera of seropositive hemophiliacs inhibited the transmission. 0-251 MG cells were not susceptible to HIV, although these cells expressed glial fibrillary acidic protein which is known to be specifically detected in glial cells. On the other hand, 1-43% of NP—l, NP—Z, U—251 MG, HOS or S‘L‘CCC cells became immunofluorescent after co—cultivation with T cells doubly infected with HTLV-‘l and HIV. Thus, HIV was transmitted efficiently to non-hematopoietic cells in the pre- sence of HTLV—l. Sera from ATL patients inhibited the trans- mission. HIV antigen-positive NP-l and NP-2 cells were cloned. Each clone contained 1 or 2 copies of HIV genomes. some clone produced infectious HIV abundantly, while some clone produced non—infectious HIV. Some clone contained defective HIV. The procedures described here may be useful for elucidation of bio— logical and pathogenic properties of HIV. WP32 HIV-related viruses in pregnant women in Gabon. ERIC DELAPORTE‘, M.C.DAZZA”, S.WAlN—HOBSON”‘, F.BRUN- VEZINET”, B.LAROUZE““, A.G.SAlMOT“"', et al. CIRMF (Gabon)‘, Laboratoire de virologie, hopital Claude Bernard“; Unité de Biologie Moléculaire et d'immunologie des retroviruses, Institut Pasteur‘”, lMET/lNSERM U13”", Hopltal Claude Bernard - Paris - France. During a study of vertical transmission of retroviruses in Gabon (Nov.'85 to Nov.‘86), serum samples from 750 women were collected each 3 months during and after pregnancy. Twenty-four sera were found HlV-1 positive by Elisa (Elavia). By HIV—1 Western blot (WB)(LAV-B|ot), one serum was negative and 2 were confirmed as HIV-1 positive. Twenty—one sera did not fit the criteria for HIV—1 positivity but exhibited the p25 band associated to the p55 or to another band of about 37 kD (14 cases). The same banding pattern was found in all serial samples from each woman. All these 21 sera were HIV-1 negative by RIPA. By LAV-2/HlV—2 Elisa all 21 sera were negative and by HIV—2 WB all presented the p26, with no antibodies to the envelope glycoproteins. We performed retrovirus isolation from peripheral blood lymphocytes from 2 of these 21 women. In the two cultures a reverse transcriptase activity (RTa)was detected at day 21 la the cell—free supernatants. The RTa persisted at the same level (50x10 - 90x10 rpm/ml), without peak and with no obvious cytopathic effect on the infected T—lymphocytes. No decline of the lymphocyte proliferation was observed. The cell—free supernatants reacted with HIV-1 polyclonal antibody by an antigen capture essay. By an indirect IF assay the cultured infected T-lymphocytes from the 2 women reacted obviously with the sera of each patient and weakly with human HIV-1 antibodies. No reaction was observed with HTLV-l nor HIV-2 antibodies. Southern Blot analysis showed a weak hybridization with the entire HIV—1 genome in conditions of high stringency. In January 1987, all these women were healthy and their total lymphocytes count was normal. WP33 HIV Neutralizing Antibodies to a Recombinant Segment of the Virus Envelope: Studies with Multiple Virus Variants and Neutralizing Epitope Definition JAMES R. RUSCHE", D. LYNN*, R. GRIMAILA*, T. MEWS**, M. W***, S. PU'I‘NEIY‘, et al.,*Fepligen Corporation, One Kendall Square, Building 700, Cambridge, MA, MDepartment: of Surgery, Duke University Medical School, Durham, NC, ***I.aboratory of Tunor Cell Biology, National Cancer Institute, National Institute of Health, Bethesda, MD. PBl, an E. coli produced segment from the carboxyl—terminal half of the gp120 envelope protein, elicits antibodies that neutralize HIV infection in vitro (Science, fl, 1392—1395, (1986)). This neutralization is HIV strain specific. We have produced the same region from four other HIV isolates and used these as immmogens individually and in combinations to determine the virus neutraliza- tion patterns and to achieve an immirngen capable of eliciting broadly neutrali— zing antibodies. In addition, we have obtained fragments of PBl by genetic and proteolytic rreans to define n‘ore precisely the epitope that elicits the neutralizing response. These have been used as immmogens and in conpetition binding experiments with neutralizing sera. Implications of the results of these approaches for the development: of an effective vaccine against AIDS will be discussed. WEDNESDAY, JUNE 3 WR34 Molecular Characterization of the Type D Retroviruses in Macaques LESLEY M. HALLICK*, ILK. AXTHELM“, R.A. KARTY", B.J. WILSON“, S.M. SHIIGI**, AND W.P. MCNULTY**, *Oregon Health Sciences University and **Oregon Regional Primate Research Center, Portland, OR. A series of related, but genetically distinct type D retroviruses has been isolated from Asian macaques suffering from simian AIDS (SAIDS). Two serotypic groups are recognized: SRV I, originally isolated from the California and New England PRCs and most closely related to Mason—Pfizer monkey virus; and SRV 11, isolated from the Oregon and Washington RPRCs and associated with the Kaposi's sarcoma—like neoplasm, retroperitoneal fibromatosis (RF). The SRV II strain (lIC) isolated from M. nigra with a high incidence of SAIDS/RF at the ORPRC has been cloned in collaboration with the CAPRC, and used to screen other macaque species at the ORPRC. Currently 52 of the rhesus colony (M. mulatta) are virus-infected, and an additional 251 have evidence of prior infection. The rhesus isolate (SRV IIR) is serologically indistinguishable but genetically distinct from SRV IIC, and is associated with a lower mortality rate. A severe form of SAIDS has also been observed in the Japanese macaque (M. fuscata) troop at the ORPRC. Restriction maps of isolates from affected animals are identical to SRV IIR. In contrast to our experience with M. mulatta, SRV IIR infection appears to result in clinical SAIDS and death in a high percentage of M. fuscata. Two SRV IIR isolates, one from a Japanese and one from a rhesus macaque, exhibit a slightly altered restriction pattern. These two variants appear to be identical to one another. Recently, two M. mulatta imported from the People's Republic of China have been shown to be actively infected with a new type D SRV more closely related to SRV I than to SRV II. Investigations are underway to determine whether this strain constitutes a third serotype. WP35 Expression and Analysis of HIV gPlZO Analogues Secreted from ' Saccharamyces Cerevisiae DONALD J. DOWBENKO*, M. RENZ*, C.Y. CHEN*, R.A. HITZEMAN*. So. San Francisco, CA, USA. Yeast cells have been engineered to produce a secreted form of the HIV envelope glycoprotein (gPIZO). The 500 amino—acid coding region of the gPlZO envelope gene was fused to the human serum albumin signal sequence and programmed for expression with the yeast chelatin promoter. The resulting plasmid was transformed into a wild type yeast strain (ZOE—12) or into a yeast mnn9 manno protein mutant (Tsai gt 31., J.B.C., 259, p. 3805, 1984). Proteins secreted from cells in the presence of copper were analyzed by immunoblotting and shown to react with several HIV gPlZO—positive human and rabbit sera. Secreted protein from wild type 208-12 cells migrated as a 3300 kd polypeptide smear on low percentage gels presumably due to hyperglycosylation of the envelope protein. However, protein from the supernatant of mnn9 cells migrated as a diffuse band at ~130 kd. In both cell lines, the secreted envelope glycoproteins were sensitive to N—glycanase treatment; however, only the 130 kd mnn9 protein bound to an immunoaffinity column containing human anti—HIV IgG. Rabbit sera directed against purified mnn9—gP130 reacted with native gPIZO from HIV infected cells. Genentech, Inc . , WP36 Identification of gag—epitopes by a panel of MAb in a serie of HIV ' isolates IRENE N. WINKEL, M. TERSHETTE, P. MIEDEMA, J.G. HUISMAN Central Laboratory of the Netherlands Red Cross Blood Transfusion Service, incorporating the Laboratory of Experimental and Clinical Immunology of the University of Amsterdam, Amsterdam, The Netherlands Immunization of Balb/c mice with TX-lOO disrupted sucrose gradient purified HIV enabled a panel of 10 monoclonals against HIV-gag products to be produced. Characterization by immunoblotting and radioimmunoprecipitation assay using 125I-labeled HIV-proteins together identified 8 hybridomas which were reacting variously with gag-proteins pr55 and p24 and 2 hybridomas reacting with pr55 and p13. In order to characterize the different anti—gag clones a cross-competition RIA was developed. Purified IgG from each of the clones was labeled with 1251 and each clone allowed to compete with itself and all other clones as radiolabels for HIV antigens bound to sepharose beads. It was concluded that these monoclonals react with presumably 6 different gag-epitopes. Three of these were mapped on tryptic peptides. Different combinations of antibodies were used to detect the presence of HIV-gag products in various isolates by a p24 capture assay. CLB—Zl as catching antibody and 125I—CLB—l4 as tagging antibody appeared to be the most broadly reactive of all antibodies. Screening of 70 HIV isolates positive in this capture assay, two isolates failed to react with CLB—47. This was not due to a low level of HIV expression since elevated levels of RT activity were observed. To explain this lack of reactivity, a genetic variation or post-translational modification of the anti-gag epitope might have occurred. 116 St BRUNO SPIRE*. WE37 Molecular Cloning and Nucleotide Sequence of a Highly Cytopathic rain of Human Immunodeficiency Virus. v. ZACHAR**, F. BARRE-SINOUSSI*, F. GALIBERT***, J.C.CHERMANN* an . E***,*Institut Pasteur, Viral Oncology Unit, Paris, France, ** Institute of Virology SAV, Bratislava, Czechoslovakia, *** Hépital Saint- Louis, Laboratoire d'Hématologle Expérimentale, Centre Hayem, Paris. France. A highly cytopathic variant of the human immunodeficiency virus type 1/ HIV1/ was isolated from a zairlan patient with AIDS. When biologically tested on MT4 cells, a striking cytopathic effect, estimated to surpass at least one thousand times that of HIV 1 prototype was disclosed. Preliminary experiments suggested that this variant possesses a completely different restriction en- zyme pattern in Southern blot analysis. In order to determine the putative genomic regions involved in observed biological features, a molecular cloning of this isolate proviral genome was accomplished. The genomic library was pre- pared from partially digested DNA of persistently infected CEM cell line and established by means of EMBL 3 vector. Recombinants were obtained on succes- sive screening employing HIV 1 probes. The nucleotide sequence and resulting implications which will be presented might inform on the cytopathogenicity of AIDS viruses. WR38 Reactivation of Human Immunodeficiency Virus Long Terminal Repeats by Herpesvirus Infection *. D.P. BEDNARIKII, N.B.K. RAH. W.A. HASELTINE", 6.3. HAYWARDll and P. M. PITHA". *The Johns Hopkins Univ. School of Medicine: Baltimore. MD. **Dana—Farber Cancer Institute: Boston. MA We have shown recently that the expression of chloramphenicol acetyl- transferass (CAT) directed by human inmunodeficiency virus (HIV) long terminal repeat (LTR) 1n stably transfected cell lines can be activated both by HSVrI infection (Mosca, at al.. Nature 325:67—70, 1987) and S-azacytidine treatment (Bednarik. et al.. J. Virol.. In Press). Both HSV. infection and 5-azacytidine treatment led to an increase in CAT activity, accumulation of CAT mRNA and an increase in CAT gene transcription. suggesting that the activation occurs at the transcriptional level. The HSV gene product responsible for HIV LTR activation was identified using HSV-I ts mutants and the cloned HSV-I imediatrearly genes for IE175K, IE110K proteins and the late structural protein Vnw65. The inducible region within the HIV LTR was identified using the Bal 31 deletions in the 5' region of HIV LTR. When a 71 nucleotide long fragment from HIV LTR was placed in front of a heterologous. non-inducible gene (mur'lne d-39/+22 CAT), the expression of a-CAT gene was induced by HSV infection. The HIV LTR can also be induced by cytomegalovirus (CMV) infection; however. the results suggest that the activation by CNN does not occur through the same sequences that are recognized by the HSV factors. In addition to HSV-I induced activation. the effect of the HIV: coded transactivation TAT protein on the HIV LTR was also investigated. WP39 Expression of Envelope Glycoproteins of Hman Immunodeficiency ' Virus by an Insect Virus Vector SHIU—DOK Hu, 5. KOSONSKI, K. SCHAAF; Oncogen and Genetic Systems Corporation; 3555 First Avenue, Seattle, WA 98121 The envelope gene of human immunodeficiency virus (HIV) has been inserted into the genome of an insect virus vector (Auto ra ha califomica nuclear polyhedrosis virus). Upon infection of tissue culture cells, this recombinant virus produced a 150k lnmmoreactive polypeptide related to the precursor envelope glycoprotein (gp150) of HIV. Radioisotope labeling with H—mannose indicated that this recombinant-made polypeptide was glycosylated. Forty—eight hours after infection, immnoreactive proteins of molecular weights 120—130k and 41k were also detected. By their reactivity to monoclonal antibodies, these proteins were identified as analogs of mature envelope glycoproteins gp110 and gp41, respectively. To demonstrate the potential usefulness of these recombinant—made proteins in diagnostic tests for AIDS, we used infected cell lysates as antigens in a solid—phase immunoassay to screen a panel of 48 human sera. Results of this inmunoassay correctly identified all positive and negative samples previously classified by Western blot and inmmoassays based on disrupted virions. A relatively low cutoff value (OD-0.18) and a high signal-to—background ratio (average )9) were obtained using crude infected cell lysate without prior purification. Studies are also in progress to determine the lurmmogenic properties of the envelope glycoprotein analogs produced by insect virus vectors. WEDNESDAY, JUNE 3 wp4o Heterosexual Transmission Study in Infected Intravenous Drug ' Abusers J.R. ROBERTSON, CAROL A. SKIDMORE, L. ADAMS, L. MCDONALD, M.M. MORRISON, B.V. KUENSSBERG, Edinburgh Drug Addiction Study, Edinburgh, Scotland In a cohort study of 250 Intravenous drug abusers (IVDA) with a high seroprevalence of antibody to HIV (51% of 16A tested since September I983) 1% couples were identified in which sexual relationship data were available to allow heterosexual transmission studies. Stored serum (for hepatitis testing) allowed accurate identification of seroconversion dates and questionnaire data and the high evidence of pregnancy (6) confirmed the absence of barrier contraception during the study period. The study group therefore was of 11 (92%) male and I (8%) female seroposltives. When tested 2 (16%) of the female partners were found positive and the single male exposed sexually to HIV was negative. The average length of exposure to HIV was 19.1 months in the whole group (19.2 in the non-converters and I8.5 months in those found to have transmitted the infection). If the negative status indeed Indicates non infection then It seems likely that transmission may not now take place. The couples who had transmitted the virus were all positive at first testing and subsequent testing in the remaining couples has revealed no new seroconversions even in the continued absence of appropriate barrier contraception In most cases. The problem of early transmission followed by apparent reduced infectiousness is similar to that seen amongst those continuing to share infected needles and syringes in Edinburgh. WP41 HIV Seroconversion In Intravenous Drug Abusers: Rate and Risk Factors ' ELLIE E. SCHOENBAUM*, PA SELWYN*, D HARTEL*, RS KLEIN*, K DAVENNY*, GH FRIEDLAND*, et a1, *Montefiore Med. Ctr., *Albert Einstein College of Medicine, Bronx, NY and CDC, Atlanta, Georgia, USA. We are studying the rate of and risk factors associated with HIV seroconver— sion in intravenous drUg abusers attendingaNYC methadone program. From July 1985- April 1986 subjects were enrolled in a prospective study of the natural history of HIV infection. Standardized interviews eliciting demographic data, drug use, sexual and medical histories and physical examinations were performed. Blood for serum antibodies to HIV was obtained. Among 498 enrolled initially, 329 (662) were seronegative (SN) and 169 (34%) seropositive (SP). During 16 mos. of follow-up, 142 (98 SN and 44 SP)had repeat HIV antibody determination. Nineteen of 98 original SN (19%) acquired HIV anti— body after a mean 11 mos. of follow—up (range 4-16 mos.). Interview data for the follow-up period are available for 128/142 (90%) ofre- tested subjects, (92 SN, 36 SP) In this subgroup, 77of 92originalSNs(84Z) re— mained SN and 15 of 92 (16%) developed HIV antibody. All 36 SPs remained SP. Among demographic variables, non-white race, but not age or gender, was associ- ated with seroconversion. Non-whites comprised 13/15 (87Z) of seroconvertersand 33/77 (432) SN5 (p(.01). 0f the drug variables, seroconversion was associated with reported intravenous drug use during the follow—up period (p(.01), mean number of days per month using IV drugs (p(.01), use of 'speedball"(heroin and cocaine mixed) (p(.03), but not heroin or cocaine alone. of those injecting drugs, 11/15 (732) of seroconverters reported sharing needles vs. 22/36 (61%) of SNs (p).05). History of sex with another intravenous drug abuser was associ— ated with seroconversion (p<.01). No seroconverters reported sex with prostitutes. Male homosexual activity was reported by one seroconverter and one SN only. These preliminary data suggest that both intravenous drug use and sexual ac— tivity put heterosexual intravenous dru abusers at increased risk for HIV infection. SN intravenous drug abusers in a methadone program remainat highrisk r deve o t f HIV t b di 19% t f 11 — f 11 . 1 r5 {I‘igh rislli gginalcand drag begav53r(continu2?an o ow Up 0 mos ) as ong 1 WP42 Seasonal Variation in AIDS and Opportunistic Diseases ' THOMAS A. PETERMAN, R.H. BYERS, AIDS Program, Center for Infectious Diseases, Centers for Disease Control, Atlanta, CA. We looked for seasonal variation in the diagnosis of AIDS, and in the diagnosis of opportunistic diseases seen in AIDS patients. Seasonal variation in AIDS or in the initial opportunistic disease would suggest that an agent with a seasonal variation acts as a cofactor for the development of AIDS. Seasonal variation in subsequent opportunistic diseases could reflect the'epidemiology of that disease in an already immunosuppressed population. We studied the number of diagnoses per month for U.S. AIDS cases during the 72 months from January 1980 through December 1985. The upward-trend in diagnoses per month was adjusted for by linear regression, 3 von Hann filter was used to smooth the curve, and Roger's test for seasonality was applied. We observed small but statistically significant seasonality for the diagnosis of AIDS (121 difference, peak—-summer, trough-—winter, p<0.00005). For 9 initial manifestations of AIDS, we saw statistically significant seasonality only for Pneumocystis carinii pneumonia (14% difference, peak--summer, trough--winter, p<0.005) and Kaposi's sarcoma (15% difference, peak--summer, trough-—winter, p<0.005). For 9 subsequent diagnoses, seasonal variation was seen only for cytomegalovirus infection (CMV) (34% difference, peak--spring, trough-—fall, p(0.05). (Although not statistically significant, we noted a similar distribution for CMV as the initial manifestation of AIDS.) Primary lymphoma of the brain showed some seasonality both as the initial and as a subsequent diagnosis: when combined, this was a statistically significant difference (44% difference, peak—-summer, trough--spring, p<0.05). We conclude that there is no important seasonality in the onset of AIDS, but there may be some seasonality to CMV and primary lymphoma of the brain in immunocompromised patients. 117 WE43 Stability of HIV Infection Prevalence Over 10 Years in a Rural Population of Zaire. KEVIN EL 2; COCKI N. NZILAMBI, D. FORTHAL, R. RYDER, P. PIOT, J.B. MCCORMICK, et.al Division of Viral Diseases, Centers for Disease Control, Atlanta, GA, U.S.A.; Project SIDA, Kinshasa, Zaire; Institute of Tropical Medicine, Antwerp, Belgium. Five (0.8%) of 659 human serum specimens collected in the Equateur Province of Zaire in 1976 following an epidemic of Ebola hemorrhagic fever contained antibody to human immunodeficiency virus (HIV). Eighty-six previously seronegative persons were traced in 1985/1986 and were found to remain seronegative. A serosurvey in 1986 using a cluster sampling technique in the same communities showed a prevalence of HIV antibody of 0.81 in 389 healthy adult villagers sampled. In 136 pregnant women the seroprevalence rate was 2% and in 283 prostitutes 11%. Patients with AIDS were observed in hospitals in different parts of the Province. Their risk factors were increased numbers of sexual partners and residence outside of the area. HIV infection rates have not changed over 10 years and remain low in rural Equatorial Zaire, but risk groups have been identified. These findings suggest that social factors associated with urbanization are important in the rapid spread of AIDS in Africa. WP'44 Field Assessment of an Enzyme Inmunosorbent Assay for HIV Antigen (HIV Ag) SALLY HOJVAT, M. LEUTHER, M. LOMBARD-CANNAN, E. MORRISEY, (. ) - OMEK, L. VALDIVIA, Abbott Laboratories, Abbott Park, IL 60064 U.S.A Seven sites in N. America and Europe have assessed the reproducibility, sensitivity and specificity of solid phase enzyme Imunosorbent assay (ELISA) to detect HIV Ag. Reproducibility was examined by multiple testing of 4 serial dilutions (89 to 968 pg/ml) of an HIV Ag positive specimen. The coefficient of variability ranged from 846% within and between run. The prevalence of HIV Ag and HIV antibodies, p24 and gp41, as markers of HIV infection was assessed In the following groups of. individuals using specific ELISA's: 326 AIDS, 266 ARC, 436 seropositive asymptomatic subjects, 69 hemophiliacs, 274 seronegative asymptomatic subjects and control groups of 1460 healthy individuals and 345 patients with diseases other than AIDS. No HIV Ag or HIV antibodies to p24 and gp41 were detected 'In either control group or in seronegat'lve asymptomatic Individuals. Antibody to gp4l was a constant marker, present in 99 to IOO‘Z of seroposltive specimens. The level of p24 antibody decreased with the severity of HIV symptoms from 81% in asymptomatic seroposltlves to 61% In ARC and 45% In AIDS patients. The prevalence of HIV Ag In seropositive subjects was 40% in AIDS, 24% in ARC and 7% in asymptomatic subjects. In sumary, HIV infected individuals, demonstrate a direct correlation between Increased antigenemla and the severity of symptoms. This may be predictive of the clinical complications of HIV infection, such as AIDS and ARC. wp45 Future Invasion 01 HIV into a Broader Spectrum of Americans ' Predicted lrom HBV Example. N F ', M. ALTER" enters ,or Iseasa omrol, 'Berkeley, CA and "A’Ilanla, GA . HepaIiIIs B VIrus (HBV) has transmission panerns remarkably Similar to human immunodeficiency vnrus (HIV). As a result, the diseases caused by the two viruses occur In‘populalion subgrou 5 whose behaVIor or medIcaI IherapIes put them at nsk ol Iniecnon, HIV is a recent y imroduced virus which has yet Ioequillbrale In the Amencan populalIon, We have compared Ihe results oi transmISSIon studies of HIV and HBV Io jud e the SImIIamIes ollhese viruses and the usefulness oi HBV as a model to mad the imure 01 HIV disease. ‘ ‘ Overall, the lransmlssion ole and HBV are remaniablrylsimllar. A side-by-SIde companson oi HBV and HIV In homosexual man found H to be about 1/4 as transmissible per exposure SFrancis and Byers). WiIhin this group the high ‘ carner-Io-Inlecllon ram 01 H V has more than made up tor the discrepancy In terms of overall eIIIcacy oi spread. Prevalence and incidence studies 01 heterosexual groups exposed to Inlected male or Iemale anners have shown essentially idemical rates oi Infection Ior lh_e two VIruses. or IV drug users, it Is clear that HIV can saturate the populaIIon In a manner ve similar to HBV. Because 01 the remarkable epidemIoIogIc sImIIamIes 91 IV and HBV, we presume that. I! ‘ Is dog-210 slop unher extenSIon 01 HIV InleclIon, HIV disease ‘ panems WII eventually mirror HBV's. That will mean that about 1/21he cases WIII ave been Iniected through homosexual comact and/or IV drug use and 1/2 the cases will have been Iniecled by enher documented or presumed heterosexualexposure. The demography 01 cases, usmg the HBV predIciIon would change consuderably. Whliles would acooum 10! 67% of cases, blacks 24% and hispanics 8%: 67% would be ma 9. WEDNESDAY, JUNE 3 WP46 Predictors of Survival for AIDS Cases in San Francisco. GEORGE F. LEMP, J.L. BARNHART, G.H. RUTHERFORD, D. HERDEGAR, Department of Public Health, San Francisco, California. We evaluated survival following AIDS diagnosis for 2,489 patients reported in San Francisco between July, 1981 and September 30, 1986. Cases were followed at six month intervals from diagnosis to death. The maximum follow- up time was 70 months (mean = 17.8 months). Follow-up was nearly complete, with only 2 percent of cases known to be lost to follow—up. The median sur- vival for all cases was 11.2 months, with a three year survival rate of 13.1 percent. Median survival varied significantly (p<0.05) with: initial diagnos- tic grouping (Kaposi's sarcoma = 17.3 months; Pneumocystis carinii pneumonia = 10.2 months; Both KS and PCP = 12.3 months; other opportunistic infections = 6.2 months); age at diagnosis (i 19 yrs. 3.2 months; 20-29 yrs. = 12.5months 30 - 39 yrs. = 12.0 months; 40 — 49 yrs. 10.8 months; 50 - 59 yrs. = 8.2 months; 2 60 yrs. = 5.5 months): and risk group (homosexual/bisexual male = 11.2 months; IV drug user = 6.5 months; homosexual/bisexual IV drug user = 10.6 months; all other risk groups = 7.6 months. Median survival did not vary significantly with race, sex, or year of diagnosis. Cox proportional hazards regression analysis indicated that initial diagnostic group, and age at diag- nosis were significant hi<0.05) predictors of survival in a multivariate model, while race, sex, risk category, and year of diagnosis were not. These data suggest that length of survival is primarily determined by initial diagnosis and age at diagnosis. Length of survival has not changed signifi- cantly since the beginning of the epidemic. VVR47 Lymphadenopathy: Update of a 60 Month Prospective Study. DONALD I. ABRAMS D.H. KIRN. D.W. FEIGAL AND P.A. VOLBERDING, San Francisco General Hospital, San Francisco, California USA Two hundred homosexual men with persistent generalized lymphadenopathy (PGL) of greater than 6 months' duration involving two or more extrainguinal sites were enrolled in this natural history study initiated in November 1981. Current morbidity status information is available on 143 men. of these, 47 (36%) have progressed to AIDS diagnoses. patients developed Pneumocystis pneumonia, 16 Kaposi‘s sarcoma and 4 other opportunistic infections. The percentage of patients developing AIDS after 24 months of PGL by product limit estimates Twenty-seven was 3.5% (i 1.5); 13% (:3,2) after 36 months; 32% (1 5.1) after 48 months and 45% (1 7.1) after 60 months. Significant factors predicting the development of AIDS include shrinking adenopathy; thrush or hairy leukoplakia; increased constitutional symptoms; peripheral cytopenias and an elevated erythrocyte sedimentation rate. Twenty—four of the'AIDS cases died with a mean survival of 12 months. Five additional deaths occurred in cohort members who developed HIV plus .17 AIDS 70% (50) 20% (14) 10% (7) Other Seropositives 27% (127) 48% (221) 25% (117) The mean slope of CD-A cells was downward among men developing IDS whose initial levels of 00-4 cells were <200, 200-499 and >499 cells/mm whereas the slopes among other seropositives demonstrated regression to the mean. The "flat" slope in men not developing AIDS suggests that CD-4 level may not he an appropriate surrogate for time since HIV infection. We did not follow these men from time of infection, therefore, some of those developing AIDS may have had a flat slope for some interval during the induction period. Nonetheless, these observations support the hypothesis that maintaining a stable level of CD-4 cells, even though it is at a lower level than seen among HIV negative men is a favorable prognostic sign over at least a period of 18 months. We will expand the data to include 1300 more HIV seropositive men from Baltimore, Chicago and Pittsburgh. WP65 Are absence or progressive loss of antibody to individual viral ' proteins of HIV, predictors for development of AIDS? M. IANGE, K.H. ONG, E.B. KLEIN, K. SHRIVER, L. GOLDSTEIN, L.Z. COOPER, St. Luke’s/ Roosevelt Hospital Center, Columbia University, New York, N.Y. and Genetic Systems, Seattle, Washington. A low level or complete disappearance of antibody to the human immunodeficien- cy virus has been reported by a number of investigators as a predictor of pro— gression towards overt clinical AIDS. In order to evaluate whether this ob- servation reflects a decreased antibody response to specific viral proteins, western blots (WB) and radioinmunoprecipitation assays (RIP) were performed on sera collected sequentially over a two year period from 10 AIDS patients and 26 HIV-pas subjects with or without lynphadenopathy (PGL) progressing to— wards overt AIDS and to ARC. 0f patients with AIDS, 9 had no response to P55, 6 hai noor weak (PW) response to p25 and 8 had an absent or PW to p15/17. 0f 26 HIV-pos patients at time of entry, 11 remained asynomatic with or without Lynphadenopathy (PGL). Only one had absent Ab to P55 whereas others had a good AB response to all viral proteins. of the 7 who progressed to overt AIDS most had an absent or progressively weaker AB response to P55 and P40 on west- ern blot and an absent or weak response to P40 and P18 on RIP. This abnormal response was frequently present 1 year or more prior to the development of overt AIDS. Using regular ELISA testing, no correlation was detected between ELISA values and absence or presence of antibody to the above viral proteins. Although titration was not attempted, one may assume that antibody for specific viral proteins may be precipitated in circulating inmune complexes frequently found in AIDS or ARC. In favor of this Hypothesis are our previously reported findings of presence of HIV antibody in CIC purified from sera of AIDS patients. WR66 Detection of Early HIV Seroconversion with Currently Available Serologic Techniques HOMAYOON FARZADEGAN*, E. Taylor*, N. odaka*, T-H. Lee**, R. Redfield***, B.F. Polk*, *Johns Hopkins School of Hygiene and Public Health, **Harvard School of Public Health, and ***walter Reed Army Institute of Research. Early immune responses to products of env and gag genes of HIV have not been investigated extensively in large numbers of newly infected persons. Serial sera were collected from 45 seroconverters participating in the Baltimore center of the Multicenter AIDS Cohort Study. Seroconversicn in this high risk group was defined as new and persistent appearance of antibody to » p24/gp41/gp>100 on immunoblot, or of antibody to p24/gplZO/gp160 by radio- immunoprecipiration assay (RIPA). We determined the sensitivity of seven EIA kits, two immunoblot kits and RIPA in detecting serologic markers of HIV infection at this early stage. The sensitivities of EIA kits were 76% to 92%; of the immunoblot kits, 82% to 96%; and of RIPA, 82%. of interest, p24 antigen was detected in the serum of 4 of 45 seroconverters at a visit six months prior to the visit at which presence of anti—HIV antibody was con- firmed. Seven participants had baseline sera with serologic evidence of early HIV infection. The EIA kits were positive in 0-4 of the seven; RIPA was positive in 3/1; and one immunoblot kit failed to detect antibody in any of the seven. We will discuss the probable sequence of serologic events in persons newly infected with HIV. These findings have important implications for the optimi- zation of serologic tests for early HIV infection, especially for application in blood banks. 121 wns1 Incidence and Significance of Persistent Generalized Lymphadenopathy in a Large Cohort of Gay/Bisexual Men RICHARD A. KASLOW, W.C.BLACKWELDER, J.P.PHAIR, D.LYTER, R.FOX, B.VISSCHER for the MULTICENTER AIDS COHORT STUDY(MACS), NIH, Bethesda, MD, USA Neither the incidence of new lymphadenopathy nor its place in the natural history of HIV infection is fully established. From 4 semiannual examinations during an 18-month interval, we have documented the incidence (Table) and examined the prognostic significance of persistent generalized lymphadeno- pathy (PGL) in HIV- men (Initial N=2635), seroconverters (Initial N=150), and HIV+ men (Initial N=1625). PGL at New PGL after entry: Cumulative entry (Z) 0—6 mo(Z) 7-12 mo(%) (12 mo) HIV(-) 3 2 1 3 Seroconverters ll 23 14 33 HIV(+) 30 ll 9 19 PGL was more common in men when their ELISA was last negative prior to se- roconversion (112) than in men whose negative ELISA remained unchanged for at least 6 months (3%)(p<0.001); early viral response could be an explanation. Seroconverters developed PGL at 2x the rate seen in men who were HIV+ for an unknown length of time and 10x the rate seen in those who remained HIV-. Prior to developing new PGL, previously HIV+ men closely resembled those without adenopathy in their mean CD4 and CD8 counts. During 12 months' fol- low-up, in neither HIV+ men nor seroconverters was the decline in C04 count related to the presence of adenopathy, and PGL did not alter the risk of AIDS. The incidence of PGL with new HIV infection is high, but its importance in the progression to serious immunodeficiency is not apparent. WP68 AIDS-Related Kaposi's Sarcoma in New York City in 1977 ' ROBERT J. BIGGAR*, PHILIP C. NASCA“, WILLIAM S. BURNETTH *National Cancer Institute, Bethesda, MD; **NY State Health Dept., Albany, NY New York City has been an epicenter of the AIDS epidemic since it was first reported in 1981, having both the earliest and the most cases of any city in the United States. We have shown that changes in the frequency of Kaposi's sarcoma (KS) cases among single young nen are a sensitive means of detecting the AIDS epidemic. In this study, we reviewed the KS cases among young hen <50 years old in New York City using data collected by the New York State Cancer Registry. Reliable data were available from 1973. Of 5 cases between 1973 and 1976 (1.25 cases per year), 4 were foreign born (including 1 from Puerto Rico), and were known to have been married. Four were also described as having disease of the the lower limbs compatible with classical, non-AIDS related KS. In 1977; both the frequency and the demographic/clinical patterns of KS among young New York men changed. 0f the 5 cases in that year, 3 were single men, all from the United States. In 1978, another single American-born cases occurred. In 1979, the recognized onset of the epidemic, 5 KS cases were reported, 4 of which were single. 0f the 6 cases in 1980, 4 were single; and of the 31 cases in 1981, 28 were single. Clinically, 2 of the 6 cases in 1977/78 were recorded in unusual sites for classical KS, ear and penis; 3 were recorded as having KS of the "skin"; and only 1 was recorded as having disease limited to the limbs. Three of these 6 cases, all single. were from lower Manhattan, although none of the earlier cases were. These data suggest that the AIDS epidemic emerged in New York City in 1977. WPBQ Association of Plasmids and Virulence of M cobacterium avium Complex W V- - .J‘m - AWFORD. J.M. BATES", *National Jewish Center for Immunology and Respiratory Medicine, Denver, Colorado, ”VA. Medical Center, Little Rock, Arkansas Organisms of me complex (MAC) cause pulmonary disease in humans and frequently encountered as opportunistic pathogens in Acquired Immunodeficiency Syndrome (AIDS) patients. Our studies comparing the MAC strains of AIDS patients with those from non-AIDS patients showed a possible relationship with the presence of plasmids in the MAC strains. We have shown that 100% of 26 AIDS strains and only one-third of 150 non-AIDS strains possessed plasmids. To obtain specific and direct evidence on the relationship of virulence to plasmid content, blind comparisons were undertaken to assess the virulence and associated parameters of MAC strain LR-25 which was shown to possess three (2 small and 1 large) plasmids and a strain derived from it, designated as LR-163, which has been cured of the three plasmids by acriflavin treatment. Strain LR-25 consistently caused high mortality (45%) of beige mice and CFU counts of the organisms from spleens and lungs, while the cured variant, LIZ-163, showed no mortality and low CFU counts. LR-ZS is thus classified as high virulent and LR-163, low virulent. Substantiation of the differences in virulence of this pair of strains was done by the release of oxygen metabolites from resident and activated mouse peritoneal macrophages. LR-ZS triggered 45 and 135 n.moles of 0; and 20 and 22 n.moles of H 02 from resident and activated macrophages; the corresponding figures for LR- 1 were 82 and 238 for 05 and 38 and 58 for H202. Based on our earlier finding of an inverse correlation With virulence, these studies with oxygen metabolites confirmed the loss of virulence when the plasmids were removed from the MAC strain LR-25. In contrast to the association with virulence, no significant changes with respect to drug susceptibility were noted within the two strains. WEDNESDAY, JUNE 3 WP") Clinical and Epidemiologic Characteristics of Ion—AIDS HIV—Belated Illness in IYC Hospitals EAR! All! CHIASSO'I. U. GARCIA, E. FLBISHBR, P. CRBBCH, SIOHBBURHEI, Flew York City Department of Health, llY, NY. The spectrum of HIV—related disease among hospitalized persons In New York City includes CDC defined A1 AIDS and other HIV—related illnesses (suspected AIDS). In order to describe the clinical and epidemiologic characteristics of this population of suspected AIDS cases. a point prevalence survey was conducted in March of 1986 at 25 hospitals that report 661. of AIDS mrbidity.'rhe average daily census at these hospitals for this month was 277 AIDS and 152 suspected AIDS cases. A total of 170 adult and 8 pediatric suspected AIDS cases were identified on the day of the survey. of these, 35 were females and In males; 541. black. 191. white, 271. Hispanic. The major risk groups were; 10‘ (591.) IVDUs and as (211.) gay/bisexual men. The proportion of “ms aomlg suspected AIDS cases was significantly greater(0k=3. p40 days cocultivation. Two patients receiving fresh frozen plasma of 2 donations positive for p24 , remained negative 6 months after transfusion, as tested by ELISA (2 kits) and IB. In Immunoblot Assays with HTLV-A and LAV /HIV encoded proteins. none of the donor samples showed reactivity cons sten with HTLV—A or LAV /HIV infection, i.e. envelope glycoproteins (P. Kanki, H. Essex, dept. of Cancer Biology Harvard University Boston, U.S.A., Diagnostic Pasteur, Marnes la Coquette, France). Reactivity against p21:gag of HIV in IB can persist for at least 2 years without signs of HIV—infection. In low risk populations this reactivity represents false positivity. WB74 Increasing Incidence of Tuberculosis in a Prison Inmate Population: Association with HIV Infection M. MILES BRAUN", B.I. TRUMAN*, G. WORMSER**, B. MAGUIRE***, R. BROADDUS***, D.L. HORSE*, *New York State Department of Health, Albany, NY, **New York Medical College, Valhalla, NY, ***New York State Department of Correctional Services, Albany, NY, USA. Concurrent with the AIDS epidemic, tuberculosis incidence rates in prison in- mates in New York State have risen 360% from 15.!» per 100,000 in 1976—78 to 70.9 per 100,000 in 1984-86 (provisional incidence of 105.5 in 1986). At the same time, AIDS incidence in inmates increased from 8.A per 100,000 in 1981 to 289.6 per 100,000 in 1986. To investigate the association between the large increases in these two diseases. we reviewed data from New York State's AIDS and TB registries. Over the past six years, 347 have been reported in inmates. cumulative AIDS and 112 cumulative TB cases No geographic clustering of TB cases was noted. Six percent of AIDS cases have had TB, and 20 percent of TB cases have had AIDS. By year of AIDS diagnosis, the number of AIDS cases with TB has increased from 0 in 1981—82, to 7 in 1983—84. and to 15 in 1985—86. of the 54 TB cases reported in 1985-86. 15 (28%) had AIDS, 15 (281) addition- al cases were HIV seropositive, and the reminder had unknown HIV antibody status. There were no reported seronegatives. Twenty—one (392) of the 54 had extrapulmonary TB, a finding often associated with HIV infection. These findings document an increasing rate of TB in prison inmates and strongly suggest its association with HIV infection. Standard TB control efforts should be intensified in order to reverse this increase in T3 rate. WP75 HIV ELISA Results in Heterosexual Partners of Persons at High I Risk for HIV Infection. JOHN WEBER', O. SIJIN‘, A. HARCBL", C. LYONS‘, s. LANDESMAN’. SUNY Health Science Center at Brooklyn, Brooklyn, N.Y. we have offered free confidential HIV counseling and testing (ELISA and Western Blot) in conjunction with the NYC Department of Health for a large urban population since 9/85. of the 430 patients that we have tested, 128 were heterosexual partners of bisexual men or intravenous drug abusers. None of these 128 individuals used "safe sex" methods. Ninety-six were women and 32 were men. Five of 96 women and 0/32 men had symptomatic HIV infection (AIDS, ARC or Gm). Twenty-eight of 128 (21.9‘) patients tested positive for HIV antibody, with confirmatory Western Blots. sixty of. 96 (62.50) women and 11/32 (34.3!) men reported sexual contacts with known HIV infected partners (AIDS, ARC] since 1983. Twenty-two of 60 (36.6!) of the women and 3/11 (27.2” men exposed to partners known to be HIV infected were HIV antibody positive. In comparison only 1/36 (2.8!) of the women and 2/21 (9.5“ of the men who reported heterosexual contact with high risk partners without evidence of symptomatic HIV infection were HIV antibody positive. while 36! (5/50) of the women whose reported risk was with high risk husbands were HIV positive, only 5/46 (10.9“ of the woman having had sex with high risk boyfriends tested positively. Heterosexual contact with high risk group individuals who are symptomatic for HIV infection carries a significantly higher risk of infection than contact with non symptomatic individuals. Women who have had long term relationships with members of high risk groups are more likely to be infected with HIV than those with short term relationships. WEDNESDAY, JUNE 3 Clinical Cour e of HIV-ser positive Homo exual Men VVE76 I i, V.L.Murphy2, .L.Robertsi, H.H. Handsfield ' , Universéty of Washington and Seattle-King Co. Dept. of Public Health , Seattle WA, USA. Estimates for progression to overt AIDS among HIV- seropositive(HIv+) homosexual men(HM) have varied from 10% to >30%, with an apparent increasing risk over time. We report follow-up on a cohort of 178 HIV+ HM enrolled in 1982-4. One hundred and seventy-eight(78%) were selected for the presence of persistent generalized lymphadenopathy(PGL); the rest were asymptomatic and had no PGL. Follow-up was 3-56 mo(median 42 mo). Twenty-five(14%) developed AIDS, an annualized rate of 4%; the annualized rates were 5% for HIV+HM with PGL(N=22) and 2% for HIV+HM without PGL(N=3). Using the date of documentation of HIV seropositivity, the risk of AIDS was higher at 4 yr than 1-3 yr, (P=o.03). Compared with the 153 HIV+HM who did not develop AIDS, the 25 who developgd AIDS had lower initial T4 cell counts(mean 285 vs 557/mm , P IV 61+D). Overall, AIDS developed in 9/124 pts (7%) after 4—24 months, including those 6 pts from group IV A+C2. A comparative analysis of progression rates (Kaplan-Meler method) showed - despite similar observation periods - that pts in group II had a signlficantly higher risk (p <0.01) for deterioration than pts In group 111. 13/27 pts with AIDS died, all of them had prior opportunistic infections (IV C1). Thus, 32/142 (22%) pts had evidence of progressive disease during this limited follow-up period. We conclude that HIV-associated morbidity - even for asymptomatic pts - is high. WEDNESDAY, JUNE 3 WP82 Update: Racial Differences between Patients with ' Hemophilia—Associated AIDS in the United States, 1981-1986. JEANETTE K. STEHR-GREEN, J. M. JASON, B. L. EVATT, Centers for Disease Control ICDC), Atlanta, GA. As of December 15, 1986, a total of 281 cases of hemophilia-associated AIDS had been reported to CDC. These cases represent a cumulative incidence rate of 1.6 AIDS cases per 100 persons with hemophilia. The number of AIDS cases diagnosed annually has nearly doubled, except in 1986, during which cases increased only 101; however, reporting is not yet complete for that period. Demographic characteristics of the patients diagnosed each year have not changed significantly. The majority of patients had severe hemophilia A (661) and had received commercially produced clotting factors (981). Of the 281 patients, the proportion of blacks was significantly lower than that of blacks in the general v.5. population (81 [22/281] vs. 12%, p-0.005). The median age for black patients was significantly lower than that for white patients (26 years vs. 34 years, p-0.02). Significantly more black than white patients had mild or moderately severe hemophilia (9/19 [47%] vs. 51/216 [242], p=0.02). Black patients were more likely than whites to have received plasma or packed red blood cells in addition to commercially produced concentrated clotting factors (7/17 {412} vs. 49/203 [2h2]); however, the difference was not significant. These data suggest that AIDS is diagnosed less frequently among black hemophiliacs than white and are consistent with a higher early mortality rate among black hemophiliacs due to their coagulation disorder or the presence of racial cofactors for the development of AIDS. However, population—based studies are needed to better define these racial differences. WR83 A Three Year Prospective Study of Initially Asymptomatic HIV Posi— tive Gay Men in Stockholm, Sweden. ANDERS KARLSSUN, L MORFELDT-MANSSDN, B BUTTIGER, G v KRDGH, L MDBERG, E SAND— STRUM, et al., Venhalsan, Dept of Dermatovenereol, deersjukhuset, Roslags— tulls Hospital, Dept of Immunol, The Natl Bacteriol Lab, Stockholm, Sweden. In a health screening project in Stockholm, Sweden, consecutive asymptomatic gay men have been enrolled and prospectively followed since Nov 1982. Frozen coded sera from 998 men, drawn during the period Nov 1982 to Dec 1983, have been examined for serum antibodies to Human Immunodeficiency Virus (HIV) by ELISA. Positive reactions were confirmed by Western blotting. The seropositive men have been followed and their clinical status three years later is presen— ted. Repeated determination of T cell subsets were done in most men. Results: HIV antibodies were demonstrated in 123 (12.}%) of the 998 men. 0f the seropositive men it was possible to evaluate 116 men after a mean time of h0.6 months. of these 116 men, 19 (16.4%) had developed AIDS. Eleven of the men with AIDS had died. Of the men without AIDS it was possible to clinically evaluate 80. Of those, 8 (10.0%) had AIDS Related Complex (ARC), 38 (47.5%) had Persistent Generalized Lymphadenopathy (PGL) and 33 (41.}%) had a minor lymphadenopathy (ML) or were completely asymptomatic. One man (1.2%) had died of and one man with ML had been treated for Malignant melanoma. 0f the men diagnosed as having AIDS, 8 had Pneumocystis carinii pneumonia, 5 Kaposi's sarcoma (KS), 2 CMV infection, 1 Candida esoephagitis, 1 Toxoplasmosis, 1 Cryptococcus meningitis and 1 both KS and Lymphoma at the time of diagnosis. Conclusion: This study shows that the morbidity and mortality of HIV infec— tion is high even in recently infected individuals living in a country with a high standard of living and good health services like Sweden. T cell subsets as prognostic markers will be discussed. “VP84 Antibodies to HIV in Cervical and Oral Secretions of ' Female Prostitutes in Zaire DAVID W. ARCHIBALD*, M. ESSEX**, J. SAUK*, J. MANN***, H. FRANCIS**;*, T. QUINN****, et al., *University of Maryland Dental School, Baltimore, MD, **Harvard School of Public Health, Boston, MA, ***Department of Public Health, Kinshasa, Zaire, CDC, Atlanta, GA, ****Laboratory of Immunoregulation, NIAID, NIH, Bethesda, MD. The antibody response to HIV in cervical and oral secretions was studied in a cohort of high risk African individuals. The population assayed consisted of HIV seropositive and seronegative active female prostitutes from Zaire. Oral secretions were collect ed by rinsing the subjects' mouths with PBS followed by expectora- tion. Cervical secretions were collected by adding a cervical scraping to an aliquot of PBS. Secretions were assayed for anti— ggdies using a modified,IgA-enhancing radioimmunoprecipitation of S-cysteine-labeled Molt HIV-infected cell lysates. Seventeen of 22 cervical samples and 19 of 22 oral samples from the seropositive individuals contained antibodies to viral anti- gens. Antibodies to gplso, gp120, and p24 were consistently found. One seropositive individual had no detectable antibodies in either secretion. Secretory antibodies were not detected in the oral se— cretions of 21 seronegative individuals. One of 21 cervical from seronegative prostitutes showed a weak precipitation of gp160 and 120. We have demonstrated that 21 of 22 serpositive women possess viral—specific antibodies in their oral and/or genital secretions. The presence of antibodies at mucosal surfaces may be associated with the lower incidence of female to male transmission of AIDS. 124 WR85 Serial Western Blot Analysis in the Early Diagnosis of HIV Infec- tion FRITZ DAGUILLARD*, P. STRICTLAND*, T. LOG*, C. LANE**, M. WELLS***, AND D. SHEPP***, *Commission of Public Health, Washington, DC, **NIH, and ***FDA, Bethesda, MD. Ten individuals (2 males and 8 females) presented for testing following repeated heterosexual exposure to an HIVpositive partner. Last intercourse had occured 6 months to several days before testing. Only 1 patient was initially reactive by ELISA (Abbott). Western blot analysis revealed a weak p2A band in one case (#1) and a weak p55 band in two other cases (#2 and 3). In each case the absorbance value of the ELISA was clearly negative. All but one patient agreed to return for a regular follow-up which included HIV antibody testing, viral culture and an extensive immune profile. Patient 1 did not return for evaluation before 6 months. At that time ELISA and Western blot were strongly positive. Patients 2 and 3 were evaluated 3 months later. In both cases bands reactive to all gag protein antigens were identified by Western blot, while the ELISA test was still negative. Viral culture was negative in both cases. All the other patients have remained negative by both ELISA and Western blot when tested 1 to 4 times over a period of 3 to 15 months. In all 9 patients the immune parameters were within normal limits. These results suggest that serial Western blot analysis which does not over- look weak p55 and/or p24 bands is the most sensitive way to diagnose early HIV infection. “vase Immunological Progression of HIV Infection in Sydney Gay Men—-A Generalised Linear Model J.BURCHAM*,R.PENNY**,G.BERRY‘,B.TINDALL**,D.COOPER** *University of Sydney,'*Centre for Immunology (St. Vincent's Hospital) Sydney, Australia Over a period of three years, the Sydney AIDS Prospective Study has collected epidemiologic, clinical, serological and immunological data, in six-monthly visits, from over 1000 homosexual men, of whom 40% are HIV ABV positive. In over 85% of the HIV ABV positive subjects, this longitudinal study finds the linear sequence immunological progression of the disease to be low Td/TB ratio, low T48, to low T4 count, and finally low lymphocyte count, confirming the stages found by Zolla‘Panser in a cross-sectional study. A very significant correlation was found between this progression and the rate of change of T4 cell count with respect to time, suggesting that each step in the progression is determined predominantly by T4 changes. Each of the stages of immunological progression where analysed in relation to clinical features which varied from asymptomatic to LAS, ARC, and AIDS. Using logistic regression and linear modelling tools, no correlation was found between clinical and laboratory findings, nor between lifestyle factors and immunological progression. The highly variable relationship between clinical findings and immunological changes indicate that a much more complex branching model of the disease is needed to predict outcome. VVBB7 HIV Infection in Dialysis Centres. U. ASSOGBA*, M. REY**, R.A. ANCELLE***, C. FOUCAULT*, J. ROTENBOURG*, J.C. GLUCKMANN*, *Dept. nephrology, Hopital Pitié Salpétriére, Paris, ** Dept. virology, Hépital Claude Bernard, Paris, ***WHO Collaborating Centre on AIDS, Paris, France. A prospective multicentre study was undertaken between February 1985 and August 1986 in 4 haemodialysis centres in the Paris area (France) in order to assess the prevalence of HIV infection and the risk of transmission of the virus within the centres. A four- month follow—up was carried out in 221 patients undergoing haemo- dialysis (HD) and in 40 staff members caring for the patients in 2 centres. 62 patients undergoing peritoneal dialysis (PD) and 126 haemodialysis patients who transited through a centre (HDT) were screened once. A questionnaire exploring risk factors was completed for each patient and staff member. Sera were tested for HIV antibodies by ELISA (ELAVIA) and confirmed by Western Blot. Of the 357 HD+HDT patients, 4 were found to be positive. Of the 221 HD patients, 1 multi-transfused haemophiliac and 1 multi- transfused Nigerien without other risk factors were positive in the first screening. Another patient seroconverted after trans- fusion during the study; no other risk factors existed and the donor has not yet been found. One of the 126 HDT patients had received infected plasma. No staff members or PD patients were positive. No transmission within centres, from patient—to-patient or patient-to-staff was evidenced. Although HIV seems to be less infectious than HBV, precautions to prevent transmission of HIV in dialysis centres should be maintained. WEDNESDAY, JUNE 3 wpsa The Impact of Presumptively Diagnosed Opportunistic Infections and ' Cancers on National Reporting of AIDS E. THOMAS STARCHER II.,* J. K. EIEL,** R. RIVERA CASTANO,*** J.M. DAY,**** 5.6. HOPKINS,***** J.W. MILLER******. *Centers for Disease Control, Departments of Health of **New Jersey,***Puerto Rico,****Boston, Massachusetts, *****Washington, and ******Connecticut, USA A review of death certificates in four U.S. cities suggested that at least 10% of AIDS cases do not meet the national surveillance case definition because of the lack of biopsy or other specific confirmation of the indicative disease and are therefore unreportable. To assess the frequency of the resulting underreporting, health departments in five areas of the United States reviewed medical records for all or for a random sample of patients treated during a fixed time period who 1) had previously been considered as suspected AIDS patients and/or 2) had discharge diagnoses consistent with the various AIDS indicative diseases. Extrapolations from preliminary results in four areas suggest that 96 AIDS cases were presumptively diagnosed during the same period that 723 cases were definitively diagnosed, for an overall llZ rate of presumptive diagnoses, ranging by area from 4% to 152. Information from the fifth area suggests the rate there may exceed 501. Coincidentally, the studies identified 58 (7%) previously unreported AIDS cases that meet the national surveillance case definition, consistent with results from validation studies elsewhere. When data analysis is completed in March, we will estimate the impact on national AIDS surveillance of not reporting presumptively diagnosed AIDS cases. The study will also 1) identify reasons presumptive rather than definitive diagnostic methods are used, 2) determine which opportunistic infections and cancers are presumptively diagnosed most often, 3) indicate trends over time in the frequency of presumptive diagnosis, and 4) estimate the usefulness of retrospective chart review in identifying unreported AIDS cases. WR89 CD4 + cells' count as predictive marker of disease progression in HIV-positive parenteral drug addicts. MASSIMO GALLI, G. TAMBUSSI, A. CASTAGNA, A. SARACCO, M. MAILLARD, A. LAZZARIN, et al., Clinic of Infectious Diseases, University of Milan, Italy. CD4 + cells‘ count in peripheral blood is considered a valuable predictive marker of clinical evolution in HIV infections. A clinical survey of 375 parefl teral drug addicts (PDAs) examined between 1884 and 1986 was performed. All studied subjects (279 males. 96 females, age ranging between 18 and 33) sharing behavioural, social and toxicomanic habits, live in Milan, where the first HIV seroconversion in PDAs was documented in 1979. A clinical classification was made following CDC‘s and Walter Reed Foundation's criteria. T cell subsets were determined by an Ortho spectrum III cytofluorograph. Mean counts of CD4 + cells in the overall population showed a significant decrease during the three years of the study (from 986.5 ; 642.1 in 1984 to 491.9 1 2 4.3 in 1986, p< 0.001% In order to evaluate decreasing chances (below 400/mm ) of CD4 + cells in 108 already symptomatic patients, we considered as conventional starting point for a subsequent follow—up the onset of a histologically confirmed lymphadenopathy syndrome (LAS). 0 co diagnosis of LAS was made, CD4 + cells' chances of decreg sing below 400/mm were 50% after 32 months. Our data confirm on the one hand the trend to a rapid decrease of peripheral CD4 + cells in the overall popula— tion of HIV infected PDAs, on the other hand, the regatively long average time required by CD4 + cells to reach levels below 400/mm in symptomatic subjects, pointing to a possible slow progression of the disease. A Computer Model of the AIDS Epidemic vvngo DAVID J. AHLGREN, Ph.D., ALEX STEIN: PETER LYONS; Department of Engineering and Computer Science, Trinity College, Hartford, CT 06106. This model tracks the spread of AIDS through the sexually active population, quantifies the effect of such disease carriers as intravenous drug users, bisexuals, and hemophiliacs, predicts infection and mortality, and evaluates the sensitivity of the epidemic to policy and behavioral changes. These include improved educational programs, changes in sexual habits, provision of sterile needles to intravenous drug users, application of disease- inhibiting drugs, implementation of testing programs, and reduction of the likelihood of disease transmission through prophylaxis. The model divides the sample population into three categories: homosexuals, bisexuals, and heterosexuals. Each category includes intravenous drug users and hemophiliacs. The transmission of AIDS through sexual interaction, needle sharing, and blood trans- fusions is characterized by a set of non-linear equations which are solved using the STELLA simulation language on an Apple Macintoshmicrocomputer. whenguantifiedbyUnitedStatesaggregate data from the National Centers for Disease Control, the model predicts a peak in the AIDS-infected population in 1991 accompanied by the devastation of the bisexual and intravenous drug using populations, and demonstrates the relative insensitivity of the epidemic to increased sexual frequency and to increased number of partners. We will show how to apply the model to a particular region by describing a ten—year simulation of AIDS in New York City. 125 VVR91 "omen with the Acquired Immunodeficiency Syndrome in Miami MARGARET A; FISCHL and GM DICKINSON. University of Miami, Miami, FL Miami reports the fifth highest number of cases of AIDS in the United States, including one of the highest percentage of women with AIDS. During the past 3 years, 111 women were diagnosed with AIDS at our medical center. Ten were caucasisn and 101 were black, ranging in age from 20 to 57 years. Risk factors for AIDS included intravenous drug abuse (43% heterosexual contact with a person at risk for AIDS (8), blood transfusions (7), and 50 women of Haitian ancestry. The number of cases and associated risks factors per year are listed below: Intravenous Heterosexual Blood Haitian Years lumber Drug use contacts Transfusion Unknown ancestry 1983 17 4 l 1 0 11 1984 17 9 1 1 0 6 1985 31 12 3 2 1 13 1986 46 18 3 3 2 20 Ninety-eight presented with opportunistic infections including 31 with multiple infections, 14 with opportunistic infections and Kaposi's sarcoma, and one each with Kaposi's sarcoma or lymphoma. The types of infections included: 3; carinii pneumonia (73), toxoplasms encephalitis (21), M; avium- complex infection (7), cytomegalovirus infection (10% Cryptococcosis (10% and Cryptosporidioais (9). Associated infection with oral thrush (63L genital herpes (32), and herpes zoster (4) were also found. Six women presented with AIDS during pregnancy, and 18 reported a history of miscarriage. The average length of survival after diagnosis was 6.6 months, ranging from 1 to 23 months. AIDS among women appears to be increasing, is disproportionately associated with multiple infections and has a poor outcome. WR92 The Melbourne Cohort After 3 Years: Halt of Sara-conversion to HIV and Predictors of Immune-Deficiency. BRIAN P. MULHALL‘, R.M. CRAPPER**. I.H. FRAZER ***, I.R. MACKAY *, The Walter & Eliza Institute, Melbourne, Australia **, Institute of Bone & Joint Disease, New York, U.S.A. ***, Princess Alexandra Hospital, Brisbane, Australia. In 1983 a cohort of 100 asymptomatic homosexual men was recruited for a prospective study. HIV seroconversion and immune function assessments included T Lymphocyte subsets, including helper—inducer (CD4 + 434) and suppressor inducer (CD4 + 2H4+) cells, serum immunoglobulins, and capacity for recall of delayed hypersensitivity. The prevalence of antibody to HIV rose from 22% in 1983 to 31% (24/78) in 1985. There has been no further seroconversion in 1986, suggesting that the spread of virus into and within this group has been halted. We have analysed the immunologic parameters from visits 1-8 to determine whether there are continuing group trends, single measurements are predictive, or whether for a single individual serial measurements have better predictive value. For T helper (Leu 3) subset numbers, correlation analysis between visits followed by simple linear regression was not significant (p=0.15). However, t tests for repeated measurements on same individuals was significant in the seropositive group (t=2.la, p=0.03). similarly, for serum immunoglobu- 1in concentrations, only the t test for repeated measurements in the sero— positive group was significant (t=3.59, p=0.002). These results indicate that although there are clear group trends, for a single indivual, serial and not point-measurements are necesssary to predict immunodeficiency. VVR93 Novel Phenomena in Epidemics Associated with Long Incubation Periods:*Application to AIDS JOSE J. GONZALEZ , M.G. KOCH AID, Grimstad, Karlsborg, Sweden. The onset of any epidemic associated with a disease having long incubation periods displays a behavior which is well—known from acoustics and electronics: a transient appears, meaning that the pattern of the observed epidemlc does not mirror exactly the spread of the infectious agent during an initial phase of the order of the breadth of the incubation period distribution. For instance, a fictitious disease having an incubation period between 1 and 5 years with a mean incubation period of 3 years whose agent (a virus, say) spreads with a constant doubling time of 12 months leads to an epidemic starting with a doubling time of only 6 months. The doubling time of the observed numbers of cases increases during a 5 year period until it becomes equal to the doubling time in the number of virus carriers (12 months). Such an onset transient is very important for AIDS. Here, the extremely long mean value and the large variance of the incubat— ion period distribution imply that during an initial stage which may last up to 7 years most of the observed increase in the doubling time of AIDS cases is a spurious effect. This is shown with numerous examples for different compartments and countries. Genuine drops in the rate of spread of HIV induce again negative transients which must be taken into account in order to achieve a real un erstanding of the epidemic pattern. Norway, *véc, WEDNESDAY, JUNE 3 WR94 Evidence for Heterosexual Transmission of HIV in the United Kingdom ANDREW D. PEARSON, and N.S. GALBRAITH, Communicable Disease Surveillance Centre, PHLS, London, UNITED KINGDOM. Heterosexual transmission of HIV is presumed to have occurred in 18/610 (3%) AIDS cases and in 48/3870 (1.2%) HIV antibody positive individuals reported to CDSC between 1982 and 1986. The 18 AIDS cases were associated, predominately, with people whose hetero- sexual contacts or residents were abroad(14/18). The other four cases were "UK acquired': One case from a haemophiliac, the second case a prostitute with American contacts, the third was an African living in England since 1963, and the fourth was a male with multiple partners, including prostitutes, but who had shared razors with drug users. The 48 HIV antibody positive individ— uals most probably contracted their infection as follows: 15 from haemophil— iacs (31%), 8 from contactsabroad (17%), 6 from prostitutes within Europe (13%), 5 from contact with IV drug abusers (10%) and four from AIDS cases or HIV antibody positive husbands: One had a boyfriend with American contacts; one was a wife of a bisexual man, two had a history of prosmiscuity, one with Dutch contacts; and 5 individuals from whom the contacts are still being sought. Four groups make up 79% (52/66) of the reported heterosexually acquired in— fections; the British visiting or living in Africa (19/66), and the partners of haemophiliacs (16/66), prostitutes and their contacts (8/66) and the sexual partners of IV drug users (5/66). The AIDS cases and HIV infections occurred 1 in 1982, 4 in 1983, 3 in 1984, 16 in 1985 and 42 in 1986. The actual number of heterosexual infections is unknown but this data is un- equivocable. The 'heterosexual' outbreak of AIDS has started in the UK. Surveillance and practical intervention will be discussed in the context of these findings. WR95 HIV INFEEIION AMONG FENALE AND MALE PROSTITUTES. U.Tirelli, E.Vaccher. 5.0iodato, R: Bosio, P.De Paoli, D.Crotti et 3]. AIDS and Related Syndromes Study Group. Centro di Riferimento Oncologico, Aviano, Italy. Between September 1985 and January 1987, we carried out a prospective study in 36 female prosti— tutes, 22 of whom were intravenous drug abusers (IVDA), and in 15 male prostitutes, 3 of whom were IVDA, 9 transvestites and 3 homosexual men, in Pordenone and lreviso. tun towns of Northanst Italy. The prostitutes were clinically examined, given laboratory tests including HIV antibody tests (Elisa with Western Blot confirmation) and Th/l8 ratios and completed a questionnaire on their sexual behaviour. ReSulAE FEMALE PROSIIIUIES MALE PROSIITUTES IVDA NON—IVDA lVDA NON-IVDA ("=22) (nalk) (n-3) (n-lZ) Median age (yr) 2A 37 26 25 H ' d t f pigéii‘tui‘iin‘llrl 2 10 1 8 Median partners / mo 70 90 NA 150 Rectal intercourse “X 7% 100% 100% Frequency of: HIV antibody 59% 0% 33% 3% AIDS 0 0% 0% 0% Our data shows that female prostitutes who are not IVDA and male prostitutes who are not homosexual are not at increased risk for AIDE while female and male prostitutes who are lVDA should be considered at risk For HIV infection. wags Immunological, Serological and Clinical Abnormalities in Children Born to Promiscuous and Drug-Addicted Mothers at Risk for AIDS. EDUARDO FERNANDEZ-CRUZ, A. FERNANDEZ. D. GURBINDO, M. GARCIA MONTES and J.M. ZABAY. Hospital Provincial. Complutense University. Madrid. Spain. Two different enzyme-linked immunoassays and indirect immunofluorescence or Western blot tests were used to evaluate HIV seropositivity in 201 I.V. drug abu- sers. In this population, 892 (71% males and 182 females) were considered to have HIV antibodies. We studied 45 infants and children (ranging from 1 month to 6 years of age) born to drug-addicted and sexually promiscuous mothers. Thirty-six percent were found to be HIV-positive. Furthermore, 9 of 15 children born to drug -addict mothers (602) and 3 of 20 born to sexually promiscuous (102), were sero- positive. The other 4 affected children were born to heterosexual mothers with partners in the at-risk groups. Twenty-nine (64%) were HIV-negative children without clinical signs, but with increased (A32) and decreased (29%) Th/TB ratio, reduced PWM response (502), but normal serum levels of Igs. The other 16 were HIV—positive, and of these 4 (24%) had asymptomatic infection and 12 (752) were included in group IV as clasified by CDC (2 had AIDS, 7 had ARC and the other 3 were group IV-E). In the HIV-(+) group all children showed a significant increase of IgG as compared with HIV-(-) group (p<0.01), and there was a significant di- fference in IgA levels between HIV-(+) group IV and HIV-(+) asymptomatic children (p<0.05). A11 HIV-(+) children in group IV showed a progressive drop in T helper cell numbers (892) and TA/TS ratio (1001) and decrease in blastogenic response to PWM (1002). Children of the HIV-(+) group IV also showed infection by other viru- ses (202 were HbsAg—(+) and 332 had antibody to hepatitis B core antigen). of special note is the fact that in children of the HIV-(+) group IV, 692 had been immunized with the usual vaccines as compared with only 252 in the asymptomatic HIV—(+) group. Further investigations are in progress to elucidate which co-fac- tors might be involved in the evolution of AIDS in children at-risk. 126 WRQ'] Utilization of the Highly Permissive C3 Cell Line in Rapid Serum Neutralization Assays. W. EDWARD ROBINSON, DAVID C. MONTEFIORI, and WILLIAM M. MITCHELL, Vanderbilt Unwersit , Nashville, Tennessee, USA. The HTLV-ll transformed cell line C3 is highly permissive to HIV infection i3 vitro. Even in the presence of low MOI (0.01-0.1), this cell line exhibits rapid expression of viral antigens in 4-6 days with extensive cell lysis as early as 7-9 days post virus adsorption. Utilizing the C3 cell line, a rapid neutralizing antibody screen is now described. Demonstrated are results derived from patient sera obtained durin the course of antiviral drug therapy. Using either an increase in time to cyto ysis, reduction in reverse transcriptase assay values, or reduction in percent indirect immunofluorescence as the criteria for neutralization of virus, it is possible to clearly demonstrate significant differences in the anti-HIV qualities of different patient sera. Some patients show significant neutralizing ability with either percent fluorescent cells or reverse transcriptase levels less than thirty percent of HIV infected control. Other patients show virtually no ability to neutralize HIV with RT assay values or percent fluorescence eighty percent of control values. Therefore, utilizing standard neutralizing antibody titer techniques but incorporating the C3 cell line, it is possible to completely evaluate patient serum in seven days. The rapidity with which this cell line expresses viral antigens makes the C3 the cell line of choice in serum testing especially when large numbers of sera must be evaluated. VVP98 Cleavage of C3 Complement in the Serum of AIDS or AIDS ' Related Complex (ARC) Patients V.A. PASECHNIK*, S.V. ANDREVEV*, A.M. ISCHENKO*, S.A. KETLINSKV*, E.V. KARAMOV**, V.M. ZHQAMQV**. *Institute of Highly Pure Biopre- parations, Ministry of Medicine and Microbiology, Leningrad, ** Ivanovsky Institute of Virology, Academy of Medical Sciences of USSR Moscow C3 deficiency leads to chronical diseases. It was extremely interesting to study C3 in patients with AIDS.27 sera of AIDS and ARC patients were examined by Western blot analysis using 125 1 labeled anti-C3 monoclonal antibodies (LBP 610) specific to nati- ve C3 molecule and its C33 fragment (Mr=9,2kD). In 26 sera C3 protein bands were detected at a level of few percents and in one case Its amount was about ten percents of that in normal serum. In 20 sera two intense bands, corresponding to Hr=9.2kD and Mr= 8.3 kD were found. The latter fragment was not previously descri- bed in the process of C3 cleavage. In two sera only this fragment was detected and 5 sera did not contain C33 specific fragments at all. In some sera the other C3a containing fragment with Mr= 140 kD was present. C3 component may be cleft by the virus and/ or cell protcases produced during cell destruction. Enhanced cleavage of C3 complement component may be a new important factor in the development pathogenicity of HIV Induced immunodeficiency. wags Failure to Demonstrate HIV-Specific CTL in Asymptomatic Antibody-Positive Homosexual Men. ALISON C. MAWLE, J.A. SCHEPPLER, T.J. SPIRA, J.S. MCDOUGAL, Centers for Disease Control, Atlanta, GA. We have attempted to generate human immunodeficiency virus (HIV)-speciflc cytotoxic T-lymphocytes (CTL) from 18 antibody—positive asymptomatic homosexual men. This population has been shown to have elevated numbers of cytotoxic precursor cells (Leu 2*, Leu 15‘). The mean CD8+ cell number of the group studied was 839:346 per mm3 (normal range 192-726), with 501 being above the normal range. Sixteen had an inverted CDAICDB ratio (x-0.77) and the mean CD4+ cell number was 6331259 per mm3 (normal range (468-1433). PBL were cultured with live virus for 7-14 days, then assayed for killer activity on infected autologous monocytes, infected autologous CD4+ FHA—stimulated blasts, or 606* PHA-atimulated blasts with virus bound to the cell surface. In some experiments we added either IL-2 or irradiated allogeneic PBL to the culture in an attempt to supply any factors necessary for CTL production. We also tried to reatlmulate primary cultures with irradiated HIV—infected autologous FHA-stimulated blasts. We detected no HIV-specific CTL under any of these conditions. Cultures with infectious HIV did not abrogate the generation of EBV-specific cytotoxic cells from normal individuals. Since CTL specific for other human viruses, such as influenza, EBV and CMV, are generated under similar conditions to these, we conclude that under conditions that normally allow CTL generation in humans, HIV-specific CTL are not detectable. WEDNESDAY, JUNE 3 Mice Depleted In Vivo of "T4" Lymphocytes Do Not Die of Infection With Ectromelia vaccinia or tomegalovirus* * GnM. SHEARZR , M. BULLE} , A. §9SENBERG , T. MIZUOCHI , C. S. VIA , B. WEATHERLY , et a1., NCI , NIAID , NIH, Bethesda, MD. Many AIDS patients do not generate in vitro T cell responses to virus (self restricted antigen, S+X), but exhibit elevated T cell responses to HLA allo- antigens (ALLCD (J. Immunol. 137:2514, 1986). Terminal AIDS patients, however, appear to have also lost their in vitro ALLO responses. This difference raises the possibility that the 604— T cell pathway responsibile for the ALLO reac- tivity provides some protection in AIDS patients. lbrine in vitro T cell responses to (S+X) require UTA+ (CD4) helpers, whereas ALLO responses can be generated by Lyt2+ (CD8) helper cells (J. Exp. Med. 162:427, 1985). Because of this similarity in the T helper pathways of the two species, we have tested the possibility that mice depleted in vivo of either 1.31%+ or of both L3'Ifi+ and Lyt2+ cells will be susceptibile or resistant to the murine pathogenic viruses ectromelia, vaccinia, and cytomegalovirus (CMV). Mice in which both T cell pathways were intact generated T cell and antibody responses to these viruses and were resistant to the infections. Mice depleted of both L3TA and LytZ cells did not generate T cell or antibody responses and died soon after exposure to ectromelia or CMV. However, mice selectively depleted in vivo of L3T4 cells and subsequently infected with ectromelia, vaccinia or CMV gener- ated T cell responses, did not make antibodies, but did not die from virus infection. Further, studies of the CMV infected mice indicated that CMV could be detected in the salivary glands and spleens of mice depleted of L3’l‘4+ cells or of both L311.+ and Lyt2+ cells, but virus was much more extensive in mice depleted of both subsets. These in vivo studies of selective "T4" depletion in mice raises the possibility that the elevated T4 independent pathway pro— vides some immune protection_in the AIDS patient. WP.100 wP1o1 Further Investigation of a Suppressive Factor Associated with HIV. ' B.Hofmann, E.LANGHOFF, 00 LINDHARDT, K.ULRICH, JJ HYLDIG-NIELSEN, A.SVEJGAARD ET AL. UNIVERSITY HOSPITAL (RIGSHDSPITALET), COPENHAGEN, DENMARK. We and others have earlier shown that a purified Triton-X treated extract of HTLV—III suppress the lymphocyte transformation response of normal lymphocytes to mitogens and antigens, whereas an extract of uninfected H9 cells do not. We have now shown that the suppressive factor is also present in non-Triton—X treated virus preparation and in preparations from the M36 cell line known not to be mycoplasma—infected, which exclude these trivial explanations for the suppression. Moreover, the extract did not contain demonstrable amounts of tumor necrosis factor or lymphotoxin indicating that it is not of cellular origin. It suppresses all cells studied of hematopoietic origin,including the formation of colony forming units from human bone marrow, but not fibroblasts. It has a MV of about 70.000 on Sephadex separation. Preincubation of lymphocytes with the extract before adding mitogen gives pronounced suppression, while addition of extract three days after mitogen has little effect indicating that the factor acts early. It compleately inhibits IL-2 receptor expression. It‘s action cannot be blocked by addition of IL-1, IL-2, or by commercial antibodies against p2a, gphl, or gp 120, and it does not inhibit the binding of antibodies against CD4, CD8, or the lL-2 receptor. Sera from some anti-HIV positive and clinically healthy individuals can neutralize the suppressive effect of the HIV-extract on lymphocyte transformation. This neutralizing effect was recovered in ammonium— precipitated immunoglobulin from the same individuals. Further investigation of antibody preparations from these sera are currently under study. (This work was supported by the Danish Cancer Society and the Danish Medical Council.) WP102 Serial Testing of Cell—Mediated Immunity in Haemophiliacs. ' ROBERT J.G. CUTHBERT‘, J. TUCKER*, C.M. STEEL**, J.F. PEUTHERER***, C.A. LUDLAM'. ”Dept. of Haematology, Royal Infirmary of Edinburgh. ”MRC Clinical Population and Cytogenetics Unit, Western General Hospital, Edinburgh. ‘*'Dept. of Bacteriology, University of Edinburgh. Cell-mediated immunity (CMI) was assessed in 39 haemophiliacs by intradermal response to 7 recall antigens and compared with 20 healthy male controls. A positive response was indicated by mean diameter of induration ;>2mm at day 3. All control subjects were positive to 2 or more antigens and 80% responded to 4 or more. CMI was markedly depressed in the haemophiliacs with 62% responding to none or one antigen and only 18% responding to 4 or more. Eighteen anti-HIV positive patients showed no significant difference in responsiveness compared with 21 anti—HIV negative patients. However there was an inverse relationship between annual factor VIII consumption and the number of positive responses. Twenty—seven of the patients had been exposed to a single batch of factor VIII contaminated with HIV; 14 developed anti-HIV antibodies and 13 remained seronegative. Skin testing 3-9 months following exposure to this batch showed no significant difference in responsiveness between seropositive patients and those who remained seronegative. Ten patients have been re-tested 2% years after exposure. Three symptomatic anti-HIV positive patients are now anergic (1 with AIDS, 2 with ARC) whereas 2 asymptomatic seropositive and 5 seronegative patients have maintained their cell—mediated responses. Depressed CMI in haemophiliacs can be correlated with factor VIII usage. In the early period following exposure to HIV no difference in CMI exists between seropositive and seronegative groups. An increased prevalence of energy is associated with symptomatic HIV infection. 127 Restoration of AIDS defective Natural Killer (NK) fungtlon by OK-432 _ BENJAMIN BONAVIDA°, JONATHAN D. KATZ , ARTO HADDADIAN , MICHAEL S. §0TTLIEB , M , AND IAKASHI H05HINO‘: From the Departments of Microbiology and Immunology, and Medicine, UCLA School of Medicine, Los Angeles, CA 90024 and +the Department of Immunology, Fukui Medical School, Japan. We have recently reported that the mechanism of depressed NK activity in AIDS PBL is due to a defective "trigger-receptor" for target cell stimulation and which canbe functionally restored by IL-2 (J. Immunol. 137:1157, 1986). We have also reported that the biological response modifier 0K:I§2 (a low viru- lent strain of Group A Stre tococcus o enes), augments NK—CMC activity and secretion of NKCF by NK ce 5 Its lular mmunol. 102:126, 1986). These DK-432 activation events appear to be independent of IL-Z‘But mimic the effects of IFN and IL-2 activations of NK cells. The present study examines whether 0K-432, like IL-Z, can also activate AIDS NK activity. PBL from patients with AIDS/KS were treated with OK-432 for 20h, washed and tested against the NK sensitive GS target cells in a 4h 51Cr release assay. A significant enchan- cement of NK activity was observed which was dependent on the dose of 0K-432 used. We also observed a significant enhancement of ADCC activity. These results demonstrate that OK-432 restores AIDS NK activity presumably through the same mechanism induced by IL-2. The mechanism of 0K432 mediated activa- tion of AIDS NK cells will be presented. (This work was supported in part by a grant from the AIDS Task Force, and in part by the Tumor immunology training grant CA-OSIZO awarded to J.D.K.) WP.103 WE104 Detection of Antibody Dependent Cell Mediated Cytotoxicity (ADCC) Against Human Immunodeficiency Virus (HIV) Infected Cells. R S. BLUMBERG, TIMOIHZ J, P535215, K.L. HARTSHORN, M.W. VOGT, M.S. HIRSCH, R.T. SCHOOLEY. Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114:. We studied the ability of serum from HIV seropositive or seronegative subjects to augment killing of HIV infected H9 cells compared to uninfected H9 cells in a 7 hour chromium release assay using peripheral blood mononuclear cells from healthy HIV uninfected donors. HIV infected H9 cells were more readily lysed than uninfected cells, supporting observations by others regarding NK activity against HIV infected cells. Much greater augmentation of killing of HIV infected H9 cells compared to uninfected cells was observed using serum from HIV infected donors. Ierss£_§ell Segum 3 fig H9fiflIV (H91HIVl-1H9) None 3 58 i 4 66 i 6 8 i 3 HIV seonegative 21 53 1 l 59 1 2 S t l P<°-001 HIV seroposicive 30 48 1 l 76 1 2 28 i 2 Optimal ADCC activity was exhibited at serum dilutions from 1:10 to 1:100, but were seen in some sera at dilutions of 1:10.000. ADCC was reduced by prior absorption of HIV seropositive serum with HIV infected H9 cells or staph protein A. This assay demonstrates the presence of antibodies in persons infected with HIV capable of mediating ADCC in vitgo. These findings may provide further insights into the immune response to HIV, and aid in the identification of immunogenic epitopes of HIV. VVR105 Reduced Lymphocyte Cap Formation in Patients with Acquired Immunodeficiency Syndrome (AIDS) and AIDS Related Complexes (ARC GEORGEANN C. BARON, L.Y.W. BOURGUIGNON, N.G. KLIMAS, MA. FISCHL, G.B. SCOTT, and MJL FLETCHER, Univ. of Miami School of Medicine, Miami, FL, USA. Isolated mononuclear cells (MNC) from 16 adult and 6 children with AIDS, 13 adults with ARC, and 12 adult controls were examined for the ability to cap (aggregation of receptor bound fluorescein conjugated Concanavalin A (Fl-Con A) to one pole of the cell). Cap formation was scored by enumerating fluorescent caps on 200 MNC. Mean %Fl-Con A caps on MNC from the AIDS 0: ARC patients was significantly reduced when compared to that on MNC from normal controls (27% reduction in capping in adult AIDS patients, 53% reduction in capping in the children with AIDS, and 30% reduction in capping in ARC patients, p=.flalL Patchy and/or punctate fluorescent patterns were observed on the surface of MNC from the AIDS and ARC patients, while crescent shaped caps were seen on MNC from controls. Similar abnormal patterns were present when fluorescein conjugated mononclonal antibody to CD16 was used for capping on large granular lymphocytes (LCD isolated from AIDS patients, while LGL from controls formed normal caps with anti-C016. Normal capping was observed on MNC of 4 adult AIDS/KS patients and 2 adult ARC patients who were receiving in vivo human lymphoblastoid interferon (Wellferon) and bovine thymic peptides (Thymostimulin) therapy respectively. Two of the AIDS/KS were in complete remission. Capping of MNC correlated with the diminished responses to plant mitogens, CD4+ cells, decreased CD4/CD8 ratio, and subnormal natural killer cell cytotoxicity expressed on a per effector cell basis) which was observed in these patients (9:.03. The consistent reduction in receptor capping on MNC seen suggests lymphocyte membrane and cytoskeletal abnormalities in patients with HIV infections which may be related to functional defects in these cells. WEDNESDAY, JUNE 3 wR106 Natural Killer Cell Activity Against HIV Infected U937 Cells in Homosexual Men G. RAPPOCCIOLO, P. PIAZZA. Q. CAI, P. GUPTA, D. LYTER, CHARLES RINALDO, Multicenter AIDS Cohort Study, Univ. of Pittsburgh, Pittsburgh, PA 15261 Peripheral blood mononuclear leukocytes from homosexual men and heterosexual controls were testeglfor natural killer (NK) cell activity against HIV—infect- ed U937 cells in a Cr—release assay. HIV seropositive homosexual men were divided based on duration of infection: group 1, documented time after sero- conversion, 12—25 mo; group 2, estimated time of infection, 27 to 43 mo. All group 1 and group 2 subjects were asymptomatic or had persistent lymphoadeno- pathy at the time of study. Five non-MACS patients with overt AIDS (PCP) were also studied. Lysis of Uninfected and HIV Infected U937 Cells Heterosexual Homosexual Male Donors Target HIV- HIV- HIV+IGRP l HIV+/GRP 2 HIV+/AIDS U937 3923 361 202 19x sz U937+HIV slzb 41% 341 241 71 (8/8) (12/14) (6/7) (6/10) (1/5) aMean Z specific lysis (50:1, Effector:Target) DNumber of subject: showing greater lysis of HIV infected than uninfected U937 cells The results show for the first time that HIV-specific natural killer cell activity can be detected in both HIV seronegative and HIV seropositive subjects and is impaired in association with longer duration of infection and presence of AIDS. This test may be useful in evaluation of efficacy of antiviral and immunomodulatory treatment of HIV infection. Positive Cellular Immune Responses in Humans and Chimpanzees Infected with the Human Immunodeficiency Virus (HIV).JORG ELEICHBERG*,G.R.DREESMAN*,R.N.BOSWELL**, mJ. ALTER***, J.A. LEVY****, P.W. BERMAN*****, et a1" *Southwest Foundation for Biomedical Research, San Antonio, Texas; **Wi1ford Hall, San Antonio, Texas; ***NIH, Washington, D.Cd ****University of California, San Francisco, California; *****Genentech, San Francisco, California. WE107 Only a few reports have been published describing the lack of specific cell—mediated immunity (CHI) to HIV. While this lack of CHI is understandable in patients with advanced disease, it is surprising in people that are only antibody positive without concomitant disease We have assayed in a specific CHI assay mononuclear cells from humans that are anti-HIV positive without disease and compared them with chimpanzees that have been infected with either HTLV-III or ARV. All of the animals did not demonstrate any disease and have normal immune functions. The HIV antigens used in the assays were recombinant gp120, gphl and p24. All 11 chimpanzees, whether they were singly or repeatedly infected, responded positively (blastogenic index > 3.0) at one or several occasions to gp120 and/or gp41 and p24. Eight of 11 anti-HIV positive humans without disease also responded to either gpIZO and/or to gp41 and p24. To our knowledge this is the first report demonstrating a positive specific CMI response to recombinant HIV antigens in HIV infected humans and chimpanzees without disease. The results also suggest that the presence, magnitude or absence of specific CMI to HIV might determine the future outcome of HIV infection. Cytotoxic Factor Secreted by Human 'II-Lymrhotropic virus Type III Infected Cells *: S. POLMAR“: N. PAUL“: AND N. MIME“: Washington University: St. Louis: I'D: ”Yale University: New Haven: (71‘. The mechanisns responsible for depletion of T4 lymphoqtes by hunan T-lym- photropic virus type III (KEN-III) remain to be fully characterized. To explore the possibility that indirect effects might exist: conditioned media frun HIIAFIII infected cells were tested for cytotoxic cell—derived factors. The used measurements of cell proliferation of a murine fibroblast cell line: L929: which is sensitive to the effects of tumor necrosis factors: but non—permissive for HTLv—III replication. Significantly higher levels of cytotoxic activity were detected in peripheral blood mononuclear cell (IBID cultures from HTLV-III infected individuals than Eran uninfected controls. Furthermore: IBM from an uninfected individual were found to secrete this cytotoxic activity after infection in yitrg. This factor was secreted at levels ten—fold above that of the uninfected culture: 3—7 days after infec- tion: prior to signs of cell killing and the presence of reverse transcripr tase activity in the medium. TWO different HTLV-I infected cell lines: Hut 102 and AEH8: were found to constitutively secrete the cytotoxic factor. Upon infection with HTLV—III: both of these cell lines manifested cell killing: but no change in the level of the secreted cytotoxic factor. Thus: the cytotoxic factor may not be a mediator of T4 lymphocyte depletion: but nay be released as a result of cell killing in IBM: or as a reaction to virus replication. Che must consider a role for this cytotoxic factor in several aspects of H'JLv—III infection in m: including A113 encephalopathy and the systemic manifestations aocanpanying ARC. 'lhe specific cell type synthe- sizing this factor: its biochemical characterization: and biological signifi- cance are being investigated. WP.108 128 WP109 Immunologic Status of Patients with Chronic Progressive HIV ' Encephalomyelopathy (HIV-EM) FREDERICK P. SIEGAL*, C. LOPEZ**, P.A. FITZGERALD-BOCARSLY***, J.L. Z|T0*, R. RElFE*, T.W. CHEUNG****, et al., *Long Island Jewish Medical Center, New Hyde Park, NV, 7‘=*CDC, Atlanta, GA, ***UMDNJ, Newark, NJ, ****BS Coler Hospital, NY, NY USA. Among a cohort of subjects across the spectrum of HIV infection, we found A] in whom central nervous system (CNS) disease could not be explained by a definable opportunistic infection (0|). These subjects had dementia, central and cortical atrophy on CT/MRI scanning, myelopathy, and/or elevated CSF protein or leukocytes. Scans did not suggest mass lesions or multifocal leukoencephalopathy, except terminally in one case who developed CNS lymphoma. Sixteen had symptomatic CNS involvement that antedated any 0| or neoplasms definitive for AIDS. Twenty-five others developed HIV-EM during established AIDS. Defects in HSV-induced cellular interferon-alpha generation in vitro and numbers of circulating helper T cells, known to be predictive of systemic opportunistic infections, were also found to be closely associated with the development of CNS-0|. Most subjects with HIV-EM had profound depression of these measures of cellular immunity, but there was more heterogeneity among the group with HIV-EM than in those with CNS-0| or systemic 0|. These data suggest that HIV does not behave as an opportunistic agent for the CNS. How- ever, they do not exclude the possibility of a role for an early HIV-specific immune defect in the pathogenesis of HIV-EM. Expression of HIV-EM may be as dependent on variant viruses and other factors as on the presence of cellular immune competence. WP110 Response to Vaccination in HIV Serapositive Subjects - J.L. Rhonda D.L. Birx, D.C. Wright, J. Brundage, R.R. Redfield, and 5.§. Durke, Walter Reed, Washington, 0-6. The serologic and immunologic responses of 21 asymptomatic HIV aeropositive adults who were immunized with multiple polysaccharide, viral and protein vaccines were evaluated and compared with similarly vaccinated age, sex, and race matched HIV seronegative controls. The mean age was 24 (range 18-33) and 20/21 were male (951;. Lymphadenopathy was present in 20/21 (95%). The mean T4 count was 570/mm (201 with T4 < 400/mm ), the mean TA/TS ratio was 0.5 (802 with T4/T8 ratio < 0.8), and 5/21 (251) were anergic to skin tests. The number of subjects who responded to each vaccine is as follows: Vaccine: __M_ i A_7_ _'1‘_ __D_ No response to any vaccine HIV (N-21) 13 9 8 10 12 5 Normal (N-Zl) 21 15 13 9 10 0 M-Meningococcus C: response equals 6 fold bactericidal antibody titer rise. A4,A7 - Adenovirus 4, 7; response equals 4 fold neutralization antibody rise. T-Tetanus, D-Diptheria; response equals 4 fold IHA titer rise. The number of non r r ‘ rs to men! -l and ‘ iral vaccines, as well as the number of non-responders to all vaccines, in the HIV group was significant (P < 0.05) when compared with the normals. However, the geometric mean antibody titers of HIV infected vaccine responders did not differ significantly from normals. HIV infected vaccine nonresponders did not differ from HIV infected responders in total T4, skin tests,.tota1 serum IgG, or in vitro lymphocyte stimulation assays. These data suggest that a subset of_HTV positive asymptomatic subjects do not respond with antibody production to newly presented antigens; however, the majority do respond and produce functional antibody comparable to normals. At three months, no clinically apparent adverse reactions to vaccination were noted. VVR111 Report of an AIDS Patient with Persistent Normal T Helper/Inducer (CD4) Lymphocyte Counts JOHN L. ZIEGLER, D.J.MO0DV, D.P.STITES, J.A.LEVY, UCSF School of Medicine, San Francisco, CA 94143. We studied a 32 year old bisexual man who has had Kaposi's sarcoma since 1983. Serial virologic studies disclose persistent HIV antibodies (by immunofluorescence and immunoblot) and HIV viremia (by culture of peripheral blood mononuclear cells). Serial CD4 lymphocyte counts (by Leu-3 cytofluorography) range from 900 to 1190 per cu mm, and CD4/CUB lymphocyte subset ratios range from 1.2 to 1.7, all within the normal range for our laboratory. Lymphocyte responses to mitogens and natural killer cell activity were normal. Using a panning technique, we showed that the proliferative and IL-2 responses of isolated CD4 lymphocytes to tetanus and candida antigens were impaired. The patient‘s Kaposi's sarcoma lesions appear and regress spontaneously, and he is otherwise completely healthy. His wife and 2 year old daughter are also healthy and are free of HIV antibody. The natural history of AIDS is one of progressive immune im- pairment characterized by a steady decline of CD4 lymphocytes. This unusual patient has had AIDS for three years and produces infectious HIV. We are encouraged by the observation that his immune function remains relatively intact, except for anergy to soluble antigens, an early lesion described by others. WEDNESDAY, JUNE 3 WP112 B Lymphocyte-Cytotoxic Antibodies in AIDS and Related Conditions EMHJO L.KHOURY, lS.GREENSPAN, M.A.CONANT, R.CHABSON, M.R. GAROVOY, B.W. COLOMBE, University of California, San Francisco, CA. Lymphocyte-reactive antibodies have been described in AIDS and ARC patients and might contribute to the pathogenesis of these disorders. While most previous reports concern presumably specific T cell-reactive autoantibodies, reactivity against normal B lymphocytes has also been found. We investigated the prevalence, strength and speci- ficities of B lymphocyte-cytotoxic antibodies in AIDS and ARC patients as well as in asymptomatic individuals with we HIV serology, those considered at risk of HIV infection and controls. Sera from 6 groups of male patients/controls were studied: 1) homosexuals with AIDS and we HIV serology (n=16); 2) heterosexual IV drug users with AIDS and we HIV serology (n=10); 3) homosexuals with ARC and we HIV serology (n=10); 4) asymptomatic homosexuals with we HIV serology (n=10); 5) healthy homosexuals, -ve for HIV serology (n=l5); 6) healthy heterosexuals, -ve for HIV serology (n=6). Standard micro- cytotoxicity assays were performed with duplicate samples on a panel of B lymphocyte- enriched (280%) cells from 20 normal donors, representing all well-defined HLA-DR anti- gens and many of the recognized HLA-A,B specificities. An average reading of "5" in the 1 to 8 scoring system for the duplicates was considered a significant cytotoxic effect. We found a progressive increase in both the prevalence of lymphocytotoxic sera and the breadth of their reactivity in asymptomatic HIV-infected men, ARC and AIDS patients, compared with controls. For groups (1) through (6) respectively, results were as follows: (i) prevalence of we sera: 81.2%, 60%, 80%, 60%, 31.2% and 33%; (ii) average number of reactive cells out of the 20 in the panel: 10.8, 6.6, 6.7, 5.6, 4.6, and 3.5; (iii) average score of the we reactions: 7.2, 6.6, 6.7, 7.0, 5.9 and 5.5. Marked differences in reactivity within the cell panel displayed by most positive sera suggest that allo- reactivity may be the underlying mechanism, but no defined patterns for either class I or II HLA specificities could be identified, and platelet absorption of 16 positive sera abol- ished or significantly reduced the titers of their cytotoxicity on the same B lymphocytes. Monoclonal Antibodies Reactive to CD4 and 69120 Block HIV Induced Fusion of uninfected CD4" Lymphocytes LBWIS‘, C.G. BOSWORTH‘. B. YOFFB'. T. CHANHT. RONALD C. KBNNBD , ‘Howard Hughes Medical Institute. “Departments of Microbiology 5 Ilmnlmology and 'Virology. Baylor College of Hedicine. Houston. TX, and ‘1’Southwest Foundation of Biomedical Research, Department of Virology a Immunology, San Antonio, TX. USA. He recently reported that mixtures of HIV infected tumor target cells (H9) and uninfected CD4+ lymphocytes resulted in fusion and subsequent death of both cell types (3. Yoffe et al., PNAS in press). We have used this “Cr cytotoxicity assay to study the interaction between the CD4 mole- cule and the GPIZO envelope protein of HIV. These proteins are thought to be responsible for the initial binding of HIV and for the development of syncytia. He used monoclonal antibodies (mAbs) reactive to the GPlZO pep— tide 503—532 (Eur. J. Immunol. 16:1465. 1986) to block chromium release from HIV infected cells in the presence of CD41' uninfected lymphocytes. We found that mAbs reactive to the Leu3a determinant but not the OK'I‘4 determi— nant on the CD4 molecule could prevent cytolysis. 'Iwo mAbs reactive to the peptide 503-532 were also shown to prevent syncytia formation and cytoly» sis. He also determined whether addition of anti—CD7, CD3, or Dr mAbs could block cytolysis. No effect on fusion formation and cytotoxicity was observed. These data indicate that the critical interaction involved in syncytia formation is between the CD4 molecule and a specific region on the GPIZO molecule. This cytotoxicity assay is a valuable tool that may allow careful dissection of the requirements for HIV induced cytopathology. supported by NIH grant AI22549. WP.113 DOROTHY B. wE114 Reduced Numbers and Increased Activation of Monocytes in Patients with AIDS. ROBERT J. PETRELLA, Y. SE1, M.M. YOKOYAMA, J.G. BEKESI, Mount Sinai School of Medicine, New York, New York. We analized peripheral mononudear cells derived from 11 patients with AIDS. 12 subjects with ARC, and 10 heterosexual controls. Staining with fluorescein- conjugated LeuM3 and phycoerythrin-conjugated HLA-DR (Ia) monoclonal antibodies was carried out for immunofluorescence assay. The results indicated that in the AIDS and ARC patients there was a uniform depletion of LeuM3+ cells, or monocytes, of both the Ia- and Ia+ types. However, monocytes cultured for four days with ConA or PHA resulted a decrease in number of Ia+ cells relative to total monocytes. This observation corroborates previous reports of defects in mitogen response capabilities of antigen-presenting cells. In addition, in the fresh samples we observed an increase in the Ia-mAb binding per cell, in the 1a+ monocyte populations of the AIDS and ARC patients relative to controls. This increase of Ia-mAb binding is indicative of activation. These observa- tions, then, refute the proposed notion that cells of the mononuclear phago- cytic system in AIDS patients are deficient in Is antigen expression. Rather, they suggest that the defects in antigen-presenting function in AIDS are due to an overall depletion of presenting cells and to impaired antigenic response. The increased activation of the AIDS monocytea may arise as an adaptive response by the cells to reduced numbers and to the antigenic overload imposed on these patients' immune systems. 129 VVB115 Immunolo ical Virolo ical Correlates in the Clinical Progression of the Acquired Immunodeficiency Syndrome J. GEORGE BEKESI, J.I. WALLACE, P. MASON, J.P. ROBOZ, J.F. HOLLAND, Mount Sinai School of Medicine, New York, New York. We have been longitudinally following a cohort of 66 control, 166 prodromal and 36 AIDS subjects for 24 months. Eight cycles of serial immunological and virological testinga have been completed. All AIDS patients and 101 of 166 (69.9%) prodromal subjects were HIV(+). All heterosexual controls and 55 of 166 (30.1%) prodromal subjects were HIV(-). The following significant clinical changes have been observed: 14 of 55 (25.5%) of HIV(-) prodromals converted to HIV(+) and two of these (14.3%) further developed AIDS. Twenty-nine of 111 (26.1%) HIV(+) subjects developed AIDS, of these 11 (40.7%) died of AIDS. 0f the original 36 AIDS patients 21 (58.3%) have died. Contrarwiae the controls retained unchanged clinical, virological and immunological profile. Our data show that T ; inducer T and regulator T cell subsets are significantly ab- normal in HIV(-) prodromal subjects and progress to complete abrogation through AIDS and death. Lower lymphocyte function (PHA, PWM, SAC) is present in the HIV(-) prodromals, further reduction occurs at the conversion to HIV(+). Each further change in clinical status follows drastic reduction in T and B lympho- cyte function. The most sensitive indicators of clinical changes are: Th and its' subsets, SAC and PWM induced blastogenesis, CMI against auto and allo targets and chG positive cells as well as changes of anti-p17 and p24 anti- bodies in the sera. vvp116 The influence of HIV infection on antibody responses to influenza ' vaccines KENRA E.NE O , M.L. Clements, P. Miotti, S. Cohn, N.0daka, B.F. Polk, Johns Hopkins School of Public Health, Baltimore, MD., USA. This study was done to evaluate the effect of HIV infection on influenza vaccine responses. He studied HI antibody responses to A/Taiwan/86 (HI/N1) and A/Mississippi/85 (H3/N2) in 105 subjects 4 weeks after immunization with monovalent and trivalent vaccines containing these antigens. Study populations included HIV —, non - risk gp. (HIV-/NR, n = 16), HIV - risk gp. (HIV-HR, n=22), HIV + asymptomatic/LAS (HIV +, Asym, n=29), ARC (n=14), AIDS (n=24). The mean age of study subjects was similar in each group. Hi antibody responses (Logz) were as follows: HI/Nl H3/N2 £2. P_rg Post Diff. PL- Pgsl; Diff, HIV-, NR 2.93 8.125 5.18 2.56 7.81 5.25 HIV-, HR 4.09 8.0 3.91 3.91 7.95 4.05 H1V+, Asym 2.48 5.76 3.28 3.21 6.83 3.62 ARC 2.29 4.5 2.21 2.5 4.35 1.85 AIDS 2.88 4.21 1.33 2.79 4.38 1.58 Post vaccine antibody levels were significantly lower (p<.05) for HIV + Asym than HIV - NR and were lower (p<.05) for ARC/AIDS pts than all other groups for both H1/N1 and H3/N2. Protective levels of Ab (21:64) were attained to HI/Nl by 95% HIV-, 48% HIV+ Asym and 29% of ARC/AIDS pts. and to H3/NZ by 95% HIV-, 86% HIV + Asym and 29% ARC/AIDS pts. Serum levels of p24 HIV antigen did not increase significantly after immunization except in one subject. Patients with HIV infections respond poorly to influenza immunization but showed no evidence of increased HIV replication. Additional strategies, e.g. booster doses, amantidlne may be required for influenza prevention. VVP117 Lymphocyte Phenotype and Subset Distributions in ' HIV Seropositive and Seronegative Gay Men Enrolled in the Multicenter Aida Cohort Study (MACS). M.J. HAXDAL‘, J. Margolick**, J. Phair***, C. Rinaldo#, J. Giorgi##, A. Saah###, et. a1., *FAST Systems, Rockville, MD., **Johns Hopkins School of Medicine, Baltimore, MD., ***North- western University Medical School, Chicago, IL., #University of Pittsburgh, Pittsburgh, PA., ## University of California at Los Angeles, Los Angeles, CA., 0## National Institute of Allergy and Infectious Diseases, Bethesda, MD. Blood samples for flow cytometry studies were obtained from MACS participants in Baltimore. Based upon ELIZA results for HIV antibodies, the men were divided into 3 groups: (I) Sero- negative, (2) Seroconverters (within 18 months) and (3) Sero- positive (persistent for at least 36 months). The distribution of lymphocyte phenotypes, subsets, and activation markers in these groups was evaluated with a 36 monoclonal antibody dual color panel. Although the cD-4 population decreased upon seroconversion, certain subsets increased: activated CD-4 cells (MAb to non-polymorphic antigen on HLA-DR) and inducers of suppression (2H4 positive). The CD—S population expanded upon aeroconversion, and certain subsets increased disproportionally: activated CD-B cells (as in CD—4 above), and cells stained singly with 484 and 2H4 (many CD-8 cells stained positive for both). The number of receptors on the lymphocyte surface for DR and TQ-l/Leu-8 on both CD-4 and CD-8 cells also showed dramatic changes. WEDNESDAY, JUNE 3 VVR113 Cellular Immune Responses in HIV Infection JANIS V. QIORGI and J.L. FAHEY, UCLA School of Medicine, Los Angeles, CA. Immune alterations in functional subpopulations of T- lymphocytes have been characterized in HIV-infected individuals using in vitro tests of Tecell function and dual-color immunofluorescence analysis by flow cytometry. In contrast to the popular notion that loss of the capacity of CD4 T-lymphocytes to respond to soluble antigen is an early event after HIV infection, we found that only 10/29 individuals who had been infected with HIV for between 14 months and 6 years had evidence of depression of this functional activity. By testing the response of each person to both tetanus toxoid and Candida albicans, it was possible to distinguish generalized non- responsiveness to soluble antigens from a failure to respond to a particular antigen. Three of the men who were most profoundly deficient in the response to soluble antigen developed AIDS within 4 months. Since men with AIDS usually were deficient in this response, we propose that this T-cell dysfunction develops only as a late consequence of HIV infection. our flow cytometric studies exclude the possibility that loss of CD4 T-lymphocyte proliferative response to soluble antigens results from selective loss of the Leu8-, 434+, 2H4—, or HB-ll- subsets of CD4 cells. We propose that in conjunction with CD4 T-Iymphocyte numbers, the lymphocyte proliferative capacity to soluble antigens is an important variable for differential staging of HIV-infected individuals. These findings have relevance for immune evaluation assessment in therapeutic interventions in AIDS. WP119 Amyl-Nitrite Inhalation Alters Immune Function in Normal Volunteers ' ELIZABETH M. DAX, WILLIAM H. ADLER, JAMES E. NAGEL, BARBARA A. DORSEV, AND SERUM! H. UAFFE. National Institute on Drug Abuse and National Institute on Aging, at Francis Scott Key Medical Center, Baltimore, MD 21224 Epidemiological evidence shows an association of the incidence of Kaposi's sarcoma and nitrite use in patients with AIDS. Exposure of lymphocytes to nitrites jg vitro alters cell functions. Immune function has been examined in nitrite abusers but not after nitrite exposure in humans under controlled conditions. Six HIV negative, healthy male volunteers with limited previous nitrite use, inhaled 10 doses of amyl-nitrite (0.18-0.48 ml) over 4 days(D). The subjects were drug free for several days prior to 2 baseline tests of immune function. Blood was drawn on D 0, l, 4, and 7 following inhalation. lg vitro immune function tests included identification of lymphocyte subsets, natura killer cell activity, mitogenic activity to poke weed mitogen (PHM), PHA and Con A, and polyclonal induction of IgG and IgM synthesis. The pre-amyl-nitrite T4:T8 ratio was 1.56:0.21 which decreased to 1.3:0.13 immediately following inhalation. By D4 the ratio was l.59+0.23 and the representation of 14+ cells had risen from 44.8:1.3% to 48.3:3.3%. The T8+ cells remained constant at 36.213.81 and 33.3:4.5% over the same time. NK cells (leu 7+) doubled between baseline levels and 2nd day post—inhalation while NK cell activity showed an initial decrease then a significant increase by D4, post-inhalation. Leu 12+ cells showed an increase from 12.6 to 17.4% between 01 and D7 which corresponded to an increase in the mitogenic response to PHM by D7. Furthermore, 13 vitro IgG and IgM synthesis increased 519% and 301%, respectively, between 01 and 07. Results show a nitrite-induced, non-specific immune-stimulation which suggests that nitrites may aggravate AIDS by enhancing HIV replication or the non-specific stimulation may mask or interfere with specific inmune responses to pathogens. WR‘IZO Increased Levels in Plasma of Prostaglandin E2 (P6122) Could Account for the Abnormalities of Cellular Immune Functions in Drug Addicts with HIV Infection. EDUARDO FERNANDEZ-CRUZ, A. FERNANDEZ, C. GUTIERREZ, M. GARCIA MONTES, M. RODRI- GUEZ and J.M. ZABAY. Hospital Provincial. Complutense University. Madrid. Spain. Recent studies have demonstrated that PGEZ inhibit in a dose-dependent fashion a number of immunological functions and may exert a stimulatory effect on HIV replication in vitro. We have evaluated (over 2 years) the immunological, sero- logical and clinical conditions of 201 I.V. heroin abusers (892 seropositivity), and recently we have investigated the plasma levels of PGE2 in a group of addicts with the various manifestations of HIV infection. Plasma concentrations of bicy- clic PGEZ were determined by a radioimmunoassay (Radiochemical Centre, Amersham) in 3 groups of heroin addicts: group A (n=11) were HIV-positive, with depressed cell-mediated immunity (CHI); group B (n-lO), HIV-positive with normal CMI; and group C (n=5), HIV-negative with normal CHI. The results showed a significant increase in the levels of PGE2 in group A (436:62 pg/ml) as compared with group B (158119 ps/m1)(p 39°C was observed in 4/7 patients. Cough 6. or rhinorrhea were present in 6/7 (85.7%) patients. Tachypnea was seen in 3/7 patients. Wheezing wa noted in only 1 patient: a 3 yr old child who was known to have recurrent wheezing episoda in the past. Pulmonary infiltrates were seen on Roentgemgrapl’iic examination of 4/7 (57 a) patients. Hypoxia 5 mainly dishes developed soon after admision in 2 patients. One required 0.5 F102 with CPAP of 5 cm of H20 & the other 0.35 Fioz & ventillaborysupportfor hypercarbia. Oxygen requirement remained unchanged despite ribavirin aerosol therapy. On the 8th day of hospitalization Emu & Lam were detected in the tracheal lavage siecimens of one patient. On the 11th day of hoqfitalizadon, Ram was isolated from endotracheal secretiors of the other patient and it was also isolated from the lung time postmortem Both these patients died dance appropriate antibacteriaLantiviral G antiprotozoan treatment. We treated HIV infected patients below 2 yrs with Ribavin‘n s. the 2 patients above 2 yrs of age were not created. Mortality in the42, 38—42, 36-38, (36 median survival 1120. 848, 568,and 226 days. Similarly for ESR <15, 15-25, 25-50, )50 median survival was 1102, 672, 527, and #22 days H/S ratios (.3. .3-.7,>,7 median survival was 1102,1035,463. when Hot, or ESR, or H/S ratios were considered simultaneously with 35x in Cox regression, BSx were no longer statistically significant. Thus the laboratory abnormalities were more closely linked to prognosis than clinical symptoms This stduy supports the collection of baseline routine laboratory studies to estimate prognosis of newly diagnosed AIDS KS and in selecting candidates for experimental protocols. For 135 WP151 Correlation of Specific Antibodies anti HTbV-III Proteins with the Clinical Status. OLIVIERO E. VARNIER', F. LILLO', G.C. SCHITO‘. A. LAZZARIN". H. MORONI", C. LANE*‘*, et a1., 'Institute of Microbiology. Genova, Italy; nClinic of Infectious Diseases. Mllano, Italy, **‘NIAI, Bethesda. USA The aim of this study was the analysis of the immune response proteins of HTLV-III in AIDS patients to determine whether immunoreactivity correlates with the clinical status. Among the 24 AIDS patients positive for antibodies to proteins coded by both gag and env HTLV—III genes, 15 are alive. Three of the remaining 9 patients died accidently. All the last 6 AIDS dead patients had neurologlc diseases associated with the HTLV-III infection. 13 patients had antibodies directed only against the env encoded proteins and they are all dead. with the exception of one addict, who had an episode of PCP in September 1963. HTLV—III related neurologic disease was present in only 1 dead patient. Sequential serum samples of the same AIDS patient showed decreasing amounts of anti-gag antibodies and/or their disappearance in relation to disease progression or next to the exitus. Progression of the disease seems to be associated with the presence of lower levels of anti gag-protein antibodies and later on with their disappearance. If patients survive for a relatively long period of time and develop the full blown AIDS, their antibody profile is caracterized by an unique reactivity for the gpdl. Severe or unrecognized opportunistic infections, neurologlc diseases or unrelated complications will shorten the survival. Moreover, clinical improvement seems to be followed up by the recovery of the immunoreactivlty for the gag-encoded antigens. to the the WR152 Evaluation of the Gen-Probelm] Rapid Diagnostic System for the Mycobacterium Avium Complex Using Isolates from Patients with the Acquired Immunodeficienc Syndrome. John F. Keiser‘, r. Witebsky * n. Hirschmsnn‘, p. Wilkinson“, J. Brisker” and R. Aquilante****, et al. The George Hashington University Medical Center, Vashington, oc, *‘win Bethesda, MD. ‘**wa1tez Reed Army Medical Center, Washington, DC and * HGen-Probe Corporation, San Diego, CA. A new 20 test product, Gen-Probe[TH] Rapid System for the Hzcobacterium avium complex, has been introduced using nucleic acid hybridization tech- nology. Seventy-Eight isolates, identified by conventional methods, from an equal number of patients were analyzed according to the manufacture's specifications. The specimens included: 38 blood, 15 tissue, 2 stool, IO Bronchial lavage, 10 bone marrow, l CSF, l urine, and l sputum. Of the lg isolates, 72 were determined to be Hycobacterium svlum and 5 were Mycobac— terium intracellulare. The percent hybridization for 71 of the !; avium isolates showed a mean of 54 percent with a range from 55 - 91 percent. One g; avium isolate gave a 29 percent hybridization with the g; avium probe and a 9.7 percent hybridization with the !; intracellulare probe. The !; intracellulsre isolates showed a mean of 54 percent hybridization with a range from 36-60 percent. One stool isolate gave low hybridization levels with each probe due to bacterial contamination. For cost considerations, isolates should be tested first with the !; avium probe; and if negative, followed by the E; intracellulare probe. From our studies, 77I¥ 178 g; avium complex isolates gave unambiguous results. The Gen-Probe test systems shows promise as a rapid diagnostic technique. Further studies are in progress to determine specificity and clinical relevance. n* wP153 FETAL AIDS SYNDFDME: LACK OF CCRRELATION WI’ll-I MATERNAL DRUG USE. Robert W. Marion, Andrew A. Wiznia, Kirin Shah, Arye Rubinstein; Departments of Pediatrics, Microbiology and Immunology, Albert Einstein College of Medicine; Bronx, New York. The fetal AIDS syndrome (PAS) is a recognizable pattern of growth and craniofacial dysnorphic features that occurs in HIV—infected infants and children. Since the majority of these infants are born to wonen who are intravenous drug users, it is important to distinguish the features of FAS from those caused by fetal exposure to drugs. In an attempt to do this, 12 HIV-antibody positive children under the age of 2 1/2 years were examined by one of us who was blinded to the mothers' history of drug use. Using the criteria of the FAS scoring system, the subjects were divided into 3 groups: (1) severely stigmatized; (2) moderately stigmatized; (3) mildly or not stigmatized. Seven of the subjects were offspring of confirned maternal drug users; of these, 3 were severely stignatized, 3 were moderately stigmatized and I fell into the not stigmatized category. Five subjects were born to women who had become infected through heterosexual contact; 2 scored in the severely stigmatized category, 2 were judged to be moderately stignetized and l was not stignatized. when these data were analyzed, no differences in FAS score between the etiology groups could be identified. Although this study population is small, these preliminary findings suggest that FAS occurs independent of fetal drug exposure and that the features are related to infection with HIV during the first trimester of intra- uterine life. WEDNESDAY, JUNE 3 WP'154 Multifocal Cytomegalovirus Brain Infection in AIDS: Early Detection with Magnetic Resonance Imaging and Treatment with 9-(2-hydroxy-l— (hydroxymethyl)ethoxymethyl) guanine . J.C. Masdeu*, Catherine Butkus Small*, L. Weiss*, C.M. Elkin*, J. Llena*, R. Mesa-Tejadafi”, *North Central Bronx-Montefiore Hospitals, Albert Einstein College of Medicine, Bronx, N.Y., **College of Physicians and Surgeons, Columbia University, New York, N.Y. A I«3-year-old man with AIDS had clinical evidence of multifocal disease of the brain; however, computed tomography (CT) was negative. Magnetic resonance imaging (MRI) revealed multilocal lesions, proven to be caused by cytomegalovirus (CMV) by brain biopsy. CMV encephalitis was documented by light and electron microscopy as well as by immunohistochemical staining of the biopsy specimen. CMV viremia was confirmed by a positive urine culture. Therapy with 9-(2-hydroxy-l-(hydroxymethyl) ethoxymethyl) guanine (BW B759U) resulted in stabilization of the patient's clinical disease and radiographic improvement of the multifocal lesions. In AIDS patients, multifocal brain lesions on CT or MRI are seldom due to CMV, but this diagnosis must be considered in the differential. MRI is currently the procedure of choice for detecting these central nervous system lesions. Early brain biopsy is warranted, since CMV encephalitis is a potentially treatable infection. WE155 Gestational Characterstics and Bode of Delivery of 98 Children with AIDS in New York City. PAULINE A. THOMAS. R. E. O'DONNELL, P. GUIGLI, C. BROWN, J. LEE, S. SCHULTZ, New York City Department of Health, New York, NY. It has been established that Human Immunodeficiency Virus (HIV) can be transmitted from infected mothers to their offspring, probably in—utero. but the possibility of intrapartum transmission has not been disproved. If it occurs, Caesarian section (CS) delivery might be protective. we examined birth certificate records of 98 children reported with maternally transmitted AIDS in New York City (NYC) born between 1977 and 1986, and all children born in NYC during the year 1983, to assess CS delivery rates and other characteristics including birthweight. Of the 98, 71 (72%) had anthers who used intravenous narcotics (IVDU). Eleven of 62 (18%) black, 5 of 26 (191) hispanic, and one of 10 (10%) white infants with AIDS had been born by CS compared with 13% of 33,495 black, 20.51 of 31,083 hispanic and 25% of 32,787 white infants born in 1983. Differences were not statistically significant. Children who subsequently developed AIDS were more likely than the general cohort to be underweight at birth: 39% of blacks, 381 of hispanics, and 401 of whites under 2500 grams, vs. 12% of all black, 81 of all hispanic, and 4% of all white births. of infants with AIDS born to IVDU mothers, #41 were under 2500 gms vs. 33% of 8A3 infants with maternal narcotics listed on the birth certificate. Further matching by sociodemographic characteristics may lessen this difference. Prospective studies comparing infected and uninfected pregnant women will further elucidate the effect of HIV on fetal growth. Since the CS rate for delivery of infants who later developed AIDS was not lower than the rate for the general cohort, our data indicate no protection from C—section delivery. WR156 Corebrospinal Fluid (CSF) Findings in HIV Positive Patients (pts) without AIDS. MARK E. APPLEMAN, R.L BREY, D.W. MARSHALL, R.N. BOSWELL, R.W. HOUK, R.E. WINN. Wilford Hall USAF Medical Center, Lackland AFB, TX. Lumbar punctures were done on 114 consecutive pts. without AIDS evaluated for a positive HIV by Western blot. Fifty—seven pts. had normal CSF (grp I). Forty-four pts (38.6%) had abnormal (abnl) CSF (grp 11), defined as: protein _ 50 gag nucleated cells (N.C.) Z 7; or, protein Z 60 alone; or, N.C.Z 10 alone; or an elevated CSF IgG or IgG synthesis rate or the presence of oliqoclonal bands {OCH}. Grp III (57 pts) included all grp II pts plus 13 other pts meeting the standard criteria for abnl CSF: protein > 45 or NC > 5. No significant differences existed between grps for age, sex, race, 5e PTA, Walter Reed classification, CD count, or CMV, toxoplasma or EBV serolsgies. Grp III CSF findings revealed227 pts with protein > 45 {range 22- 104); 36 pts with > 5 NC (range 0-35); mean differential 0.3% polys, 90.7% lymphs, 9% others. Bacterial, fungal and AFB cultures were negative. Thirty- one pts in grp II (72%) had an elevated CSF IgG, IgG synthesis rate or 053. No significant neurologic abnormalities could definitely be attributed to these CSF findings. Head CT scans on 33 pts in grp II were abnl in 3, one of whom had an abnl MRI. This study demonstrates that significantly abnl CSF is present in about 33% of pts with HIV infections without AIDS. Follow- up of these pts will clarify the significance of these findings and their re ationship to HIV CNS infection. 136 VVP157 A Prospective Study of Human Immunodeficiency Virus (HIV) Infection in Pregnancy. H.HINKOFF, M.CABBAD, H.HENDEZ, S.HOLHAN, ANN HILLOUGHBY S.LANDESMAN, et al., SUN! Health Science Center, Brooklyn, NY & National Cancer Institute. Between 1/15/86 and 11/15/86, 278 pregnant women, including 67 Drug Addicts (IVDA), 195 Haitians and 16 sexual partners of risk members were offered HIV testing. Seventy-seven percent (215) agreed to testing. Forty-three percent of the IVDA's (N=20), 51 of the Haitians (N=8). and "31 Of the sexual partners (N=8) were confirmed seroposltive. Eight women were notified of their seroposltive status prior to 2” weeks of pregnancy; only one woman elected abortion. To date 57 women, (2“ positive and 33 negative) have delivered. Among IVDA': 2/20 negative patients had preterm deliveries compared to 6/17 positive patients. The average birthweight among :eropositive IVDA's was 2579 vs. 2899 for seronegative patients. Among Haitians, all had term deliveries with the mean birthweight 3,310 in seropositive mothers and 3,“?0 1n seronegative. There was no significant difference in the cesarean section rate. Among positive patients two had syphillis, two had hepatitis and one had amoebiasis. Among seronegatlves two had UTI's and four had parasites. All children of seroposltlve mothers demonstrated at least passive seroposltivity at birth while no children of seronegative women had antib0dy. Fallow-up studies of children is ongoing. Seroposltivity is often found among asymptomatic parturients from risk groups and may impact on birthweights. wn158 Multimodality Evoked Potentials Studies In AIDS, S.M. VISHNUBHAKAT, M.KAPLAN, R.BERESFORD, B.FARBER, T.FLYNN, North Shore University Hospital, Manhasset, N.Y., U.S.A. HIV induced central nervous system disease (CNS) has been largely studied neuroradiologically and clinically without electrophyslologic studies which may indicate pathology in asymptomatic areas of CNS. We studied 35 patients (18 homosexuals, 15 addicts, 2 others, 30 males, 5 females, 30 AIDS, and 5 AIDS re- lated complex) with visual, auditory, and somatosensory evoked responses in or— der to determine incidence, pattern, and extent of central conduction abnormal— ities. These studies were performed using Seigen clinical average: with compute facilities. Stimuli were delivered by pattern shift television screen for visud evoked response (VER), 100 decibal clicks for brainstem auditory evoked respons (BAER), median nerve stimulation for somatosensory evoked response (SSER). Thin teen patients showed abnormalities in one or two of the three modalities studid Five patients had VER and five had SSER abnormalities whereas 7 patients showed abnormalities in BAER. Five patients had VEP abnormalities, 3 had bilateral, 2 had unilateral prechiasmatic delay. None had significant visual symptoms, thoug visual acuity was abnormal in three. Five patients had SEP abnormalities, 3 had peripheral delay suggesting neuropathy, and 2 had cervical delays suggesting myelopathy affecting posterior columns. Seven patients showed BAER abnormalitie 6 had delay involving pontine pathways, whereas one had peripheral delay suggesting auditory nerve involvement. Clinical evaluation failed to reveal significant neurologic signs indicative of the abnormality revealed by EP studies. There was no correlation between EP abnormalities and staging of AIDS. Eight of the thirteen patients showed presence of peripheral neuropathy in an— other study. kle conclude that approximately 362 patients with AIDS will reveal abnormalities in multimodality evoked response study and indicate presence of CNS pathway abnormalities in largely asymptomatic areas. WP159 Clinical and Electrophysiological Features of Neuropachy in AIDS ' . MHN BHAKAT, M. KAPLAN, H. R. BERESFORD, NSUH, Manhasset, N. Y., U. S. A. Peripheral neuropathy is a known complication of AIDS. Its incidence and electrophysiologic features have not been established fully. We studied 35 patients with sensory motor latency, amplitude, conduction velocity, and long latency determination, and electromyography. These studies were performed using TECA 4 machine with photographic recording for analysis of electroneurogram and myogram. There were 18 homosexuals. 12 addicts, 3 addict wives, l secondary to transfusion, and 1 with no known risk factors. Thirty-one were male and 13 were symptomatic with predominantly peripheral symptoms of tingling and numbness in 9 and focal neuropathic symptoms in A. One patient complained of proximal weak- ness. Neurological evaluation confirmed features of neuropathy in 14 patients and consisted of mild distal sensory loss in 12, and mononeuropathy in 2. TWenty—eight patients had opportunistic infections from AIDS, and five were classified as suffering from AIDS related complex. Electrophysiologic Studies: Two of the 33 patient had carpal tunnel syndrome and 3 had mononeuropathy associated with peripheral neuropathy. Eighteen patients had symmetric peripheral sensory motor neuropathy without any evidence of either proximal neuropathy or radiculopathy. Seven of these patients showed mild to moderate distal sensory neuropathy and 11 had mixed distal sensory motor neuropathy. No instance of pure motor neuropathy was seen. Three of the 18 patients showed features of axonal neuropathy, whereas 15 had mixed features of both axonal and demyelinating type. One of the 10 patients who had normal electroneurography revealed EMG evidence of proximal myopathy. We conclude that careful EP studies will reveal significantly higher in— cidence of peripheral neuropathy in AIDS and related complex than currently be- lieved. We postulate variable etiologic factors based on the above studies. WEDNESDAY, JUNE 3 “"2160 Pituitary gland involvement in AIDS : a 57-case pathological study. ADRIEN G. SAIMOT, C. MARCHE, R. MAYORGA, P.M. GIRARD, J.L. VILDE, C. KATLAMA et al., Hopital Claude Bernard, 75019 Paris, France. Autopsy reports in 128 cases of AIDS were examined. Fifty— seven cases included a pathological study of the pituitary gland. In 44 of them (77%) no lesion was found. In 13 cases (23%) major lesions were present : 9 infections and 4 vascular anomalies. Among the 9 infections, 5 were due to cytomegalovirus (CMV), 2 to cryptococcus sp., 1 to toxoplasma gondii, l to M. tuberculOSis. Vascular anomalies were coagulation and ischemic necrosis (2) or micro-thrombosis of the neuro- hypophysis vessels (2). The 5 patients with CMV had disseminated infection (;a 3 organs), conversely in 20 patients with disseminated CMV infec— tion 15 had a normal pituitary gland. Both patients with cryp- tococcal infection of pituitary gland also had meningeal and disseminated crytptococcosis. Patients with tuberculosis and toxoplasmosis of pituitary gland also had cerebral and dissemi- nated disease. All patients had multiple opportunistic infec- tions involving organs other than pituitary gland (> 2). Signs and symptoms of hypophyseal dysfunction were not noted due to the end-stage clinical status. These findings suggest that hypophyseal function be investigated carefully at an earlier stage of AIDS. has to WR161 H_IV Infection: Unusual Viral Necrotic Skin Lesions MARCO CUSINI, R. ZERBONI, S. CAVICCHIMI, E. EERII, E. ALESSI — lst Clinic of Derma— tology — AIDS Screening Centre — University of Milan - Via Pace 9 e 20122 Milan IYALV Herpetic virus skin lesions can often have peculiar clinical aspects in AIDS patients because of immunedeficiency: chronic perianal ulcerative Herpes simplex, maculo—papular or vescico—bullo— us Cytomegalo—virus lesions have been described. In September 1936, 2 young males were admitted to our department, the first suffering from con- dylomata, the second from Kaposi‘s Sarcoma and Disseminated Holluscum Contagiosum. Ihey were both HIV infected and they had already suffered from Pneumocystis carinii pneumonia in 1986. Me Here striken by some unusual cutaneous necrotic lesions on the trunk and limbs of both patients. The lesions were few (about 10 per patient), b—lflmm in diaoeter, monomorphous, not»painful, round—shaped. The centre of the lesions was filled with a dark crust. Only sole of them showed a slightly elevated erithemato—vescicular border. At histological examination the epidermis and the dermis uere necrotic and a multilocular vescicle with some degenerating balloon cells was seen at the border of the central necrotic area. A herpes virus family infection was suspected and ultrastructural, cultural and imnunohistoche— mical examinations were performed. Culture was negative but at the electron microscopy numerous viral particles, approximately 100 nanometers in diameter. with a icosahedral nucleocapside were seen in the higher layer of epidermis both in the nucleus and in the cytoplasm of keratinocytes. Both patients were treated by intravenous aciclovir with only a slight and transitory improvement of the lesions. He think that this kind of lesion could be a neu expression of a herpetic virus cutaneous disease. WR162 Correlation between Number of T-helper (Th) Cells, Lymphocyte Re— sponse to Pokeweed Mitogen (PWM) and HIV Antigenemia in Seropositive Homosexual Males BJARNE 0.LINDHARDT*, B.HOFMANN**, K.ULRICH*, tute, **Rigshospitalet, Copenhagen, Denmark. During the clinical deterioration of HIV infected persons from a healthy carrier state to AIDS, the number of T-helper cells as well as the lymphocyte response to mitogens frequently declines. Further, it has recently been observed that HIV antigenemis is more frequent among HIV infected individuals with symptoms than those without symptoms. In order to test the possible connection between HIV antigenemia and abnormal immunological parameters, ir- respective of the clinical condition, we used a sandwich ELISA to test for HIV antigenemia in 160 seropositive homosexual males with and without immunological abnormalities. Serum and lymphocytes were drawn at the same occasion. The in— vestigated subjects were separated in 4 groups, comprising 1) 40 persons with Th-cells >500/uL and PWM-response > 202 of normal controls, 2) 40 with Th-cells >500/uL and PWM-response (202, 3) 50 with Th-cells<500/uLand PWM-response >20Z, and 4) 40 with Th-cells <500/pL and PWM-response (20%. The prevalences of HIV antigenemia found were in group group 2) 52, group 3) 13%, and group 4) 232. The differences bet- ween group 1 and 4 were statistically significant (p<0.05). Thus, it seems as if the presence of circulating HIV antigen is associa- ted rather with the viral induced decay of Th-cells than with the functional capabilities of these. *The Fibiger Insti- 1) 5%, 137 ' WE164 WE163 Observations following Splenectomy for HIV Associated I’l'P CHRIS TSOUKAS, H. STRAWCZYNSKI, R.T. CARD, G. GROWE, J. SHUSTER, P. GOLD. National Hemophilia Study, McGill University, Montreal, Canada. Immune Thrombocytopenic Purpura (ITP) is a major hematologic abnormality among hemophiliacs infected with the human immunodeficiency virus (HIV). Splenectomy is known to have a long lasting beneficial effect on resolving ITP but has been associated with an increased incidence of bacterial sepsis. To determine the effect of splenectomy on the immune system of hemophiliacs, 10 splenectomized hemophiliacs were studied, (6 before and sequentially after surgery for up to 5 years.) All patients had some findings directly related to HIV infection is. fever, fatigue, night sweats, weight loss and generalized lymphadenopathy which resolved following splenectomy. Concurrent to this sustained clinical improvement we noted a dramatic increase in platelets, lymphocytes and T cells. Pre—Splenectomy Post-Splenectomy u . 6 (mean i SD) months postoperatively (109/1.) 6 12 18 Platelets 38:11 383t96 323t34 4191149 Total Lymphocytes 2.83t2.77 5.3922.24 5.9611.39 4.98:1.09 Leu 2 (Suppressors) .38£.23 2.7222.19 2.2721.25 2.11:.86 Leu 3 (Helpers) .A3i.12 .931.3 1.442.35 1.24t.54 Leu 4 (Total T cells) .67t.26 3.29il.53 3.86:1.27 3.55t.75 One patient died siddenly 3 years after splenectomy from pneumococcal sepsis. We conclude that splenectomy in this group is an effective treatment of HIV related ITP. Although it is associated with a risk of overwhelming sepsis an overall improvement in clinical status with respect to HIV is also noted. The importance of the sustained increase in T cells and relationship to possible changes in immune function remains rn be determined. Aerosol and gallium scans in HIV infected patients with normal chest X-rays and pneumocystis carinii pneumonia. C. PICARD, J. R0550, M. MEICNAN, C. MAYAUD, J. REVUZ, A. SOBEL. Services de medecine nucléaire et de pneumologic, H6p. Henri Mondor (Créteil), Hop. Tenon (Paris), France. In 60 HIV infected patients suspected of pneumocystis carinii pneumonia (PCP), we performed graded gallium scans and measurements of alveolar permea- bility with 99mTcDTPA aerosol clearance before the bronchoalveolar lavage (BAL). Nineteen patients had proven PCP and were non smoking and non drug addicted. They were selected for this study. Seven of them had normal chest X-rays. Nine had normal PaOZ (9614.8 SD mmHg). Eleven were followed by repeated scanning after treatment. Gallium scan is positive in 13/19 patients and 99mTcDTPA clearance in 19/19 (5.41:1.7%.min-1,p 0.001 versus control 1.1:0.3u%.min-1,n=10) suggesting an increase of the permeability. Gallium scan is positive in 3/7 patients with normal chest X-rays, two having hypoxe— mla. By contrast 99mTcDTPA scan was always positive in these 7 patients even when PaOZ is normal. Their mean clearance was 6.22:1.97%.min¥1, the lower value being 3.2%.min-1 i.e. three times the normal. Under treatmenm 7/11 patients normalized both tests. Four normalized gallium but not clearan- ces : one died from extrapulmonary disease ; in the others, BAL demonstrated 1)cryptococcus, 2) pneumocystls, 3) high lymphocytosis without opportunistic infection. Gallium scan can detect PCP when chest X-rays is normal but failed in this study in 4/7 cases which were all detected by DTPA clearances measurement. This test cheaper than gallium scan is highly sensitive (100%) of PCP and normalized with recovery. Since the results are obtained in less than an hour contrasting to he hours for gallium scans, this test could be used to decide BAL in patients with suspected PCP, normal chest X—rays or blood gases. VVP165 Prognostic value of laboratory parameters in the ' clinical course of HIV-infection J.R. BDGNER, F.-D. GOEBEL, U. KRUNAWITTER, S. KELLER; Medizinische Poliklinik, University of Munich, West Germany The rate of deterioration in the clinical course and the factors for the individual prognosis of patients with HIV - infection remain to be determined. In 100 Patients Neopterin (Np), Beta—Z-Microglobulin (02), immunoglobulin (lg), platelets (Ptl), leukocytes (NBC), lymphocytes (Ly) and the score of the skin— test (Multitest Merieux)(DCH) were measured and related to the clinical stage in the Walter Reed classification (HR). After a mean observation of 12.4 months 31% showed deterioration, % regression of their WR—stage. Only Np showed a significant difference between infected (NR 1) and uninfected (HR 0) persons (p=0.01). At the end of the follow up period a significant increase in all stages concerning Np (p=0.005) and lg (p:0.025), respectively a decrease of DCH (p=0.001) was observed, in contrast to the other not significantly changed variables. patients who showed deterioration in the coming observation period had significantly higher Np values (p:U.US) and lower Ptl (p=0.005) in the first examination than those who remained unchanged. So the platelet counts and Neopterin values appear to have a predictive potency for the individual prognosis of HIV-infected persons. Those WEDNESDAY, JUNE 3 WR166 Syndrome Approaches to Early and Late Outcomes in Pediatic AIDS GHENDOLYN B. SCOTT, M.T. MASTRUCCI, S.C. HUTTO, H.P. PARKS, Department of Fediatrfis, University of Miami School of Medicine, Miami,FI. A number of distinct clinical syndromes have been identified in longitudinal natural history studies of children with HIV infection. of 1102 cases of HIV infection in infants and children identified in South Florida between January 1981 and December 1986, 134 (910.31) represent perinatal infection. The remainder acquired the infection from a blood or blood product transfusion. of the 134 perinatal cases the overall mortality is 352. In infants who meet the current CDC criteria for the diagnosis of AIDS, overall mortality is 7“. An analysis of survival indicates that the majority of deaths occur in the first 2 years of life and some clinical patterns are associated with an especially poor prognosis. In our series 1/. infants developed Pneumoc stis carinii pneumonitis in the first 12 months (mean 6) with an 5'61 overall mortality. Although the overall mortality rate decreases significantly after age 2 there are several late outcomes of this infection that are associated with significant morbidity and mortality. Progressive neurologic disease has occurred in 14 children in our series with a mean age of onset of 18 months (range 1—90) and an overall mortality of 571. The development of lymphoid interstitial pneumonitis in 35 children was associated with a better prognosis. Mean age of onset was 16 mos. (range 5-35) and overall mortality was 261. A similar mortality rate, 3332 occurred in 6 children with nephrotic syndrome (mean age of onset 36 mos, range 20—61) however this syndrome has significant morbidity associated with the development of renal failure. Overall. the prognosis for children with syndromes characterized by a lymphoproliferative response to HIV (LIP and nephrotic syndrome) is better than for those with syndromes (early PCP and neurologic syndrome) associated with deficient immune responses as suggested by normal immunoglobulins, lymphopenia and a lack of lymph node enlargement. wR167 Nocardiosis in Patients with Human Immunodeficiency Virus (HIV) Infection ELENA YAMAGUCHI, R.B.UTTAMCHANDANI, K.RODRIGUEZ, G.M.DICKINSON, M.A.FISCHL, University of Miami School Of Medicine, Miami, FL. Nocardia asteroides infection has been infrequently reported in patients with HIV infection. During a 21—month period, §.asteroides infection was docu— mented in 10 patients with antibodies to HIV (ELISA). There were 9 men and 1 woman aged 21-38 years (mean=33.5). Eight were intravenous drug users. Only 1 had antecedent AIDS, but 7 of 7 tested had cutaneous anergy, and 8 of 8 Studied had decreased T4 lymphocytes. One had concomitant Pneumocystis carinii pneumonia. E.asteroides infections included pneumonia in 5, pneumonia and chest wall abscess in 1, and localized abscess of brain (1), skin (1), retroperi— toneum (1), and mediastinum (1). Mean duration of symptoms before diagnosis was 42 days (range=7—84). Seven patients were treated with sulfadiazine, 2 with trimethoprim/sulfamethoxazole, and 1 with minocycline and cycloserine. Six of 8 evaluable patients improved, but after discharge, compliance was poor and 8 patients died with clinically active disease within 2-12 months. Autop- sies in 3 patients disclosed persistent §.asteroides in all; 2 had concomitant disseminated cytomegalovirus and Mycobacterium avium—intracellulare infections. One compliant patient continues to do well 5 months after diagnosis; the other has shown clinical recurrence 3 months after presentation due to noncompliance with treatment. §.asteroides is an important opportunistic pathogen in patients with HIV in— fection and can precede or occur sumultaneously with other opportunistic infec- tions. Specific antimicrobial therapy is associated with improvement but pro- longed treatment appears to be necessary. WP168 Malaria in African Patients with ADS ' 11%le W. Am, K. MED, A. MACHER, A. mam, M. 1k W, D. cum, at al., Registry of AIDS Pathology, AFIIPMashingtm, IX: (laconic malaria is endmdc ammg adult natives of central Africa and represents a major cause of morbidity and mrtality. Acquired immity to malaria, believed to be predominantly hunoral, is prevalau: sang the powlatim of this area. We studied the clinical course and autopsy findixgs of mo black African patients who presented with mlarial infections and AIIIS. Age a Presentiflgfllaints lhbitus W @ was 1. 37 years M anorexia, weigit loss, cough cachectic H84 8.8 gIdL 316501111:—3 2. 31 years 15‘ anorexia, weight loss, malaise cachectic 191, DIA 8.0 g/dL l«DOM—3 * H34 - hepatosplexntegaly, 11A 8 diffuse lynthadmopsthy Clinical (kntse: Blood mm at presentation revealed malarial trophozoites in both patients (P. falciErun in patient 2). In patient I, malarial parasites dissappmred after antimalarial therapy but fever and anemia persisted. The patient developed bilateral miliary pulmonary infiltrates and died in respiratory failure 6 weeks following presentation. Patient 2 (HIV seropositive) was treated with chloroquine and quinine but developed progressive pulmury insufficiency and died 9 weeks following presentation. Autm Findiw: Patient 1.: Disseminated Histgplasms capfllatun var duboisii and nultifocal visceral Kaposi's sarcoma. Patient 2'. Disseminated mcardiosis, intestinal cryptoeporidiosis, cyttmegsloviral adrenalitis, am visceral Kaposi's sarcam. here were no mlarial parasites in my Organs of either patimt. Gnclusim: Despite profound inmnndeficiency and associated bacterial, fmgal and viral infections in these patients, their chronic mlarial infectiom were not overwhelnu'rg before mtimlarial therapy, and mlarial parasites were not see-I at autopsy. The absence of fulminsnt nnlaria suggests that malaria my E represent an opportunistic infection in patients with AIIS. 138 WR169 Polyclonal Polymorphic B-Cell Lymphoproliferative Disorder (PBLD) In Children with AIDS VIJAV JOSHI, S. KAUFFMAN, J. OLESKE, S. FIKRIG, E. CONNOR, T. DENNY. CHI dren 5 Hospital of New Jersey, UMD New Jersey Medical School, Newark, NJ An unusual lymphoproliferative disorder occurring in 4 children with AIDS is described. All patients satisfied the criteria for pediatric AIDS reported by us (Human Pathol 1985;16:241) and had positive HTLV-III serology. Lung, spleen, kidneys, liver GI tract and lymph nodes showed gross nodular and/or microscopic infiltrates composed of lymphocytes, plasma cells and occasional immunoblasts. Cell marker studies showed preponderance of B cells. Immuno- peroxidase stains for both Kappa and Lambda chains were positIve in the infil- trates. Vessel wall invasion was seen In the spleen and kidneys. Cellular atypia, atypical mitosis and necrosis were absent. Two of the children had high EBV titers. We have designated this lesion as polymorphic polyclonal B cell lymphoproliferative disorder (PBLD). It may be a borderline lesion and not a full-fledged malignant neoplastic process. In pediatric AIDS systemic lymphoid hyperplasla (LH) including Pulmonary LH/Lymphoid Interstitial Pneu- monitis complex reported by us (Human Pathol, 1986;17:641) and PBLD comprise the spectrum of lymphoid proliferation possibly associated with EBV. The spectrum also includes full-fledged malignant lymphoma. VVP170 The Pathology of Pediatric AIDS: A Review of 33 Cases ' VIRGINIA M. ANDERSON*, S.L. KAUFFMAN**, J.H. SHER**, S. FIKRIG**, H. LEE**, A.M. MACHER*,*Pediatric AIDS Registry, AFIP, Washington, D.C., SUNY Health Science Center at Brooklyn, Nb.U.S.A. Case summaries and pathologic material from 33 pediatric patients were reviewed. Twenty—seven complete autopsies were performed. The case mix included 2 teenagers and 22 babies under 15 months of age. All patients had failure to thrive. Seventeen patients had severe thymic atrophy and 11 had lymphadenopathy. Opportunistic infections included: candidiasis, 12 cases; Pneumocystis carinii, 10 cases; and cytomegalovirum, 9 cases. Lymphocytic interstitial pneumonitis was seen in,10 patients. Adenoviral infection was documented in 3 childrenand 3 had E. coli sepsis. Other infections included Cryptococcus neoformans, mycoplasma, Herpes simplex, mlliary M. tuberculosis and M. avium—intracellulare, B. pertussis sepsis, recurrent salmonellosis, recurrent pneumococcal meningitis of various strains, staphylococcal sepsis, and aspergjllosis. Central nervous system pathology in 14 brains included cortical atrophy, hydrocephaly, perivascular calcification, leukoencs- phalopathy, and proliferative vascular lesions. Gastrointestinal lesions included ulceration, villous atrophy, crypt necrosis, hyperplasia of Peyers patches,and cryptosporidial infestation. Other entitles included desquamative interstitial pneumonitis,' focal myocarditis, and generalized polyclonal, polymorphic B-cell proliferation. AIDS is the commonest congenital infection in the U.$.A. In contrast to adults, infants succumb to opportunistic and common childhood pathogens . The stage of destruction of lymphoid tissue varies with the duration of illness. In AIDS and other infectious diseases of infants, the earlier the onset, the more rapid the progression. wp171 Impermeability of Condoms to HIV and Inactivation of HIV by the ' Spermacide Nonoxynol-9. SUSANNE M. SCESNEY N.M. GANTZ, J.L. SULLIVAN, University of Massachusetts — _ —L Medical Center, Worcester, MA, USA. The impermeability of condoms to HIV as well as the ability of the spermacide, nonoxynol-9 to inactivate HIV was examined. Each condom tested received a hml inoculum of HIV virus (7.x106 reverse transcriptase units). The condom was then placed over the plunger of a 50 ml disposable syringe. To model intercourse, the plunger of the syringe was pushed up and down forcefully 50 times into the syringe. After 50 plunges, media containing H9 cells was drawn up into the syringe, making contact with the external surface of the condom. The cell suspension was then cultured. No virus was detected in the H9 cells by the cytoplasmic RNA dot blot assay or by assaying cell supernatants for reverse transcriptase activity after 12-25 days in culture. Nonoxynol-9 was found to be cytotoxic at a dilution greater than .0005% necessitating that the nonoxynol-9 be removed from the virus by ultracentrifugation before inoculating of H9 cells. Nonoxynol-9 was found to inactivate HIV at a final concentration between .052 and .0052. Nonoxynol-9 does not interfere with reverse transcriptass activity nor does it degrade the viral RNA as indicated by dot blot. The effectiveness of nonoxynol-9 present in a condom in inactivating HIV in the case of the damaged condom was also tested. In 8 of 12 (662) condoms, no virus was detectable 15 days after inoculating H9 cells with HIV passed through a torn nonoxynol-9 containing condom. These data suggest that condoms are impermeable to HIV and that the spermacide nonoxynol-9 can directly inactivate HIV. WEDNESDAY, JUNE 3 wP112 Changes Over Time in Anogenital Practices in a Cohort of Homosexual] bisexual Men JANE MCCUSKER*, A.M. STODDARD*, J.G. ZAPKA*, K.H. MAYER“, 3.5. AVRUNIN*, C.S. MORRISON*, et al., *University of Massachusetts/Amherst, Amherst, MA U.S.A., **Memorial Hospital and Brown University, Providence, RI, U.S.A. Detailed information on sexual practices and HIV antibody status were obtained at 6-month intervals in a cohort of initially asymptomatic homosexual/ bisexual men at a Boston community health center. Over 200 men have been followed for at least 12 months. At the 12—month visit, 26% of subjects who reported insertive anogenital contact (IAG) always used a condom, while 30% sometimes did. The percentages for their partners' condom use in receptive anogenital contact (RAG) were: always 322, and sometimes 25%. Condom use was infrequent in other practices. Condoms were used more frequently by subjects with multiple partners. Between the initial and 12 month visits, the percentage of subjects reporting IAG decreased from 702 to 6074, and RAG decreased from 651 to 531; the percentage reporting IAG who always used a condom increased from 4% to 28%, while the percentage reporting RAG who neVer had exposure to the partner's ejaculate increased from 18% to 452. In spite of this encouraging trend, 31% of HIV seropositive men reported unprotected IAG with multiple partners and 16% of HIV seronegative men reported unprotected .RAG with multiple partners at 12 months. Results of sociodemographic, attitudinal, and other determinants of unsafe anogenital contact will be presented. WR113 SEXUAL BEHAVICXJR AND comm USAGE BY WEXUAL ME! IN IN C. SWNEX, L.C. HUMRDAND P.L. SAMARASINGHE Department of Genito Urinary Medicine, Westminster Hospital, London, England. This study was performed at the Department of Genito Urinary Medicine, Westminster Hospital, London between January and March 1986. Hanosexual men practising ano—genital intercourse were asked to canplete a questionnaire on sexual behaviour and condom usage. Approximately one third of clinic attenders practised only "safe-sex" (i.e. masturbation and body rubbing) and were excluded from the study. Data will be presented on 145 men and examines :- l. The association between ano—receptive and ano—insertive sexual behaviour preference and the presence of a regular sexual partner. 2. The number of sexual partners in the previous month and the presence or absence of a regular sexual partner 3. Sexual behaviour preference and condon usage 4. HIV antibody status and condan usage 5. mration of condom usage 6. Frequency of condon splitting or bursting 7. Types of lubrication used The 28% of men who were frequent condom users were asked to try a type of sheath prunoted as being stronger than those presently available. A spermicidal gel containing nonoxynol—9 was also given as a lubricant. Data examining their acceptability and possible advantages will be presented. This study is being repeated during 1987 in order to assess changes in sexual behaviour, with particular reference to condom usage. wp174'rhe Need for Innovation to Halt AIDS among Iv Drug Abusers (IVDA) ' and Their Sexual Partners JOHN H. mm, M.D., R. CONVISER, Ph.D., New Jersey State Dept. of Health, Trenton, NJ New Jersey's AIDS population, now 5th largest in the U.s., is unique in that 62% of its cases are drug-related. Limiting the spread of AIDS in the marginal IVDA populatim has required abarflorment of traditional public health approaches and creativity in developing a wide range of unproven tion modalities. In other jurisdictions, authorities have distributed sterile needles, bleach for cleaning needles, and condone to IVDA. In New Jersey innovaticns have included hiring ex-addict street workers, distributing coupcrs for drug detoxification, and sending out n‘obile vans. IVDA are far less likely than gay persons to read about health risks; the street workers are able to warn than verbally of these risks. The coupons have bee} effective in drawing addicts into detoxification programs by gaining widespread attention and waivirg initial fees. The mobile vans constitute a proactive step by going out to places where IVDA congregate to provide than with medical examination, educatim, and AIDS counseling, rather than waiting for than to seek out attention. Dealing with a difficult population such as IVDA requires continuing imaticn. NewJerseyismwfocusingmeducatimforthesexpartiers of IVDA, seeking than out in family planning and prenatal clinics. 139 WP115 Underemphasis on Publicly-Funded Programs For Prevention of Transmission of HIV Among Gay Men and IV Drug Users. NEIL H. FLYNN', S. HARPER', S. JAIN', P. HOLLAND", L. FERNANDO“, V. BAILEY—r, et a1.** ‘Univ. of Calif. Davis, “Sacramento Blood Center, +Aquarian Effort, and ++AIDS Foundation, Sacramento, CA Government responses to the AIDS crisis have been called "too little, too late." However, with respect to preventing transmission ('1') of HIV by blood transfusion, response was vigorous and prompt. We compared resources for prevention (P) of T by transfusion to those for P of T related to high-risk gay and bisexual/IV drug (G-B/IVD) activity in 1986 in an urban area of 900,000 population. Cost of preventing transfusion—related T was $111,305” prevented (9/80,000 units were anti-HIV +, 1.6 recipients/unit, $206,000 total cost of screen- ing). In contrast only $87,920 was spent in programs for P of T among G- B/IVD, a population in which we estimate that: 1) at least 600 T occurred in 1986 and 2) a future public liability for health care costs over the next 5 years of $9,375/T, or $5.8 million total was incurred. We conclude that: 1) P of 9.3 cases of T (15$ reduction) among G-B/IVD would justify the amount spent in P programs for this g programs for G-B/IVD were funded at the same rate as programs for transfusion-related T; 2) the public liability for future medical care for G-B/IVD-related T in 1986 was much larger (66X) than the amount spent for prevention that year. The disparity between appropriate spending for prevention of transfusion related T and underfunding of programs to prevent sexual and IVD-related ’1‘ must be addressed. The programs aimed at G-B/IVDU should prevent many cases of '1‘ and be very cost-effective in View of.‘ the high cost of treating AIDS in these groups, most of it public money. WR176 Non—Anonymous HIV Antibody Testing: Results in Colorado FREDERICK C. WOLF, C. RAEVSKY, N. SPENCER, Colorado Department of Health, Denver, CO, U.S.A. In July, 1985, the Colorado Department of Health (CDH) implemented a non—anonymous testing program for HIV antibody at 10 Testing Sites (HTS). Policies included collecting patient identifiers and risk behavior information on specially designed laboratory forms. The information is not revealed to laboratory staff but available to epidemiologists for analysis and followup. Confidentiality of records is protected. Through December 1986, 10,476 tests (314.1/100,000 pop) were processed with 13.7% positive at Denver HTS (64.9% of tests), 9.8% at HTS outside Denver (19.1 % of tests) and 16.6% at non HTS providers (16.0% of tests). Most volunteered for testing due to perceived risk of infection. Only 1.7% claimed symptoms of HIV disease although 42.5% of this group were positive. Most (78.8%) tested were men with 16.1% positive compared to 2.2% positive in women. Differences in percent positive in men by sex preference were: heterosexual 4.1%, bisexual 16.1% and homosexual 27.3%. Cited risk behaviors (RB) included: 18.4% denied any RB (3.4% positive), 48.4% claimed 1 HB (14.0% positive), and 33.2% claimed multiple RD (17.4% positive). Of those listing 2 1 RB, fewer (2.4%) of women were positive than men (18.2%). Of those with only 1 RB, sexual contact with homo/bisexual men was mot frequently cited by both men (78.8%), 19.6% positive) and women (43.6%, 0.3% positive). Negatives were less likely to return for results and prevention counseling than positives (77.5% vs. 88.3%). Patient identifiers allows follow-up of positives who did not return (129), as well as evaluation of the number of persons tested (9,267), and those who seroconvert (2.1%), linkage with AIDS reports, and efficient contact referraL WP177 Prevention of HIV Infection through Sexual Behavior Change. ' JOHN L. MARTIN, Columbia U. School of Public Health, NYC, NY. Given the critical role of education and behavior change in controlling AIDS we studied the efficacy of reductions in specific sexual behaviors as means of preventing HIV infection. Data used in the analysis come from a prospective cohort study of 360 NYC gay men in which HIV serologic data and detailed sexual histories were gathered. Linear logistic regression modelling was used to pra' dict HIV antibody status as of 1986 from seven sexual activities (kissing and receptive/insertive anal intercourse, oral—genital sex, and oral—anal sex) mea- sured for each of two prior annual time periods: Pre-AIDS, 1980—1981, and post- AIDS, 1984-1985. Frequency of receptive anal intercourse during both pre-AIDS and post-AIDS periods were the only significant predictors of 1986 antibody status. The re— lationships held for all levels of number of partners. The efficacy of beha- vior change in preventing HIV infection was quantified by dividing respondents who engaged in receptive anal intercourse during the pre-AIDS period into: (1) those who stopped anal intercourse in the post-AIDS period, 1984—1985, and (ii) those who did not not stop in the post—AIDS period. Of those who stopped receptive intercourse, 222 were HIV positive as of 1986 while 48% of those who did not stop were positive (odds ratio=3.26, 95% CI l.70,6.22). This effect is stronger for the most sexually active half of the sample. Among those with 15 or more partners in the pre-AIDS year, 26% who stopped receptive intercourse were HIV positive as of 1986,while 64% of those who did not stop were positive (odds ratio=5.02, 95% CI 2.13,ll.74). These results indicate that behavior change, specifically eliminating receptive anal intercourse, can significantly reduce the likelihood of initial HIV infection among gay men. WEDNESDAY, JUNE 3 WP178 "RAP‘N Down S'I‘Ds, Drugs, and AIDS", A Conmunity-based Approach to AIDS Education Among Minority Adolescents PAUL GIBSCN‘M F. S'I‘ROUD*, L. S‘IOLLER", S. Gmss‘“, M. FULIIDVE**, K. SHINE**. *San Francisco Department of Public Health, San Francisco, CA, MBayview Hunt- ers Point Foundation, San Francisco, CA. To stimulate AIDS awareness and education for minority adolescents, we pilot— ed a cooperative conmunity project utilizing RAP music to attract minority teens to participate in a "RAP'N Down STDs, Drugs, and AIDS" contest. The goals of the project were to create a fun, non-traditional approach for minor- ity adolescents to become involved in their ohm learning about risk behaviors for AIDS and other SIDS, and to stimulate canmunity involvement and support with a highly-visible awareness campaign. The Department of Public Health contracted with a major conmunity organiza— tion to coordinate the project with 5 youth-serving agencies (YSA) . Each YSA conducted promotion and educational outreach for a neighborhood preliminary "RAP Off", planned to coincide with the 1987 Valentine's Day and National Con- dom week. The finalists from the 5 "RAP Offs" competed for the grand prize of $500 on a popular television program. To win, contestants had to compose and perform a 60-second RAP about AIDS prevention. The RAPs of the finalists were recorded and aired as public service announcements on popular radio stations. This project may serve as a model for innovative ccmnuinity—based AIDS awareness and education campaigns for special populations in other metropolitan areas. WR179 A Multi-Media Campaign to Encourage Condom Utilization CATHERINE A. HANKINS*, M. STEBEN**, B. Vigneau , D. Bonney SORMANY , 1. BLACK******, et a1., Montreal Regional Transmitted Disease Control Program, Montreal, Quebec, Canada, Health Department, Verdun Hospital, Montreal, Quebec, Canada, Community Health Department, Verdun Hospital, Montreal, Québec, Canada, Community Health Department, Montreal General Hospital, Montreal, Quebec, Canada, **** Bazin, Dumas, Dupré, Sormany, Communicateuts-Conseils, Montréal, Québec, Canada, ****** Publicité Kitching Advertising, Montreal, Quebec, Canada A multi—media campaign targetting young people aged 15 to 24 years was launched in April I987 in the province of Quebec, CANADA. The primary message of the campaign focussed on encouraging condom utilization to prevent sexually transmitted diseases. On a limited budget, television, radio and print advertising was developed to coordinate with a public relations communications plan aimed at province wide penetration. Varied support activities, including the distribution of pamphlets, flyers and posters, were conducted by local health units to coincide with the campaign. Initially, difficulties were encountered in convincing networks to carry television advertising mentionning condoms even when presented in generic form by a health organisation. Considerable public debate was engendered during both the design and the implementation phases. Pre- and post—campaign public opinion polls were conducted as one measure of the effectiveness of the intensive phase of the campaign. **** , A. Sexually Communi ty *** wp180 DRUG USERS' ORGANIZATIONS AND AIDS PREVENTION: DEPRENCES IN STRUCTURE AND STRATEGY SW w. DE JONG“, D.C. DES JARLAIS'”, C.D. KAPLAN“, D. S. GOLDSMITH“, *Narcotic and Drug Research, Inc., ”Erasmus University Rotterdam, “‘NY State Division of Substance Abuse Services Organizations of homosexual men have provided services to persons with AIDS and ARC, educated gays about risk reduction, and given gay men a voice in AIDS policy and research debates. Innavenous (IV) drug users had less fomial organization prior to the epidemic, and have been much slower to mobilize in response to AIDS. We have conducted field research on the Dutch junIdebonden (drug users' unions) and ADAPT in New York City. These drug users‘ organizations have disuibuted AJDS information to IV drug users both in person and through the mass media. Junldebonden existed before AIDS was recognized; ihey have reacted to die epidemic in different ways. They have had internal conflicts over their goals and values, and external disagreemems with public health and drug munch! agencies. They had previously initiated a system for exchanging used syringes for sterile ones, and have since taken part in the official needle exchange program, ' ' L at times . ‘ instability has ’ ‘ from their abilin to dispense syringes. ADAPT, an organization of ex-IVdrug users, cunsm IV drug users, and health professionals, was organized specifically to deal with AIDS. It has provided mining to drug treatment agency staffs, and services to individuals with AIDS or severe ARC. ADAPT and some junldzbanden have taught individual drug users ways to reduce the risk of exposure to HIV or of transmitting iI to others. On the basis of our observations, it appears that in which and health ‘ ' ' ‘ ' can provide consistent interventions which can motivate risk reduction among those dnig users who are most open to change. It also appears that organizations of hard drug users are unstable, but when they are funciioning well are more able to reach those street drug users who panicularly distrust established institutions and to develop new values among drug users that will legitimate "safe injecu'on" procedures among persons who continue to inject drugs. 140 WR181 In Vitro Tests Demonstrate Condoms Containing Nonoxymol-Q Provide Effective Physical and Chemical Barriers against Hanan Immodeficiency Virus comm fi RIED‘IEIW, JJI. KREBSH‘, P.H. 1'50le and EN. JUDSOIF, *Denver Discus Control Service and The University of Colorado, Denver, 00, "* AIDS Program. CDC, Atlanta, CA. In an in-vitro model 20 condoms (Ansell Inc., Dothan AL), 10 with 0.9 ml 6.6% (v/v) nonoxynol-9 (NX) and 10 without “K, were tested as barriers against human immodeflciency virus (HIV). Each condom was mounted on a 20 cm hollow dildo and placed in a 15 x 5 cm glass cylinder containing 10 ml of HIV—free RPHI 16“) medium. A ml of cell-free and cell-bound HIV medium was placed inside the condom tip. To simulate intercourse, the dildo was pumped up and down 100 times. Samples were taken from the media inside and outside the condom for I-EIV cultures. Next the condom was ruptured. Again intercourse was simulated and samples cultured. All experiments were repeated in the reverse fashion, Le. with HIV medium in the cylinder and HIV-free medium inside the condom tip. CONDOHS WITHOUT NX CONDOMS Hull NX HIV med ium inside ins lda inside outside Sample from outside outside inside outside pro-rupture post-rupture pro-rupture post-rupture Culture positive 0/10 7/10 0/10 0/10 Cultures were tested for HIV RT activity for 6 weeks. No condom without "x leaked HIV before rupture, but after rupture HIV could be detected in outside medium. In contrast none of the samples taken either before or after rupture of the MK containing condoms was positive. We con- clude that undamaged condoms provide an effective physical barrier against HIV and that 6.6 ’5 nonoxynoI-9 diluted < 22 times after condom rupture may provide an effective chemical barrier. WP182 (Immunity-Based Damnstratim Project for ADE Prevmtion and Risk Reduction: ' Organization of a Cowrehensive Prevention Progran in Denver. DAVID L. (11W, P.J. cum, K.R. O’REULW, F.N. W, Denver Disease Control Service 065*, Denver, a) and Centers for usesse Control (012)”, Atlanta, GA, U.S.A. b11986, D60rganizedaomprehensive reglmalAIDSpreventimpmgt-anaspartofan-spon- sored (‘annmity—Ease‘l Demnstration Project (11’) for ADS prevention and risk reduction. The main purpose of the DP is to determine the most effective mam for prevention of I-HV trans- mission in populations at risk, praominantly through educational programs. mum mdali— tia include literature, posters, audio-visual aides, lectures and serious, public service armmcamants, introduction of A115 education into public school curricula, and skills provision trairdng in populations at risk. An ADDS/HIV Infomtion Service provides educational materials and newsletters, serves as a clearing-ruse for new information, arrarges seninars, has a phone response center, and networks with other educational groups. HIV antibody testirg and mimellng and mrlal crosseectimal semprevalenoe envoys are per formed at an HIV testirg and winselirg site, SD) clirdc, IV drug me treatment centers, select- e‘l obstetric clinics, and blood barks. Populations studied ilk-Jule gay nan, IV dug users, female prostitutes, high-risk obstetric patients, heterosexuals in a SI‘D clinic, aid military recruits. In addition, a large mhort of gay inn is recruited for a prospective lotgltudinal surly to eval- uate different and Innovative educational nodalitles and to elicit utensive information about knowledge, attitudes, and beliefs cmnernirg AIIE and risk behaviors. masurements incline serLal seroprevalence studia; A118 surveillance; rates of gonorrhea, syphilis and hepatitis; and questionnaire surveys in different populations. Within the coinrt, behavioral differences between aeropositive and serunegative, and seroconvertor an! aemtegatlve subjects will be analyzed. Graduation of a mupmliersive AIDS prevention program tequila significant resources, lore term planning, well-trained personnel, adequate laboratory and office facilitla, cooperation with diverse committee and radical care providers, development of nul- tlple education mdalities, flatlblllty in “sparse to changirg needs, and arguing evaluation. The 800 Men Study: A Controlled Study Of An AIDS Prevention Program WR183 In New York City MICHAEL QUADLAND, H.D. SHATTLS, R. SCHUMAN, R. JACOBS Since 1982, traditional AIDS education programs in New York City have lmparted information about the disease and its transmission. To date there has been no systematic study of the effects of such programs on sexual attitudes orbehavlon In October of 1985, 619 gay and bisexual men participated in a controlled study of pre- and post- test experimental design to evaluate the effects on sexual attitudes and behavior of four different education programs. It was hypothe- sized that a program which attempted to eroticize safer sex would be more effective than the traditional program, that the use of explicit erotic audio- visuals would be more effective than not, and that all three interventions in which participants met in groups would be more effective than an Information- only, at-home control group. It was found that: (1) there was a substantial amount of heterosexualactlvity in the sample; (2) most participants had already made substantial changes in sexual behavior, but approximately 40% were still at risk; (3) change in atti- tudes and behavior was associated with participation In a group educational experience; (4) changes in sexual behavior were observed in both the traditional and eroticizlng programs; and, (5) the use of explicit erotic audiovisuals is more effective than not In promoting safer sexual alternatives. These findings are Important In providing a rationale for a more positive approach to AIDS prevention which includes attempts to eroticize safer sexual behavior. WEDNESDAY, JUNE 3 WR184 Consequences of AIDS Antibody Testing Among Gay Men: The AIDS Behavioral Research Project. THOMAS J. COATES, S.F. MORIN, L. MCKUSICK, University of California, San Francisco, School of Medicine. We followed 560 gay and bisexual men from November 1986 (before HIV antibody testing was available) until November 1985 and November 1986 (after HIV anti- body testing was available) to determine the consequences of such testing on high risk sexual and drug use behavior, psychological distress, and relationship status. In November 1984 there were no differences between groups ultimately testing positive and negative in percent of men reporting high risk sexual behavior. After antibody results were found out, significantly greater percentages of those who found out that they were antibody positive ceased practicing unprotected active and passive anal intercourse. Also, the antibody positive group reported significantly greater stress and depression and their relationships were more likely to break up. The results of this study indicate that antibody testing may have positive public health outcomes. However, even though positive antibody status was associated with reductions in high risk behavior in those tested, it was also associated with potentially adverse mental health consequences. We found significant increases in stress and depression in the antibody positive group. Men in the antibody positive group were also more likely to have their primary relationships break up and to be celibate. More intensive study of antibody positive persons is needed to determine the full significance of these findings particularly for long- term mental health services. WE185 Targeted Outreach Techniques for Minority AIDS Education. RACINE WINBORNE, B. M. Branson, J. Stein. D. Vaughan. Health Education Resource Organization, Baltimore, MD, USA. Disproportionate numbers of reported AIDS cases among Black Maryland res- idents prompted the development of targeted. culturally sensitive education efforts to improve AIDS awareness and prevention measures. Questionnaires indicated that certain radio stations were more likely to reach the desired population, and that print media was much less effective. A bus poster was designed to advertise an information hotline phone number; the large number of callers who identified this poster as their source of inform- ation proved this to be the single most effective technique to deliver an educational message to a large segment of the Black population in Baltimore city. Community leaders were recruited for a Minority Task Force, and Black church organizations were solicited to provide educational forums; church leaders appeared in public service announcements. Denial of the excess incidence proved to be the most significant barrier to initiating community-based educational programs. A series of educational presentations for tenants associations in the Baltimore City Housing Authority served to stimulate interest. and increase receptiveness. wP186 AIDS Antibody Testing: Who Takes the Test? STEPHEN MORIN, T.J. ' COATES, w. wooos, L. MCKUSICK, University of California, San Francisco, School of Medicine. This study presents data on reasons given by gay men for wanting to be tested for antibodies to HIV. Data were gathered in 695 gay and bisexual men in San Francisco who responded in May 1985 and 676 men who responded in November 1985, and 1986, as part of a larger ongoing longitudinal study. By November 1985 less than 31% had been tested even though anonymous and confidential test- ing had been widely available since July, 1985. The primary motivations for being tested were to reduce anxiety and uncertainty and to know if one was capable of infecting others. The primary motivations for not being tested were fears of increasing anxiety, perceptions that the test lacked meaning, and concerns about confidentiality and the potential for discrimination. Gay men in the sample were relatively well informed about AIDS and the meaning of the HIV antibody test. The respondents generally recognized that a positive test result did not necessarily mean that an individual would go on to develop a deadly form of AIDS. Most recognized that a negative antibody result could mean that the body had not yet produced antibodies to the virus and that it was possible to have the virus without antibodies. Our data suggested that the primary reasons for wanting or not wanting to be tested were psychological rather than medical Those who did not want to be tested believed that knowing that one had been infected would greatly increase one's anxiety and fear. Going through testing provokes anxiety as does living a life knowing that one has been infected with the AIDS virus. Community education efforts have resolved concerns about the meaning of the test and poor test validity. Those who did not want to be tested wanted to clear up ambiguity about past infection and to have good information so that they would avoid infecting others. 141 WP181 An AIDS Education Outreach Program for Minority Communities 99 ANN VALENTINE, Y. RIVERA, A. FREEMAN, C. HALEY, Dallas County Health Department, Dallas, TX AIDS education in minority communities must emphasize messages to reduce fear and to increase the understanding of risk behaviors and focus on behav— iors to reach persons who would not identify themselves to be in a risk group but who do engage in risky behaviors. In addition, AIDS education provided through traiitional media channels has not adequately reached minorities with— out a program that actively identifies minority communication lines and persons of influence to deliver the messages. The Dallas County Health Department has developed an active program of AIDS education outreach to the black and hispanic camnmities. The goals of the program are to identify cormnmity leaders on health issues, enlist their sup— port in planning an approach and provide the information in a setting that allows attendance without being perceived as "needing" the information. Social service organizations, cannunity councils, minority professional groups, ministers, health care providers and radio personalities have been very effective in planning educational messages and in lending their support and increasing the credibility of the messages. Minority populations have been reached in Dallas by addressing AIDS as a risk to sexual partners of IV drug users, persons with multiple partners and ado- lescents. Educational outreach has been most successful in churches, schools (after approval by parents), public housing tenants' association meetings and English as a second language classes. WR188 "AIDS as an Industrial Issue: The Australian Experience" Mgfig_fiflfl§ and ANDREW MORLET, Albion Street (AIDS) Centre, Sydney Hospital, N.S.w., Australia. The industrial issues surrounding the AIDS epidemic have yet to be fully recognised in Australia. During the past two years several of Australia's major employers have had to provide services to employees infected by HIV, and to deal with widespread ignorance and fear. The Sydney AIDS Clinic has been used as an outside consultant by several of Australia's major employers, to advise on health and policy issues relating to HIV infection. This paper, using case examples, examines the types of problems employers have experienced: denial of a problem; absence of policies on infectious diseases; hysterical staff reactions to fellow workers with HIV infection and industrial, health and welfare issues relating to the identification of infected employees. It is argued, using case examples, that industrial problems can be minimised by a) recognising AIDS as having industrial remifications — both for occupational health and safety and staff welfare; b) the development of policies related to infectious disease; c) the provision of counselling/information and in-service training; and d) use of outside consultants. the wn189 Sexual Relations in Bathhouses in Los Angeles County: Implications for AIDS Prevention Education GARY A. BICHWALD", A.R. KRISTAL**, G.R. KYLE*, D.E. M.M. GERBER*, *UCLA School of Public Health, Los Angeles, **Fred Hutchinson Cancer Research Center, Seattle, WA. 807 men at 7 bathhouses in Los Angeles County completed exit interviews in July and August of 1986. 61 percent participated in activities associated with low risk of HIV transmission, while 10% participated in passive and/or active anal intercourse without a condom, behavior associated with the highest risk of HIV transmission. In comparison, more of the high risk group were under 30 (46% vs. 34%), belonged to minority groups (41% vs. 27%), earned less than $20,000 annually (44% vs. 26%), had not attended college (24% vs. 12%), had 5 or more male sexual MORISKY*, CA, partners in the past month (46% vs. 25%), and participated in fellatio without a condom (60% vs. 20%) (all p<.05). Similar proportions reported familiarity with information in the bathhouse on AIDS (96% vs. 98%) and felt it played a role in their understanding of AIDS prevention (84% vs. 86%). These data indicate that the majority of highly sexually active men who attend bathhouses in Los Angeles County new practice low risk sexual behaviors. However, improved programs directed toward those young, minority, low income, less educated men who are at highest risk of HIV transmission must be developed as soon 1 possible. WEDNESDAY, JUNE 3 WR190 Blood Donation Histories of Reported AIDS Patients. E. THOMAS STARCHER, 11, MC NOA, Jw WARD, TJ DONDERO, Jr, J»: CURRAN- Centers for Disease Control, Atlanta, Georgia, USA Patients meeting the national case definition for AIDS are reported to CDC on standardized case—report forms that include a question on blood/plasma donations since 1978. Between March 1985, when test kits to detect antibody to HIV were licensed for screening blood, and October 31, 1986, 17,387 AIDS cases were reported to CDC. Among the 9,143 (53%) patients who answered the blood donation question, 394 (4%) gave histories of blood donation since 1978, but only 25 had donated since March 1985. Of the 25 recent donors, 23 were men; of these, 13 were bisexual, 9 were homosexual, and l was a heterosexual IV drug abuser. The 2 women were heterosexual partners of high—risk individuals (a bisexual male and an IV-drug abuser). Eighteen (722) of the recent donors were white; 5 (20%), black; and 2 (8%), Hispanic. When compared with all reported AIDS patients, those answering "yes" to the blood donation question were more likely to be white and bisexual. Since intensive screening of blood donors began in the spring of 1985, some members of high-risk groups continue to donate blood or blood products. Although still important for preventing transfusion-associated AIDS, blood donations by high-risk individuals suggests an even larger problem in the broader effort to prevent the spread of AIDS: persons who do not perceive themselves at high risk and therefore ineligible for donating blood may also not perceive the need to engage in risk—reduction behaviors. Since our data pertain only to reported AIDS cases and do not include the larger pool of HIV-infected persons without overt AIDS, the risk awareness problem may be considerably greater. A Modified System of Contract Tracing for HIV Seropositives MICHAEL L. REKART, Division of STD Control, British Columbia Mini— stry of Health, Vancouver, B.C., Canada Control strategies for sexually transmitted diseases (STD's) must be appro- priate, effective and acceptable. Both formal contact tracing, where a public health worker notifies named sexual partners, and simplified contact tracing, where the index patient does the notification, are well accepted methods of STD control. A simplified system is usually used for AIDS patients and HIV seropositives. A formal system of naming contacts to an interviewer would be unacceptable and counter—productive in HIV infections. There may be contacts, however, whom the seropositive patient wishes to be notified but will not himself notify because of inability, fear or embarass— ment. Public health officials should make themselves available to locate such contacts. This is especially important since such contacts may include persons who have no suspicion of HIV exposure, for example, female sexual partners of unacknowledged bisexuals. In British Columbia, HIV seropositives are requested to anonymously submit to STD control authorities identifying information on contacts they themselves will not notify. These sexual partners exposed to HIV are then located through the traditional public health infra—structure, notified of the exposure and offered information, counselling, antibody testing and support. This system has found acceptance and support from all groups involved in AIDS and early results are encouraging. WP.191 The National Condom Awareness Project: A National Survey of Knowledge of AIDS, Use of Condoms and Sexual Behavior Among College Adolescents RALPH J. DICLEMENTE, PhD and KATHERINE FORREST, MD, University of California, School of Medicine, Department of Epidemiology and International Health, San Francisco, CA 94143 The National Condom Awareness Project (NCAP), presently underway, is a survey assessing college-age adolescents' knowledge, attitudes and misconceptions about AIDS, use of condoms and type and frequency of sexual practices. Approximately 2,000 college undergraduates matriculating at 18 major universities geographically-distributed in the United States are participating in the project. Students complete an anonymous self—report questionnaire designed to elicit information about knowledge of AIDS: transmission, prevention and misconceptions, knowledge of other sexually transmitted diseases, attitudes regarding perceived risk of HIV infection, use of condoms, decision-making processes which influence the risk of engaging in high-risk sexual behaviors and type and frequency of sexual practices. Data will be presented describing geographic, ethnic/racial and gender differences as well as the interrelationships between knowledge of AIDS, perceived risk of HIV infection, type of sexual practices and use of condoms. The NCAP can be useful in providing baseline information on this population as well as in the planning, development and implementation of public health and college— based AIDS risk-reduction education programs for adolescents. WP.192 MPH 142 WE193 AIDS Educatlon Optlons by the 0.5- Health Insurance Industry HARVEV S- BARTNOF MD, UCSF School of Medlclne and AVERI, AIDS VIrus Educatlon and Research lnstltuto, San Francisco, CA Hlthout any known curatlve therapy or vacclnatlon for HIV lnfectlons. preventlon through educatlon wIII remuln a cornerstone tor stun-Ing the eplda-Ic. Every potentlal avenue of oducatlon needs to be explored In attempt to reach all populatlons- He hypothoslzed that the US Health Insurance Industry (HII) may have altrulstlc and flscal lncentlvos to provide AIDS sducatlon for tholr subscrlbors. A conildentlal telephone survey of 24 Hll companlos wlth otflces In the S.F. Bay Area was undertaken (I) to deter-Ina what klnd, If any, AIDS aducotlon had been provlded tor subscribers, and (2) whether or not these HII conpanles would be Interested In provldlng AIDS educatlon. Thls survey was completed prlor to the Surgeon General's or Hat'l. Inst. of Hedlclne's Reports about AIDS. Approprlnto adnlnlstrntlva oftlclals of each company were Intorvlowod by phone. All respondents Indlcatod that educatlon on transllsslon Is an Important means of prsventlon. 541 of HII companles had rocolvod or atte-ptod to recelve educatlonal materlals on AIDS. None had actually provldod Infor-atlon on AIDS to subscrlbers- 72! felt thelr subscrlbers could use more Informatlon about HIV transmlsslon. 601 tolt It was In tholr coopany's best Interest to provlde Intormatlon on AIDS transmlsslon to thelr subscrlbsrs and that provldlng such Information would lower the lncldence of HIV Infoctlons In theIr subscrlbers. These data Indlcato that a salple of the US Hll has not provlded AIDS Informatlon for thelr subscrlbsrs. but would do so to decrease the lncIdence of HIV Infectlons. AIDS oducntlon by the H11 represents a vluble means of HIV educntlon and Inplolentlng such a pollcy will decrease the spread of HIV In the US and elsewhere- wn194 Changing the Public Debate on AIDS: A Need for a Communal or Societal Approach to The Problem. SHELDON H. LANDESMAN', M.D. SUNY Health Science Center at Brooklyn*, Brooklyn, N.Y. In the absence of effective medical therapy, control of the AIDS epidemic requires the dissemination and acceptance of complex and controversial educational messages. The nature of the public debate has undermined our ability to delivery effective education to the public. Examples include (1) discussions of anal-genital intercourse as dangerous (as opposed to 3px intercourse with an infected person being dangerous), (2) comments about AIDS not being a threat to the "general population" (as if the 1.5 million infected persons are not the "general population"). Statements such as these stimulate the public's perception that AIDS is "their" (gay and drug users) problem, not "our" problem and heighten the public's sense that "they", the infected, may give the disease to "us", the healthy. It is only by emphasizing the communal nature of the AIDS threat and seeking from all members of society an increased measure of trust and sacrifice can the public debate on AIDS result in positive steps directed towards decreasing transmission. In the absence of a communal or societal View of the epidemic, the public debate will become increasingly rancorous as uninfected populations begin to feel more threatened. The result will be increasingly oppressive social legislation (mandatory reporting or testing, quarantine, etc.) put' in place as "quick fix~ solutions that are usually counterproductive to the aim of slowing transmission. Examples of such processes are already visible-six states have mandatory reporting of HIV seropositivity (an obvious disincentive for testing). A societally centered public debate is essential to avoid an acrimonious and adversarial public fight over how best to control the AIDS epidemic. WP195 Lessons of History: What Really Works in Reducing STD Rates? ' CHARLES F. CLARK, M.D., AUSTIN c. KUHN. MSW, SHAPE Hospital, Casteau. Belgium, EDMUND C. TRAMONT, M.D., Walter Reed Army Institute of Research, Washington DC. with the realization that the HIV epidemic heralds a catastrome for American society, scientific and social organizations have called for massive educational efforts costing hundreds of millions of dollars. What can we learn from past experience about the effectiveness of such programs? Because the introduction of sulfonamides and penicillin in the early 19405 so effectively treated gonorrhea and syphilis as to eliminate venereal Disease treatment as a medical specialty, the experience of controlling sexually transmitted diseases by social engineering has been lost. A massive unitary US Army program to educate and protect soldiers Eran sexually transmitted diseases was implanented in 1911. The effects of this massive program may be seen in the statistics for an) in American troops stationed in the Panama Canal Zone from 1911 to 1922. 1911-118 1913-197 1915-137 1917—124 1919— 83 1921-154 1912- 69 1914-136 1916-116 1918— 67 1920—139 1922-144 The drop in 1912 reflects confusion over the beginning of the program. The sharp drop in 1918 and 1919 reflects the takeover of the cities of the Zone by military authorities as decreed by Treaty during the time of declared war in Europe with the authorities inmediately and vigorously sumressing proaitution. The standardized education, inspection, distraction, and punislnent canpaign had no perceptible effect whereas the suppression of prwtitution had a clear and dramatic effect, but even then the rate was halved, not brought to zero. WEDNESDAY, JUNE 3 wP196 Inter- and Intra— Personal Factors in the Recruitment and Retention of Research Subjects For an AIDS Intervention Research Study SALLY DODDS*, MA. F‘LE'I‘CHER**, P. O‘HEARN'H', P. COLE‘, P. CARALIS**, et al., *Health Crisis Network, “University of Miami, Miami, FL. University AIDS researchers and staff and volunteers of a community AIDS service organization have collaborated to design and implement a multi—year study on the effects of stress, psychosocial variables and exercise on the health and immunologic status of gay men at risk for AIDS. More importantly, the study will evaluate the efficacy of exercise and stress reduction techniques as buffers of possible adverse effects of stress on health and immune function. Observation and subject reporting of the initial three groups of subjects (N=25), have revealed several inter/intrapersonal factors that have implications for the success of this type of research project with this population. Some of these factors are: that subjects move through several psychological phases including engagement, affiliation, committment and termination; that voluntary participation in the study requires that high risk men accept the realities of their risk factors, confront the anxiety related to disclosure of HIV status and immune function, develop group identity with other subjects, commit to attendance at frequent study—related appointments, and integrate new patterns of stress reduction and exercise into their lives; that substantial staff support has been necessary to adequately obtain informed consent, provide crisis counseling after disclosure of HIV positivity, encourage discussion of feelings related to behavior change, and; that subjects themselves serve to perpetuate the study by becoming spokespersons, exercise trainers and recruiters. (Supported by grant No. l P50MH42455—Dl from NIMH). wn197 "AIDS Comunity Outreach for Intravenous Drug Users" Harvey III. Feldman, Ph.D. & Patrick Biernacki, Ph.D. YES Project, 1779 Height St., San Francisco, CA 9All7. In May 1986, a community health education/outreach program was created in San Francisco to stop the spread of AIDS among intravenous drug users (IVDUs). Currently, the program employs eight workers who provide AIDS education, counseling and referral to drug users in those areas of the city that contain the highest concentrations of IVDUs. This paper describes and analyzes the major stages undergone since the program's inception and addresses problems encountered. The analysis will help other communities to develop similar outreach efforts. The program developed in the following stages: 1) Formation of the overall strategy guiding the program effort toward the major goal of stopping the spread of AIDS among IVDUs; 2) Ethnographic studies of target areas to map out & analyze the needle-using scenes and drug-using practices; 3) Recruit- ment a training of an outreach staff component; A) Successful entree into the target community; 5) Development & distribution of health promotion materials, condoms and small bottles of bleach; 6) Use of indigenous field assistants, who are natural leaders, to help promote safe health practices; 7) Utilization and management of the media to promote the project's goals; 8) Evaluation and reassessment of project plan and ensuring compliance with health messages, a 9) Entry into new IVDU scenes, when and how to move beyond the original target groups. An administrative project evaluation indicates that, contrary to popular wisdom, IVDUs will change their behavior, especially in relation to sani— tizing their shooting paraphernalia. WP198 Patients with Kaposi's sarcoma who opt for alternative therapy: inmune and psychological measures. ELINOR M.LEvv:, M.COTTRELL***L.H.KUSHI***,and P.H.BLACK*,*Boston University c 00 o edicine,Boston,MA,* Fashion Institute of Technology,NV,***University of Minnesota,Minneapolis,MN. Twenty four men who have chosen a holistic approach to their diagnosis of Kaposi's sarcoma have been studied sequentially. They are all following a macrobiotic regimen. The median survival for the 8 men who have died is 19 months (range 5-46 months). None of the surviving members of the cohort have required hospitalization. One has required local radiation. Four are alive 3 or more years after diagnosis. Contrary to what might be expected, the number of lymphocytes in the group has increased with time over the first 3 years after diagnosis (r=0.474,p=0.006). The number of T4 cells increased over the first 2 years after diagnosis (r=0.458,p 0.03). The percentage of T8 cells was unchanged (=— 0.06,p=0.69). A subset of approximately 1/3 of these patients have filled out psychological questionnaires,including the Beck Depression Inventory (BDI) and the McNair's Profile of Moods Survey (POMS). Preliminary data suggests these men are generally less depressed (median BDI score 10, range 1-28),less anxious (median POMS Tension score 4,range 3-6),and feel more energetic (median POMS Vigor score 23,range 8-32) than has been reported for other cohorts of men with AIDS. The psychological profile associated with this group is hypothesized to have a beneficial effect on the clinical course of their disease. 143 WR199 Patterns of Distress Following HIV Antibody Test Notification. ROBERT STEMPEL*, J. MOULTON**, T. KELLY*, D. OSMOND*, A.R. MOSS*, *University of California, San Francisco, **Langley—Forter Neuropsychiatric Institute, San Francisco, CA., USA. The psychological impact of informing at-risk individuals of their HIV antibody test results is assessed in a group of 108 gay men from San Francisco, 66 of whom elected to be notified of their results. Of those notified, 44 were seropositive and 25 were seronegative. We compare self- report measures of psychological distress and potential psychosocial media- tors prior to receipt of results, and again two weeks and three months following their notification session. We found a small, but significant, (p<0.03) increase on the Beck Hopeless— ness Scale, but no significant increase in several other measures of distress following notification of seropositives. We found a significantly higher perceived risk of developing AIDS at baseline (P‘0.01), among both seroposi- tives electing to know their results than among subjects who elected not to know. This difference persisted at three months post—notification even among those notified of a negative serostatus. This lack of substantially increased distress following notification of seropositives may be explained by the subjects participation in a prospective epidemiological study which has returned clinical and immunological information to participants, and by participants' expectation of their serostatus (96% of seropositives correctly anticipated their serostatus). Our group may resemble many at—risk populations in having long considered themselves to be seropositive, and so at decreased risk of severe adverse psychological reactions to antibody test results. wnzoo The Unique Counselling Interventions Required for Intravenous Drug Abusers (IVDAs) with AIDS/AK: and their Families Catherine Lyons, M. Cossabocxn, V. Graham, E. Honey, 5. Iandesman, Kings County Hospital Center, AIDS Team, Brooklyn, NY. The psychosocial and econunic realities surrounding people infected with HIV who are IVDAs, or sexual partners of IVDAs warrant particular counselling interventions. The population is predmdnantiy poor, black, and hispanic for whom the diagnosis of AIDS ourpounds pre—existing social. and eoonanic stressors, as well as the effects of long term chronic drug abuse. SYstems must be set up to provide an interdisciplinary approach in a coor- dinated and integrated manner Eran diagnosis to death. Entire families become the clients - be they parents and babies who are all sick with AIDS/ARC or in— fected with HIV or be they adult siblings who used IV drugs together and are now being cared for by other family members. Counselling interventions are directed at the emotional and social impact of an AIDS/Am diagnosis in conjunction with the unique pre-existing psychosocial variables in this population. Sane of these include: l)l:hat day—to—day survival issues are frequently the primary psychosocial concern, thhe sense of alienation and expend/ability already experienced that is oonpoxmded by the diagnosis, 3)the feelings of low self esteem absorbed from society's view of the associated high risk behaviors this diagnosis may reinforce, 4)that drug abusers may have severed relations with family and become particularly isolated. For health care providers to provide conpassionate care, as well as in order to disseminate proper information regarding transmission of HIV to IVDAs and their sexual partners, systems mist be established that address the particular needs of this population. A Longitudinal Study of Distress and Coping In Men with AIDS and AIDS Related Complex W, D.M. Sweet, J.M. Moulton, J. Zich University of California School of Medicine San Francisco The problems associated with AIDS spectrum disorders transcend the medical dimension of the disease. In a 5-year study, we are documenting the psychosocial impact of events that occur along the disease continuum. Fifty gay or bisexual men with AIDS, recruited from San Francisco General Hospital, were administered a battery of standard self-report measures of distress and coping 2-8 weeks after diagnosis, and then 4, 7, and 15 months later. Fifty-three men wit ARC were administered the same battery at the same intervals except the 4-month follow-up. Surprisingly, the number of self-reported AIDS-related "hard" or "soft" symptoms were only correlated with two measures of distress at the initial assessment for men with AIDS, and were not associated with distress at any follow-up point. At the initial assessment point, men with ARC reported-—unexpectedly-—higher_ levels of anxiety, confusion, depression-dejection, fatigue-inertia, tension, and anger- hostility than men with AIDS. Seven months later, however, these group differerencos had diminished. Men with AIDS were significantly more confused at the initial assessment than at 4-month follow-up, and were significantly less anxious 7 months later. Men with ARC were significantly more anxious 7 months later than initially, but also significantly less hopeless. The psychological coping style of 'Hardiness" was significantly negatively correlated with all scales of distress and mood at initial assessent for men with ARC. In a multiple regresison analysis, loss Hardiness was the best predictor of overall distas. Hardiness played less of a role, however, in effecting distress for men with AIDS, or for men with ARC at follow-up assessments. Data for the 15-month follow-up will be presented, as well as implications for psychosocial interventions. WE201 WEDNESDAY, JUNE 3 wnzflz The Importance of Supportive Interventions for Caregiving Family/ Friends during the AIDS Crisis. SANDRA JACOBY KLEIN*, w. FLETCHER.* * *private practice, Encino,CA;AIDS Project Los Angeles;UCLA Division of Cancer Control,Los Angeles, CA. **AIDS Project Los Angeles, Veterans Administration Medical Center West Los Angeles, CA, USA. Long term institutional care for AIDS or ARC patients is often unavailable in many communities. After periods of hospitalization the burden of continu- ing care may fall upon the patient's family and/or friends. These caregivers have become an important resource in the overburdened AIDS treatment network Consequently it is vital that they be given the support and training necessary to enable them to persevere despite overwhelming obstacles. As Co-therapists of ongoing grief recovery groups over the past three years, we have observed surviving family members and friends as they related diffi- culties encountered relative to their unmet needs during the period preceding the patients‘s death. Many in this already high—risk population found them- selves without adequate social, legal, financial or emotional supports; knowledge of available community assistance programs; or nursing skills to care for the patient at home. They were neither able to communicate with health care professionals nor understand and cope with changes in their re- lationships. They tended to experience more depression, fatigue, guilt, anger, helplessness and illness both before and during the mourning period than did survivors who felt that their needs were met. We offer a program of education and supportive interventions that could free these caregivers to continue a level of essential care by reducing immobiliz- ing stresses. This ancillary support network for health professionals and persons with AIDS/ARC will then be maintained. wnzua Pruin'ding Psychological Support to Children with ABE LEWIS KA'IOFF, Ph.D., Gay M's Health (risis, 1w York City, {EA here have been apprmdmately 400 children with Am reported to U.S. Gaiters for Disease Oxnxol, and estfimues of over 3,000 unreported or mrfiagnosed cases. A large penaanzge of these childrexy 802 ofwl'nnare theoffspring of IVdrugabusers, are inflieNewYorkiretmpolitan area. Linited social and emxathmrfl services, as well as a lack of amnxscy for children with AJIS is cannxn In Daxmher of 1985, the Gay Men's Health Crisis began a volunteer program serving children with AIIS and their families. All direct servhxs are pnmdded by volunfl¥zs, in hospital or at hue. lhe'ilfldies" pnmdde social and developnaual sthmflatMXIfor childrem vmile'lkisis Interventionlkxkers” are focused on emnional support for parents and unegbnxs, child advocacy,refarals to social services and extitlemt programs. So far, we have worked with 25 children, between 12 months and seven years of age. Problem of these childrm and families, as well as services pnmdded will be naxmted VVEZO4 Fostering and adoption of infants at risk of HIV infection 5 Skinner, J Mok, RP Brettle, Lothian Region Social Work Department and City Hospital, Edinburgh, Scotland. To date we have cared for 25 babies at risk of acquiring HIV from 24 mothers. Three mothers acquired the HIV infection by heterosexual contact the rest via intravenous drug misuse although only 9/21 are currently abusing. Eight out of 24 were single parent families and there were immediate demands for adoption or foster care. Thirty four foster families offering places to babies were approached and following interviews 3 offered to care immediately for a high risk baby. Twenty seminars followed, initially conducted by a social worker and physician and latterly by a social worker resulted in 12 further families being identified for these infants. To augment all family placements, a pool of 20 specially prepared nursery nurses are available to cover family illness. Short term emergency care was provided by an Infectious Disease Unit but to date no at risk, or high risk child has required long term hospital or residential care in Edinburgh. The likelihood of children returning home diminishes with the length of time in care and plans are being made for the future of the fostered children. The local authority's commitment to giving children as normal a life as possible in securing foster and adoptive families has been aided by well prepared, flexible families who care for children with a range of special needs. general method is now being adopted by other local authorities faced with similar potential problems. The 144 WR205 surge Rpcruitment and Screening of Patients for AIDS Research ro oco s MARGARET MEGILL, B. HERPIN, B. BAIRD, National Institutes of Health. Bethesda, s t e number of AIDS cases and the number of investigational drug studies have increased, an efficient yet individualized screening process for matching patients to particular protocols is required. In order to focus and expedite patient recruitment efforts, protocol-specific checklists were formatted by the nurses and used in their telephone conmunlcation concerning 760 referrals. Among the elements found to be most valuable were relevant patient history (Kaposi' s sarcoma, type of opportunistic infections, current symptoms), hemoglobin, and T4 numbers. A cut-off of 200- 400 T4 cells was found to be helpful in distinguishing patients with a high risk of developing an opportunistic infection during study. Following initial telephone selection, 277 patients were scheduled for a screening visit to NIH, limited to HIV culture of blood, an innmne profile, CBC/diff, SMAC chest x-ray, and a brief nursing interview. Obtaining a chest x-ray at this early point in screening helped identify patients with unsuspected abnormalities who were not appropriate candidates for research but who required routine medical follow-up. Utilizing personal computers and the NIH DEC-10 system, a computerized data retrieval network was established into which results from either the clinical pathology laboratory or the various research laboratories were entered as generated. Once data collection was complete, the patient was reviewed by the research nurses and the senior investigator, a decision made as to protocol eligibility, and the patient and the referring physician notified. Only then were history and physical scheduled for suitable research candidates, of whom approximately 83 of 107 were found to be protocol eligible. Thus, preliminary phone and blood screening evaluation may greatly enhance the efficiency of screening patients for research protocols. wazofi Dilemmas of an AIDS Residence Program: the Legal, Ethical and Psychosocial Issues Integral to a Program and its Residents ELLEN COUSINEAU, RN, MHS, Director, Shanti Residence Program, 890 Hayes, San Francisco, CA New existing in many parts of the United States and Europe, housing pro— grams for people with AIDS are a vital community resource. By coupling stable, low—cost housing with advocacy services, AIDS residence programs enable PWAs to remain as independent as possible, in a supportive home—environment. Such programs do not always run smoothly. In spite of -— or perhaps because of -— proceeding "with the best of intentions," AIDS residence programs are forced to continually re-evaluate the ways they operate. What flexibility is needed in interpretting program policies? How does a program carefully screen applicants without discriminating against the dis— ease itself? What must a program know about tenant rights and probate? How sick is "too sick" to live independently? How does a program avoid inter- agency combat-zones? This paper provides case studies demonstrating ways in which Shanti Resi- dence Program has, since 1983, dealt with these and other issues. It hopes to increase sensitivity and problem-solving capabilities of persons who inter- act with —— or hope to form -- AIDS residence programs. View From Within - Coping With Isolated Thrombocytopenic Purpura WBZW In e B. Corless* D. Abrams**, E. Biglieri**, M. Dodd** *University of North Carolina, Chapel Hill **University of California, San Francisco The significance of how individuals perceive themselves and their illness and the effect on recovery has too often been given inadequate attention. This paper reports the results of the interview data and the drawings of eight homosexual males with Isolated Thrombocytompenic Purpura who participated in research on the impact of a psychophysiological intervention on psychological. physiological and inmunological parameters. At the study's onset an interview was conducted in which questions of the meaning of the illness, its timing, previous approaches to coping with crisis, life changes which they desired to make, and factors considered important for maintaining their present level of functioning were asked. In subsequent interviews discussion focussed on coping, and changing perceptions of life and its meaning. Interview responses were compared with adults with acute leukemia undergoing induction chemotherapy. The latter although mentioning their own resources emphasized the help to be provided by doctors, nurses and chemotherapy. The men with Isolated Thrombocytopenic Purpura noted their own inner resources. This was substantiated by the cancer Locus of Control Scale. The homosexual males as compared with three other groups were higher on Internal scores and lower on those for Chance and particularly, Powerful Others. Changes in self perception over time were indicated in drawings in which participants depicted themselves, their illness, mood changes and approach to life. WEDNE DAY, JUNE 3 wpzua Evaluation of an Educational Program to Help Perinatal Nursing ' Staff Provide Care to HIV Infected Patients KATHERINE M. NELSON, R. FAHRNER, J.B. COHEN, Dept. of Staff Development and Research, San Francisco General Hospital, San Francisco, CA, USA. The increased incidence of perinatal HIV infection has had significant impact on nursing care practices in Labor and Delivery and the Nursery. Nursing staff education and support are necessary to circumvent exaggerated fears of AIDS. At SFGH an educational and support program has been developed to facilitate high-level nursing care standards as well as appropriate multidisciplinary patient management. Program methods were: I) a baseline survey of knowledge and attitudes about AIDS prior to the intervention program; 2) a multistage intervention program extending over a A month period, and 3) a post-intervention evaluation exam— ining knowledge, attitude, and behavior changes. Intervention programs were for all nursing staff in Nursery and Labor and Delivery (NaAS). Strategies in— cluded open staff meetings, didactic programs, onsite reinforcement, and implementation of perinatal HIV infection control gdidelines. Results: Changes observed included increased knowledge about HIV transmission and infection control. Staff also demonstrated increased sensitivity to more appropriate discharge teaching and made increased numbers of referrals for follow-Up. Some nurses increased their skills in providing patient education about prevention of HIV transmission. Attitude changes were less predictable and more complex. Changes tended to proceed through several stages, but most staff reported reduced fear and more confidence in caring for HIV infected patients. wnzog Nursing Staff Knowledge, Attitudes and Self—Reported Behavior with Respect to Patients with AIDS. MARY ALICE O'DOWD, N ADACHI, AM RAZIN, RS KLEIN. North Central Bronx Hospital, Montefiore Medical Center, Albert Einstein College of Medicine, Bronx, NY, USA. AIDS has evoked considerable fear and anxiety in the general public and among health care workers. A study of the attitudes, knowledge, and self-reported be— havior with respect to AIDS of a group of 135 nurses and student nurses, 126 of whom worked in a large municipal hospital in NY City with an average daily cen- sus of lb patients with AIDS or ARC, was done. A questionnaire was administered between 9/12/85 and 11/5/85. Confidentiality was ensured. Demographic data were obtained and subjects were asked to rate on a 5 point Likert scale 115 statements. All statements were ordered randomly and both positive and negative phrasing were used. Sixty-six statements dealt with knowledge, attitude and self—reported behavior in relation to AIDS and AIDS patients. For comparison, 16 of the statements were repeated with respect to three other diseases, which shared with AIDS the possibility of transmissibility (tuberculosis), of patient behavior in causality (emphysema), or both (hepatitis). This initial survey found that while these nurses shared the fear and anxiety of the general public about AIDS, (57% worried about hospital transmission of HIV and 44% worried about the risk to themselves of opportunistic infection), they were able to make distinctions as to the risks to themselves and other patients, based on current knowledge about the four diseases surveyed, for 12 out of 16 disease comparison questions (p(.05). Although AIDS patients were blamed for their illness by 7-372 of the nurses, most nurses (72-87%) demon— strated a consistent attitude of compassion. Risk group was not a factor. This study instrument appears to be a valid means of assessing staff knowledge and attitudes towards patients with AIDS. Cost of Medical Care for AIDS Trends over a two year period QEQBQE-B;§EAGE.LIL*-5- LANDERS*.k in Massachusetts WP.210 EARRY*.G. LAHBA.L BPSTEIN“. KBoston Department of Health and Hospitals M‘Instltute for Health Research. Harvard School of Public Health. Boston. Ma Our previous work indicates that the inpatient cost of medical care for a group of "5 AIDS patients treated at one Boston hospital 15 $02,517 per patient per year. To evaluate the consistency of cost over time and by institution. a two year study of all 215 AIDS patients treated at 5 Massachusetts hospitals was conducted. These patients represent 75% of all AIDS patients treated in the state during 198” and 1985 Preliminary results indicate that the yearly inpatient cost per patient at each site varied from $u2.517 to $63.u77. and the cost was inversely related to the total number of AIDS patients treated at the Site during the study period. Over the two year period. each study site showed a decrease in cost and the mean cost per case decreased from $50,087 to 336.996 (p<.01). The observed decrease was related both to shorter lengths of stay (mean 15.7 days/hosp. down from 19.2 days/hosp,) and a decrease in the mean number of hospitalizations (2 2/pat1ent to 1.9/patientL The results of treating persons data will become the country with this study indicate the inpatient cost of with AIDS is declining. Clarification of this important as the epidemic spreads into areas of few AIDS cases to date 145 Service Characteristics of U.S. Public and Teaching Hospitals with AIDS Patients WP.211 D.P. ANDRULIS, Ph.D.*, VIRGINIA S. BEERS, M.P.A.*, J. BENTLEY, Ph.D**,L . GAGE*, *National Association of Public Hospitals, Washington, DC, USA,**Council of Teaching Hospitals, Washington. DC, USA. A 1985 AIDS survey of 450 major U.S. public and teaching hospitals conducted by the National Association of Public Hospitals and the Council of Teaching Hos— pitals has yielded responses from 223/450 institutions. These hospitals, which treated almost 5,000 patients in the calendar year, were asked to identify the presence or absence of the following services to AIDS patients: separate AIDS unit; specifically designed system to monitor or track patients on an out— patient basis; a formal suicide watch program, training protocols for AIDS staff in hospitals ; education programs for non AIDS staff; formal linkages with various community groups representing high risk populations (homo— sexuals, minorities, drug users, hemophiliacs, women at risk). Responses were analyzed according to four major institutional characteristics: hospital size, location, ownership and number of AIDS patients served. Findings describe similarities and differences among the institutions with regard to tendency for hospitals to establish AIDS units, the extent and type of hospitals able to coordinate and integrate inpatient and outpatient care, the emphasis on formal suicide prevention approaches, the extensiveness and sophistication of AIDS training programs, and the extent to which hospitals coordinate AIDS treat— ment with the key community groups. WP212 Canprehensive Case Management Utilizing Hospice Concepts: A Statewide Program IXNNE CRAWFORD, New Mexico AIDS Services, Inc., Albuquerque, New Mexico, USA New Mexico AIDS Services is the only AIDS service organization in New Nbxico and offers case nanagenent services for all persons with AIDS/AR: in this rural state. Case nanagenent is based on the Hospice concepts of: a wholistic View of client needs, an interdisciplinary team approach to fleet those needs and the pnanstion of quality of life. We utilize trained volunteers and existing ctnr nunity resources to reduce hospital in—patient days and therefore the cost of patient care by increasing in—hcne and out—patient support. The case nanager's role includes acting as: a client advocate; an educator- resource person to Radical professionals; and a coordinator of support services. Another important element of a case nanagement program is counseling of FWAs in regard to: living wills, power of attorney, medical guardianship, right to refuse treatnent, inforned consent and confidentiality. The developnent and delivery of a comprehensive case nanagamt program in- volves establishing liaisons with existing services that provide in-patient acute and long term care; hcnecare and hospice nursing; delivery of meals and hcnrnaker services; transportation, social service counseling for disability incane and financial support. These liaisons optimize out-patient support and pnanate the education of ccnnmnity resource persons. To assure services to clients who live in rural areas the case nanager must identify and educate health care professionals and arrmopriate resources in those areas by offering inservices, guidance and support. The case management services are offered in adjunct with an enotional support and counseling program and are available on a 24 hour a day basis. wP213 Enhancing the Coping Skills of Families of Children with AIDS ' MARY TASKER, P. EVANS, M. BOLAND, J. KERESZTES, E. CONNOR, J. OLESKE Children's Hospital of New Jersey & UMD—New Jersey Medical School, Newark, NJ The AIDS program at Children's Hospital of NJ is a multidisciplinary, multi- service program that utilizes a chronic illness model in providing care to children andsupport services to their families. In 46/50 families with a child with perinatally acquired infection, diagnosis in the child resulted in identification of a primary caretaker (30/50) and sibling (7/50) with HIV infection. Initial response to the diagnosis included prolonged (longer than 3 months) denial in 12/50. In 6/12 denial interfered with acceptance of services for the child. Development of symptoms in the parent was associated with improved utilization of services for the child. Primary caretakers identified a need for asisstance in the following areas: access to entitlements (welfare, medicaid, NIC) 31/50, transportation 27/50, housing l6/50, school entry 9/50, decision making related to medical care 30/50, assistance with family problems unrelated to AIDS 30/50, medical care and service for the parent 12/50. When provided w1th the opportunity for ongoing therapy. 1/10 parents followed through on the referral. The social worker‘s role is to assist the caretakers to define their own needs realizing that the perceived need may be for concrete services rather than counseling and psychological support. Social work Interventions are directed towards linking families with services and helping families adapt to chronic illness. WEDNESDAY, JUNE 3 WBZ14 A Hospice's Response to the AIDS Dilerrma ROSEMARY J. HURZELER, R.N., M.P.H., H.A., DIANNE RAWSON, R.N., M.S. The Connecticut Hospice, Inc., Branford, CT. The Connecticut Hospice, Inc., the first hospice in America and the only teaching hospice to offer ACCME credits through its Institute training pro- grams, examined in Dec., 1983 the question of whether the current criteria for admission to Hospice inpatient and home care settings allowed for the admis- sion of patients with AIDS. On April 11, 1984 the Medical Board voted that such criteria did fit. Between April, 1984 and July, 1985 a series of steps were undertaken to implement this decision including: multiple inservices for paid and volunteer staff and families on infection control aspects and psycho- social issues involving the State, user-friendly hospitals, Shanti Project in San Francisco; the administration of Hepatitus B vaccine to all patient care- givers. The first person with a diagnosis of AIDS was accepted in July, l985. Since then Hospice, inpatient and home care, has seen many patients (12 case reviews) with a diagnosis of AIDS with various causes of onset and has worked extensively on psychosocial issues with those patients, families and signifi— cant others. As this Hospice is a statewide facility and these patients have come from all over the State, there has not been a time when it has not ac- cepted a referral (AIDS). In recognition that there has been several patients who have been inappropriately institutionalized in acute care settings who are neither eligible for hospice inpatient and do not have a home, this led Hospice to undertake a hospice home for the homeless. WRZ15 Prospecpive HIV Serologic Survey of Employees in a Canadian Teaching Hospita NORBERT GILMORE, S-L TAN, J C MCDONALD, S JOTHY, N CHERRY, M O'SHAUGHNESSV, P GILL. Division of Clinical Immunology and Department of Pathology, Royal Victoria Hospital; School of Occupational Health, McGill University, Montreal; and Laboratory Centre for Disease Control, Ottawa, Canada. 1,496 employees at a 780 bed teaching hospital in Montreal have been enrolled in a prospective survey for evidence of HIV infection beginning June 1985. Work-related exposure to HIV and hepatitis B are being assessed by 6 monthly questionnaires and blood tests. During this study, 56 cases of AIDS have been diagnosed, resulting in 106 hospitalizations. The cohort includes 344 men, employed 3.5 years i 3.8 (SD), and 893 women, employed 2.6 years i 2.3, and 259 new employees (53 men and 206 women), working less than one month. The cohort consists of 275 administrative personnel without patient contact (18.4% of the entire cohort); 322 support and maintenance personnel with variable patient contact (21.5%); 93 physicians (6.2%); 614 nurses (41.0%); and 192 laboratory technicians (12.8%). Sera were assayed for HIV antibodies by ELISA assay; the nspecificity of repeatedly reactive sera was verified by Western blotting and an immunoblot assay, using cloned gp160. Sera from 10 employees were repeatedly reactive on HIV-ELISA testing: 4 subjects were initially reactive (2 male and 2 female) and 6 were initially negative but found to be reactive 6 months later (4 female and 2 male). Only one male with a history of sexual exposure to HIV was seropositive by Western blotting and gp160 inmunoblotting. This study has failed to identify occupational risk for HIV infection, associated with hospital work, and confirms the very low prevalence of HIV seropositivity in urban non-risk populations in Canada. VVP216 Evaluation of the antiviral activity and tolerance of ' HPA23 in 38 patients with HIV related disorders. DANIEL VITTECOQ*.B.AUTRAN*,B.ROUQUETTE**,JC.CHERMANN**,R.WOERLE***. St Louis Hospita1,**Institut Pasteur,Paris,***Rhone Poulenc,Lyon, France. 22 AIDS (12 KS,7 01,3 KS/OI) and 16 preAIDS patients staged accor ding to the Walter Reed classification (3 WR5,4 wR4,l WR3,8 WRZ) entered a HPA23 protocol: 2 IV injections per day (3mg/kg/day) during 14 days.48 treatments were provided.7 patients had a thrombo penia<150 000 before treatment.After treatment 15 patients had a reversible thrombopenia<100 000 ( 5<50 000 ). Reverse transcriptase activity was studied by culture and cocultu re of the blood and CSF before treatment.Viremia was studied in 17 cases after HPA.Coculture was taken into account only when culture was negative.0n blood cultures,viral inhibition was defined as a decrease of at least 400 000 cpm or a delay 10 days of the reverse transcriptase peak, failure as an increase of the activity and stability as no significant modification.Considering viral activity in the blood,among 6 patients with positive CSF culture before treatment,we noticed 2failures,2 inhibitions,2 stabilities.Among the others,we noticed 2 failures, 7 inhibitions and 2 stabilities. This study confirms that a short HPA23 treatment appears to inhibit viral replication in blood,and side effects are not limiting factors.We suggest to carry on this study with higher dosages and shorter courses which could be repeated every 2 months. 146 WP217 Mycobacterlum Avium Complex Isolated from the Lung Only, Does it ' Disseminate? TIMOTHY P. MESS. San Francisco General Hospital, San Francisco, U.S.A. In December 1986 a retrospective review was conducted to investigate for dissemination of Mycobaccerium avium complex (MAC) in AIDS patients who had culture proven MAC from the lung only. From January 1982 to October 1986, 107 patients had MAC cultured from the lung at SF General Hospital (SFGH). 22 of these patients had negative blood cultures for AFB at the time of their posi- tive lung isolate. 16 of these 22 had follow-up AFB blood cultures of )1 month to investigate for dissemination and in 5/16 (31.3%), these cultures were positive for MAC. The last negative blood culture was at 21-224 days (median 100 days). The first positive blood culture was at 24—280 days (median 171 days). All 5 patients had significant diarrhea preceeding their MAC blood isolate. 2 had cryptoeporldium, 1 had CMV colitis and the other 2 had uptake of gallium in their colon. (Stool AFB's are not available at SFGH.) Only 1 pa— tient had an abnormal CXR suggestive of pulmonary MAC disease (hilar adeno— pathy). 2 of these 5 patients received anti—tuberculosis (anti-TB) medications for 2 and 5 weeks prior to their dissemination. The 11 patients without evi- dence of dissemination had follow-up with negative AFB blood cultures of 31- 442 days (median 112 days). 6 of these 11 patients received anti-TB meds (range; 2—8 months, median; 6 months). Only 2/11 complained of diarrhea and none had known intestinal pathogens. Only 1 patient had an abnormal CXR suggestive of pulmnary MAC disease (cavitary lesions) which improved with anti-TB meds. In these 11 patients 7 had 10 repeat sputums for AFB. 2 of 3 patients treated with anti—TB meds had a positive repeat sputum culture for MAC. Overall, 6/10 repeat sputum samples were negative for any AFB. Dissemination of MAC is associated with diarrhea. Use of anti—TB made is of uncertain value. Use of EPA-23 in Patients with AIDS: WP218 an Eight Week Trial. GEORGE F. MCKINLEY, A. ENGLARD, K. WGI M. LANGE; E.B. KLEIN, M.H. GRII‘XX): St. Luke's7fievelt Hospital, Columbia University. New York, NJ. 10019. As part of a mu1ti-center phase I trial, the experimental antiviral agent EPA—23 (Heteropolyanion—ZS, or antimonio-tungstate) was given to 16 patients with CDC—AIDS (10 with Pne stis carinii pneumonia, 4 with cutaneous or oral Kaposi's sarcoma, one with both m Ks, and one with Candida esophagitis). Protocol required five daily intravenous injections per week, and lasted eight weeks. Four dosing levels were used (0.25, 0.5, 1, or 2 mg/ kg/day) with four patients assigned to each level. Four patients did not complete protocol because of intercurrent illness (one had rapidly progressive KS and three required conventional antibiotic therapy). The only immediate toxic reaction occurred upon extravasation of drug, on at least one occasion in each subject, and was characterized by rapid onset of pain followed by erythema and swelling around the injection site. Symptoms persisted for 3 to 5 days after extravascular injection, but there were no long term sequelae. Subjective side effects included a slight metallic taste noted by several patients and nausea and loss of appetite. The most consistent toxic effect was a decrease in platelet count which occurred in all twelve patients who completed protocol. Platelet counts (x1000): week 1: 193 + 14 SEM, week 5: 124 1 13 week 9: 97 1 16. Marked leukopenia ( < 2000) occurred in a few patients, but did not persist on continuation of HPA—23. Renal function remained unimpaired. Moderate elevation of transaminases did occur in the group receiving the highest dose. Overall, HPA was well tolerated in this group of 16 patients with AIDS. Observed Toxicity During wp_219 Topical Acyclovir for Treatment of Hail—y Ieukoplakia MAKIUS A. CONAN'I‘, B. NBNLIN, M. ILLEMAN, Center, San Francisco, CA. This is a double—blind placebo—controlled crossover study to test effective- ness of 5% Acyclovir ointment in controlling lesions or oral "hairy" leuko- plakia (HL) in a group of ixmunosuppressed volunteers infected with HIV. I-IL was described by Greenspan, Greenspan, and Conant in 1985, and is charac— terized as a white, adherent, often fillifom oral lesion found mainly on lateral tongue borders with characteristic histologic appearance showing fine keratin projections, koilocytosis of prickle cells, and little subepithelia inflammatory cell infiltration. There is evidence of Epstein—Barr virus in the epithelial cells. EL has been observed only in ixmmnosuppressed individuals, a great many of whan are homosexual males, sempositive for HIV antibody. It is highly asmiatcd with progression to AIDS in these individ— uals. Treaunent of lesions of 1.1. is useful in relieving patient anxiety and removing lesions which might be confused with oral candidiasis. Twenty subjects with clinically diagnosed HI. applied ointment to lesions 5 times a day for 4 weeks (2 weeks ACV ointment, 2 weeks polyethylene glycol base placebo). Nystatin suppositories were dissolved orally twice daily during the month of treatment and candida cultures were done both before and at the caipletion of the study to eliminate confusion of BL with oral candida. Clinical evaluations, including photographs of the lesions, were done weekly. A beneficial effect of study medication ointment has been deserved in same patients, suggesting that topical ACV may be effective in suppressing Epstein-Barr viral replication in these lesions. University of California Medical WEDNESDAY, JUNE 3 WRZZO Treatment of Pulmonary Kaposi's Sarcoma with a Combination of Adriamycin, Vincristine, and Bleomycin. m L Mgngkg. 5t. Luke's/Roosevelt Hospital Center, New York, New York. Pulmonary Kaposi's sarcoma (K8) in AIDS is a late manifestation usually diagnosed in patients with extensive cutaneous disease. In one series the median survival after diagnosis was 1.5 months. Between 7/85 and 1/87, 12 patients with extensive pulmonary K8 were seen. Patients ranged in age from 23 to 61 years (mean, 38 years). 2 had received prior chemotherapy. There were 5 patients with B-symptoms and 2 patients with a prior opportunistic infection. All patients had extensive cutaneous and endobronchial involvement with rs, pulmonary symptoms, and negative gallium scans. Other problems included hemoptysis in A and serosanguineous pleural effusions in 2. The chemotherapy regimen consisted of Adriamycin 50 mg IV on day l, Vincristine 2 mg IV on days 1, 8, and 15, and Bleomycin 150 IV days 1 and 15 of a 28 day cycle. All patients received dapsone 25 mg po qid as prophylaxis for PCP. 6 patients initially received a reduced dose of Adriamycin because of leukopenia. None had a measureable response and the mean survival was 1.5 months. In contrast, all 6 patients who received the full dosage achieved greater than 752 clearing of their pulmonary infiltrates, resolution of their pulmonary symptoms. and had a mean survival of 10 months (range 7 to 12). A of these patients required a reduction in the dose of Adriamyc‘in after 3 to 7 cycles because of leukopenia. Progressive pulmonary KS appeared within 3 months in these patients. To date, 10 patients have died, 9 of pulmonary KS and l of sepsis. No patients developed an opportunistic infection. Toxicity included mild myelosuppression, moderate alopecia, and mild nausea and vomiting in all patients. Our results indicate that this regimen is effective and well tolerated in the subset of patients who have adequate bone marrow reserve. Major Opportunistic Infections in AIDS Patients after More than Eight weeks of Azidothymidine (AZ'I‘) Therapy. m M. 51.14. LEW, and EN. Heseltine. L08 Angeles County/Univer- sity of Southern California Medical Center. Los Angeles, CA USA This report examines the frequency, types, and outcomes of AIDS-defining opportunistic infections (OI's) in patients treated with AZT for more than 8 wears. 'merzty-two patients with previous Wis mm“, pnemonia (PCP) were enrolled in our study. Nineteen of the 22 conpleted more than 8 weeks of MT therapy. Eleven patients were treated with 250 mg every 4 hours for 10-12 weeks and then 200 mg every 4 hours thereafter. The other 8 patients were treated with 200 mg every 4 hours. AZT was discontinued or reduced to 100 mg every 4 hours if patients developed granulocyte counts of (750 or platelet counts <50,000. Eight of 19 patients (42%) developed remrrencs of PCP. These infections were documented between weeks 10-24 after starting AZT. Most of these recurrences were mild as treasured by febrile days, arterial oxygen tension, and length of hospital stay; two of five tested had negative lung gallium scans. However, fatal complications developed in 2 of the recurrent PCP patients, one from respiratory failure due to PCP and another due to severe candida esophagitis, aspiration pneumonia, and lung abscess. Two patients developed cryptococcal meningitis at weeks 12 and 20; one died. me patient, at week 24, developed peri-rectal herpes sinplex ulcerations which persisted > 1 month despite concurrent acyclovir therapy. In summary, 12 out of 19 patients (63%) developed major OI's after week 8 of AZT therapy. Three of these OI's were fatal. While AzT therapy may decrease the incidence of OI's initially, such Cd's continue to occur and can result in fatalityu WP.221 WP222 Blood Levels of Pentamidine in AIDS Patients (Pts) Receiving Monthly Prophylaxis SJ REHM*, c KARAFFA-MYLES*, JE CONTE, JR**, *Cleveland clinic Foundation, Cleve and, 0H. **UCSF, San Francisco, CA. Pneumocystls carlnii pneumonitis (PCP) recurs in 20 to 70% of AIDS pts; most are unable to tolerate prolonged oral TMP/SMX prophylaxis. Pentamidine prophy- laxis 15 appealing because of its prolonged tissue half-life, but the pharmaco- kinetics in pts receiving intermittent doses is not known. Preliminarystudies indicate a decrease in PCP recurrences with monthly pentamidlne prophylaxis. Eight pts receiving monthly intravenous infusions of pentamidlne at a dose of 4 mg/kg were studied. All had received previous pentamidlne therapy for PCP (avg. total 3338 mg), and all had at least one dose of prophylactic pen- tamldine (avg. 5.6 doses) before blood levels were determined. The average cumulative prophylactic dose was 1526 mg. An HPLC assay with a sensitivity limit of 2.29 ng/ml was used to determine peak and trough pentamidine blood levels. Levels were performed 2 or 3 times for each pt. In 6 of 8 pts trough blood levels were consistently detected; one pt never had detectable trough levels and another had intermittently detectable levels. Peak blood levels averaged 949 ng/ml (range 130-2612 ng/ml). The presence of detectable trough levels and the magnitude of the peaks did not correlate with the cumulative dose. Two of the 8 pts had recurrent PCP; one had discontinued pentamidlne prophylaxis when AZT treatment was initiated, and one other was terminally ill with disseminated MAI infection and Kaposi‘s sarcoma. Detectable blood levels of pentamidine are present for at least one month after a 4 mg/kg intravenous dose in AIDS pts who have received previous therapy with pentamidine. Further studies of the pharmacokinetlcs of inter- mittently administered pentamidine are in progress. 147 ROBERT YARCHOAN*, G. Improvement in HTLV-III/LAV-Associated Dementia and Neuropathy Associated with Administration of 3'-Azido-2',3'—Dideoxythymidlne BERG**, M. FISCHL***, M. DALAKAS****, C.E. MYERS*, S. **NIH CC, and ****NINCDS, Bethesda, MD, and ***U. of WP.223 BRODER", et al. , Miami, FL. Neurological manifestations of HTLV-III/LAV infection are increasingly being recognized as an important clinical problem and, as has been shown by Drs. Shaw, Gallo, and coworkers, the brain is a major site of replication of HTLV-III/LAV. Based on these findings, we have administered 3'-azido-2',3'—dideoxythymidine (AZT) to 7 patients with HTLV-III/LAV-associated neurological disease: A with dementia, 2 with peripheral neuropathy, 1 with both dementia and peripheral neuropathy, and 1 with a T10 paraplegia. Levels of AZT in the cerebral spinal fluid A hrs after a dose were 55% of simultaneous plasma levels. By 3 to 8 weeks after being started on AZT, each of the 6 patients with dementia and/or peripheral neuropathy had improvement in neurological dysfunction as assessed by examination, neuropsychometric testing, and/or nerve conduction studies. In particular, patients with dementia had substantial improvement in Trailmaking, Weschler memory, and pegboard tests. The patient with T10 paraplegia, however, did not improve. One patient whose dementia improved was studied by positron emission tomography (PET). At the start of therapy, he had a heterogeneous pattern of glucose metabolism with relative decreases in the posterior temporal, occipital and thalamic regions; a repeat PET scan after 13 weeks had become more normal. In 2 of the patients the improvement seen was transient, and they expired from pneumonia after 6 to 8 months of therapy; the other 4 patients who improved continue to do well after 2 to 16 months of therapy. These results suggest that certain HTLV—III/LAV—associated neurological abnormalities are reversible following the administration of anti-retroviral chemotherapy and they provide a rationale for a larger study in patients with this disorder. *NCI, w2224 Longterm Treatment of Severe AIDS and ARC Patients with Oral Ribsvirin: A Pilot Study CLYDE S. CRUMPACKER, G. BUBLEY, J. LOFTUS, S. HUSSEY, Beth Israel HospitaL Harvard Medical School, Boston, MA, U.S.A. A Phase I Study of oral Ribsvirin (RBV) for 8 weeks (Dec—June 1965-86) in 10 AIDS and 5 ARC patients showed suppression of HIV in blood, enhanced lymphoproliferative response to lectins and fewer opportunistic infections on RBV. On stopping drug, HIV was again detected in blood (Crumpacker et al., Proc. 2nd Int. Conf. on AIDS, Paris, 1986, p. 3A). To determine if prolonged use of RSV would enhance survival, 5 AIDS patients and 3 ARC patients who had survived the 8 week trial of oral RBV were enrolled in a study of continuous RBV at 600 mg/day in July 1986. AIDS patients had PCP as their initial opportunistic infection, had TA cells less than 100/mm3 (mean-SO/mm ) and none had KS at start of Ex. From July-Feb 1987, no patient has had recurrent PCP, and 6 of 8 are surviving. (In a comparable untreated group of 10 AIDS patients followed at BIH, 7 developed recurrent PCP in a mean time of 6.5 months.) Two AIDS patients died after A months on RBV with progressive AIDS encephalopathy, but no other infections were found. In 6 patients, 4 AIDS associated events occurred: 3 episodes of CMV retinitis (2 in 1 patient) 1 episode of candida esophagitis and 1 new KS lesion. In 3 ARC patients, one developed CMV retinitis to progress to AIDS. In the AIDS patients, initial clearing of HIV with RBV and enhanced lympho— proliferative response to lectina was associated with prolonged survival. Mean survival time from initial diagnosis of AIDS with PCP is 18.5 months (as of 2-1-87) in the 5 AIDS patients on prolonged RBV. REV is well tolerated as A patients have required no transfusions and 4 have required 2 units of packed REV/per month to maintain HGT-30. This pilot study of prolonged oral RBV in severe AIDS patients shows that RBV is well tolerated, associated with prolonged survival and fewer opportunistic infections. wpzzs Transplantation of Thymic Tissue to Reoonstitute the lnnune System of Patients with AIDS JOHN M. MER*, C.C. WCDD"*, G.J. NbNAMARA“, B. KINDER"*, *Departnent of Medicine, Prince Henry/Prince of Wales Hospitals, Randwick, N.S.w. Australia. **Division of Clinical Innunology, Yale University School of Medicine, New Haven, CT. U.S.A. Thynuc epithelial fragments were transplanted into 15 patients in an advanced stage of the acquired innune deficiency syndrone (AIDS). One patient was given interleukin 2 in addition to thyndc tissue. We demonstrated the following : (l) Thyndc epithelial fragments cultured before transplantation to renove T cells survived for nonths after transplantation in 8 of 15 patients and seened to be responsible for a partial, selective, but transient repopulation of the circulating T cell pool. (2) The absolute nunber of T8 cells, but not T4 cells, increased three to four weeks after the procedure in eight of the fifteen subjects. (3) This increase in T8 cells was associated with clinical inprove— nent and increased T cell responsiveness in vitro in scne cases. In one case a severe bilateral retinitis thought to be due to cytcnegalovirus (OWV) cleared spontaneously, a developnent unique in our experience with patients with AIDS. Inproved control of tuberculous infections was noted in two cases. The clearance of resistant pneggggyEtis carinii pneumonia and a cessation of previously intra- ctable diarrhoea in two patients coincided with engraftnent. (4) Ihynuc tissue transplantation as a single therapeutic nanoeuvre is unlikely to reconstitute the innune system of patients with AIDS, but the potential of the approach, used in conbination with agents that block replication of hunan T cell lympho- tropic virus type III deserves further study. WEDNESDAY, JUNE 3 wpzzs Evaluation of HIV Antibody Reactivity in Blood Donors with Atypical ‘ Western Blot Patterns NANCY L. DOCK*, H.V. LAMBERSON*, T.A. O'BRIEN**, $.R. PETTEHAY**, S. AIEXANDERF**, B.J. POIESZ****, *American Red Cross Blood Services, Syracuse, NV, USA, **E.I. duPont de Nemours & Co., Wilmington, DE, USA, ***Biotech Research Laboratories, Inc., Rockville, MD, USA, ****SUNY Health Science Center, Syracuse, NY, USA. Blood donors reactive for HIV antibody by ELISA who showed atypical patterns on Western blot (NB) representing several patterns of core protein reactivity (p15/p17, p15/p17 and p55, p24, p24 and p55, p15/p17 and p24) were followed for 2-10 months. Characterization of these antibodies was performed by I) use of recombinant HIV proteins and synthetic peptides, 2) determination of cross- reactivity to HTLV-l, HTLV-Il, HTLV-IV, 3) assessment of immune status and potentially interfering auto-antibodies. All but two donors maintained the same HIV core protein antibody reactivity throughout the follow—up period; one showed a diminished pattern; the other became fully antibody positive. Eighteen of 20 donor sera showed clear core reactivity with GAG-55 HIV recom- binant protein. Ten of 19 donors' samples demonstrated cross-reactivity to HTLV-IV; three of these 10, in addition, cross-reacted with HTLV-I. Immune status of all donors was normal, but rheumatoid factor was detected in 2 of 20. Thus our evidence so far strongly suggests that the atypical HE reactivity observed is directed against retroviral core proteins. As part of this study, donors were questioned during the follow-up visits. 0n interview, three donors reported possible risk factors for HIV infection that were not acknowledged at the time of donation. Based on these results, we conclude further study of donors with this "atypical" reactivity is warranted. As an interim measure blood identified by screening tests which detect antibodies reactive with core proteins should not be transfused. WP227 Low Dose Naltrexcne in the Treatment of AIDS ' Bernard Bihari, F. Drury, V. Ragone, G. Ottcnenelli, E. Buimovici— Hem,M.Ofle,W.Hn§e,J.umms,R.th Thirty—nine patients, 38 with CDC defined AIDS and 1 with ABC were treated with 1.75 ng. qhs of naltrexone, an oral opiate antagonist, in a double blind placebo controlled study. The naltrexone group showed a significant drop in pathologically elevated levels of serum alpha interferon ccnpared with the placebo patients (p'<.01). The double blind phase was ended at 3 nnnths, and placebo patients were given naltrexone. Of 89 patients on naltrexone, 23 showed a worked decline in alpha IFN levels (from means of 144 i.u. to 11 i.u.) over a 12-month period. Sixteen patients showed sustained alpha IFN elevation. Accordingly, a patient classification of responder vs nonresponder was estab— lished. During the course of the study, the 23 responders experienced signif— icantly less 0.I's than the 16 nonresponders (p¢:.01). There were 8 0.I.'s in the responder category and 19 0.I.'s in the nonresponder category. Of the 8 0.1.‘s in the responders, 4 were mild episodes of P.C.P. Three of these 4 episodes occurred before the patient's alpha IFN level had decreased from the adnission level. All of the other 23 0.I.'s in both groups were life threat— ening and in fact, 17 were fatal. In addition to the significantly higher rate of 0.1-. occurrences in the nonresponder group, there was also a signif— icantly higher death rate. As of Decenber 17, 1986 there were 13 deaths (81%), in the group of 16 nonresponders and 4 deaths (17%) in the group of 23 responders (p<:.01). No side effects were noted. wp'zzs Response to therapy in 50 patients with HIV—related thrombocyto- penic purpura. Eric OKSENHENDLER”, P. BIERLING", L—J. COUDERC“, P—M. GIRARD*", M. SELIGMANN‘,I J-P. CLAUVEL“. ': Hépital Saint—Louis, ": Hfipital Henri Mondor. ***: Hfipital Claude Bernard, PARIS, FRANCE. Fifty adults (43 males and 7 females) with serum antibodies to HIV were treated because of profound chronic thrombocytopenia with clinical bleeding in all but two cases. These patients included 25 intravenous drug addicts, 22 homosexual men, 2 transfused patients and 1 hemophiliac. None had full blown AIDS ; 20 had persistent generalized lymphipenopathy and 5 splenomegaly. Mean (: SE) platelet count was 14:2.10 /1 (range 2 to 48). Thirty of 40 tested patients had elevated platelet—bound IgG levels and 11 of 23 had antiplatelet serum antibodies. Lymphogyte count was below 1 SOD/mm in 28 patients and T4 cell count below 400/mm in 20 of 46 patients. Prednisone (1 mg/Kg/day for at least 1 month) was given to 81 patients. A responsg occured in 19 cases with platelet count > 100.10 /1 in 9 and > 50.10 /1 in 10 oth. s ; 6 patients sustained their response off steroids. Three of 21 patients sesponded to danazol therapy (600 mg/day for 6 weeks). Fifteen of 21 patients receiving high dose intravenous IgG (0.4 g/Kg/day for 5 days) responded and 6 of them could be maintained upon repeated boosters. Nine patients received anti-Rhesus immunoglobulin infusions (l 000 pg/day for 2 days of anti-D IgG in 7 Rh+ patients or anti—c IgG in 2 Rh— patients. A partial response occured in 6. Splenectomy was performed in 20 patients and was successful in 16. In our experience, it was the best treatment for patients with severe and symptomatic thrombocytopenia. During a mean follow— up of 16 months (range 4 to 46) one patient developed AIDS (15 months after the diagnosis of thrombocytopenia). 148 wnzzg IMMUNOMDDULATION with BESTATIN in a Double-Blind Controlled Trial with HIV-positive Homosexual Men. MERETE HERDING: I.C.Bygbjer ,P.C.Gntzschd§ K.Bertfi L.Dslh Christensefit V.Faber‘ et 319'Department of Infectious Diseases Rigshospitaleffilnstitute of Medical Microbiology, The State Serum Institute , Copenhagen, Denmark. Bestatin has previously been used to stimulate the cell mediated immune re- sponse in immunodepressed cancer patients. In this study we investigated the effect on immunological, haematological and biochemical variables in HIV—posi- tive homosexual men. 9 22 subjects with PWM‘So‘3é of normal and/or T—helper cell count (0,6 10 /l, but without any opportunistic infections according to the CDC definition of AIDS were treated with bestatin capsules 60 mg daily or placebo for 4 weeks. The immunomodulating effects were evaluated by lymphocyte transformation tests, T—cell subsets, natural killer cell activity, in vitro alpha-interferon production, change in HIV antigen titre and basophil histamine liberation. Values were measured before treatment and a weeks and 10 weeks later. Full results will be presented at the conference. wpzao Gastrointestinal (GI) Non—Hodgkin's Lymphoma (NHL) in Patients (pts) ' at Risk for Acquired Immunodeficiency Syndrome (AIDS) MARGARET DUGAN, C. ODAJNYK, D. KNOWLES, B. RAPHAEL, J. WERNZ, Rita and Stanley H. Kaplan Cancer Center, New York University Medical Center, New York, NY. At our institution 89 cases of diffuse aggressive NHL occurred in AIDS-risk pts since 1981. Of these, 15 male pts (14 homosexual, 1 IVDA) were diagnosed (dx) with GI NHL. Pathologic type was diffuse large cell, immunoblastic plasma- cytoid (6) and diffuse large cell noncleaved (9) or by Rappaport classification diffuse histiocytic lymphoma (15). Concurrent CMV was evident in 2 biopsies and Kaposi's sarcoma (KS) in one other. Median age was 37 years (31-45). 5 pts(33%) had prior AIDS (3 opportunistic infection (01), 2 Ks) and 10 pts (67b) had NHL as their initial manifestation of AIDS. Of the latter 10, 5/5 were (+) for HIV antibody. of the 5 not tested, 2 had prior ARC and 3 were only known to be in an AIDS-risk group. 4 pts (27%) had a concurrent OI at dx of NHL.Sites of pri- mary disease were stomach (3), small bowel (6), large bowel (1), rectum (2)and perirectal mass (3). Median LDH at dx was 303 (164-1521). Clinical staging showed: stage I — 8 pts, Stage II - 2 pts, Stage III - 2 pts and Stage IV - 3 pts. 12/15 had B symptoms. Treatment (rx) of pts has varied including surgery and combination chemotherapy (3), combination chemotherapy alone (8), surgery alone (1) or radiation therapy (1). Median survival is 16 weeks (w) with 8 pts dead, 6 alive (7,8,16,17,18,27 w) and 1 lost to follow up. Because of the indi— vidualized nature of rx regimens employed, no overall conclusion can be drawn regarding response to rx. In conclusion, GI NHL occurs in a subset of AIDS-risk pts as their initial dx of AIDS presenting as local regional disease. NHLshould be considered in AIDS-risk pts with abdominal/rectal symptoms or GI ulcers even with documented 01 or viral GI infection. Despite its early stage at presenta— tion, this subset of extranodal NHL has a poor prognosis and warrants aggres- 51ve rx. WP231 Oral Gancileovlr‘:l Human Phnmaggkinetica and 1:012:1an a ' Mark A. Jacobson , P deHiranda , D.M. Cederborg , E Cobb , HR Brodie*, J Mills UCSF School of Medicine and S.F. General Hospital, San Francisco, CA., ' Burroughs Wallcome 00., Research Triangle Park, NC. Ganciclovir (DHPG, BH759U) is a nucleoslde analog which inhibits herpes viruses in vitro, and which has been effective in treating severe cytomegalovirus (CMV) infection in immunocompromlsed patients. To date, the drug has been administered only intravenously. A: most patients with AIDS and severe CMV disease have required lifelong daily suppressive ganclclovlr (GCV) therapy to control disease progression, oral therapy would appear to have practical advantages. we studied the pharmacokinetics of orally administered GCV ln 4 patients with AIDS and CMV retinitis. Reponted oral GCV doses (10-20 mg/kg every 6 hours) were well-tolerated. with a 10 mg/kg dose given every 6 hours, mean steady-state peak (Cmox) and trough (len) plasma levels were 2.01 uM and 0.87 uM, and the AUG _ b was 33.6 uH.hr. With a 20 mg/kg dose given every 6 hours, mean Cmax Ind SmEn were 2.96 um and 1.05 uM, and the AUG _24 we: 47 uM.hr. Based on urinary excretion and blood levels, calculated agsorptlon was b.51 of the 10 mg/kg q 6 hour dose and 3.0% of the 20 mg/kg q 6 hour dose. The low blood level: achieved make it unlikely that oral GCV therapy will be effective for acute treatment of CMV infections. However, with the 20 mg/kg dose, the mean Cmax exceeded the ED of most clinical CMV isolates, and the mean len level was 5 times higher than that typically obtained with daily intravenous GCV maintenance therapy. Despite its limited bloavnilnblllty, orally administered GCV should be studied to determine whether it will be useful for long term suppressive onti-CMV maintenance therapy in AIDS patients with severe CMV disease. WEDNESDAY, JUNE 3 VVE232 The efficacy of stress management in reducing.high risk behavior and improving immune function in HIV antibody positive men. THOMAS J. COATES and LEON MCKUSICK, University of California, San rancisco, c 001 of Medicine This study was conducted to test the hypothesis that stress mana- gement training for HIV antibody positive men would result in (1) lower stress and depression, (2) decreased high risk sexual behavior, and (3) improved immune function. Sixty gay men, who were positive for antibodies to HIV but otherwise healthy except for lymphadenopathy, were randomized to treatment of wait-listed control groups. Treatment 55 were given an 6-week stress manage- ment program which included training in the relaxation response, strategies for coping with being antibody‘positive, strategies for coping with relationships, strategies for coping with common stressors, and motivation for health habit change. Dependent measures included scales to assess stress and depression, reports of sexual behavior during the month prior to assessment, WBC, T-Helper and T-Suppressor enumeration, and measures of immune function(NK Activity, Lymphocyte Response to Mitogens, Lymphocyte proliferation to antigen). The stress management intervention was effective on several dimensions. We found no differences between treatment groups at baseline. At posttest, the treatment group reported significantly less stress and depression than control 55. Treatment 85 also reported significantly lower rates of sexual behavior capable of transmitting HIV. We also found significantly higher levels of NK activity and response to mitogen in the treatment Ss. WE233 Inactivation of the Human Immunodeficiency Virus by Neutral Buffered Formalin and Quaternary Ammonium Compounds. LINDA S. MARTIN, S.L. LOSKOSKI, W.W. BOND, Centers for Disease Control, Atlanta, GA. Because persons working in pathology laboratories have expressed concern about the survival of the human immunodeficiency virus (HIV) in tissues fixed with 10% neutral buffered formalin (NBF), we evaluated this reagent's effect on HIV survival. HIV preparations (LAV prototype strain) with ID—SO titers 2 105 were rendered undetectable in the ID-SO assay by treatment with IX (12 NBF - 0.37-0.41 formaldehyde) or greater NBF. We also tested effects of quaternary ammonium coumpounds (gusts) on virus viability. The three quets tested--a double quat, a twin-chain quat and a single chain quat--eithet alone or in combination constitute virtually all commercial products marketed in the United States. In our test system all quats were capable of inactivating HIV (effective concentrations ranged from 500 to 1000 ppm) further demonstrating HIV's sensitivity to a spectrum of disinfectant chemicals. WP.234 Development of a Simple Clinical Method to Screen for AIDS Virus in Blood Donors in Underdeveloped Countries. J. ALLEN MCCUTCHAN, M. KLAUBER, C. KENNEDY, S. KLAUBER, P. SPECHKO, D. JACOBSUN, et a ., University of California, San Diego, San Diego. CA. A low-cost clinical method for determining AIDS virus (HIV) positive blood donors is needed to control the spread of AIDS via blood transfusions in underdeveloped countries. In many areas of the world cost precludes the use of antibody screening tests. Using a San Diego population of 159 healthy gay men of whom half were HIV antibody positive. three simple clinical tests were used in a logistic model to detect seropositive men: hematocrit, number of enlarged (>1 cm) cervical lymph nodes and number of non-inguinal regional sites with enlarged lymph nodes. This 3-factor model yielded a test with 91% sensitivity and 62% specificity. Addition of more expensive or more complicated predictors made only slight improvement in test performance. A simpler model which excluded hematocrit and utilized only the examination of lymph nodes maintained sensitivity (90%), but was less specific (42%) and thus. would exclude more uninfected donors. Even at the high seroprevalence (18%) currently reported in blood donors from some African cities (Lancet 1986giizlll3). the predictive value of a negative test for the 3-factor model is 97% and for the 2-factor model is 95%. Deployment of these tests requires that they first be validated in the popu- lation in which they are to be used because sensitivity and specificity of the test may differ between populations and observers. We conclude that a simple. low-cost clinical exam may provide a means to screen blood where cost precludes use of currently available antibody tests. 149 WP235 Sumary of a StatewideProgram to Identif .Blood Donors Infected ' with Human lmmunodef1c1ency Virus (HIV): innesota, USA. KRISTINE L. MACDONALD*. S.J. SCHLETTY*, R.J. BONMAN**, H.F. POLESKY***, . . , M. . ERHOLM*, *Minnesota Department of Health, Minneapolis, MN, **American Red Cross Blood Services, St. Paul, MN. and ***Memorial Blood Center, Minneapolis, MN, USA. HIV antibody screening (with Western blot confirmation) of blood donors began in March 1985 in Minnesota. Follow-up of infected donors can provide useful public health information. We report here the results of a statewide program sponsored by the MN Dept. of Health to identify HIV-infected donors Approximately 400,000 donors have been screened in Minnesota for HIV antibody. To date, 15 state residents who have antibody to HIV have been identified. 14 are male and I is female. The mean age is 30 years (range, 20 to 39L 36 patients in Minnesota received blood from previous donations from these donors; 3 of 15 recipients without other risk factors (20%) were determined to be HIV antibody positive (14 others are known dead and 7 have not been contacted). To date. interviews have been completed for 12 donors (all male). Risk factors were identified for 11: 10 are homosexual or bisexual, and 1 had sex with a female prostitute. For homosexual or bisexual men, the mean number of male sexual partners since 1977 is 20 (range 1 to 50L When asked why they had donated blood, 8 indicated that they did not perceive they were at risk for acquiring HIV infection, 2 felt peer pressure to donate blood and 1 wanted to know his HIV antibody status. Our results indicate that most HIV antibody positive blood donors in our state have known risk factors for acquiring infection and that lack of (or denial of) perceived risk is the major reason that persons in high-risk groups continue to donate blood. wnzss Confirmation of Antibodies to HIV Prior to Donor Notification of Test Results: The New York Blood Center Approach. 9. BIANCO, B. HOSEIN, A. WALDMAN, J. VALINSKY, V. MALAVADE, and J. PINDYCK, The New York Blood Center, New York, N.Y. 10021. Despite improvements in the specificity and sensitivity of ELISA screening assays for antibodies to HIV, high frequency of false positives warrants performance of additional assays prior to donor notification. The most accepted is the Western blot (WE), a research test without uniform criteria for interpretation which in some instances produces uninterpretable results. We have found strong positive correlation between WE positivity and absorbence in the ELISA assay for two commercially available tests. WB positivity is low at low ELISA absorbsnce ranges and approaches 100% at high ranges. However, some samples are NB positive in the low range, and others are negative in the high range. To address these inconsistencies we used additional assays such as the indirect immunofluorescence (IFA) and ELISA based on different antigenic preparations. Analysis of results generated a decision tree for confirmatory assays: (a) WE negative in the low absorbance range or positive in the high absorbsnce rangeis accepted as a true result; (b) all other samples are subjected to additional confirmatory assays. The majority of the individuals found to be antibody positive returned for test repeat, notification and counselling. Results indicated that the initial decision was correct in all cases. Studies of helper and suppressor T cells shawed that 60% of these individuals had ratios below one, suggesting alterations of immune function. WP237 Looking Forward: The Challenge of Iookback S.SAMSON*, M.BUSCH*, JAMMEER*, D.DEITCH*, J.WARD**, x.pEnKINS*; *Irwin Memorial Blood Bank, San Francisco, CA; **CDC, Atlanta, GA The vast majority of high-risk donors self-excluded prior to anti—HIV test Iicensure, and thus are not presenting to blood banks and triggering lookback. This is evidenced by extrapolation from the progressively declining seropre— valence rate over the first two years of the testing (0.3% to 0.03%), and our experience with an expanded lookback effort. As of January, 1987, prospective screening has identified 32 HIV-positive donors with prior donation histories, which has resulted in notification of only 200 potentially exposed recipients. Our broader program has been triggered by two additional events: active identification of reported AIDS patients with a history of donation, and active investigation of reported transfusion—transmitted HIV infections. Of 139 AIDS patients who donated blood at Irwin Mennrial Blood Bank since 1977, only 10% were reported as such by local health departments; the remainder were identi— fied by active cross-referencing of AIDS case listings with donor records. These 139 AIDS patients donated blood to ca. 950 people (53/106 tested reci— pients are HIV+), 28 HIV+ high-risk donors found while investigating 50 TAA cases has led to notification of an additional 322 potentially infected reci- pients thus far. Recipient testing of each group showed that 50% of traced recipients were infected. Although our broader lookback efforts result in 7 fold greater notification over standard prograns, it is unlikely that even this program is tracking the majority of exposed recipients. WEDNESDAY, JUNE 3 WE238 CLINICAL OUTCOME or HIV INFECTION IN HAEMOPHILIA UNI. DEPT OF MEDICINE GLASGOW ROYAL INF SCOTLAND. RAJAN MADHOK JA GRACIE GDO LOWE CD FORBES The outcome of HIV infection in Haemophilia is not clear. One US study showed a 131 3 yr. incid. of AIDS (SCIENCE 231992-5). No similar studies are available from elsewhere. We report on the clinical immunological outcome of 23 HIV antibody positive haemophiliacs followed since seroconversion mean :49.5 mths range 24—66. One patient is lost to follow up but is known to be alive. No patient has developed AIDS but i Pta. has had recurrent bacterial infections. 1 pts. oral candida. Specific manifestations of HIV infection include thrombocytropenia in 1 pts. episodic lymphadenopathy in 3 pts. The total lymphocyte cnt fell over 3 yrs. A11 pts. had a TA lymphopenia median A23 range 321-734. The TA cnt in early seroconverters (Z 50 mths.) was no different from late seroconverters but in individual pts. th I A cnt fell significantly (p: 0.05 prd wx test). The results of this cohort confirm the previous finding of a lower risk of AIDS in haemophilia. (SCIENCE 231 992-5) relative to other risk groups. Factors other than time may influence the decline in T4 cell numbers. WBZ39 Immunological Alterations Unrelated to HIV Infection in Transfused Children with Sickle Cell Disease NAOMI L.C. LUBAN*, A.E. NILLIAMS**, M. SULLIVAN**, G. REAMAN‘, *Children’s Hospital National Medical Center and **Jerome H. Holland Laboratory, American Red Cross, Washington, D.C. and Rockville, MD. USA Immunological abnormalities similar to those seen in AIDS have been reported in adults and children with sickle cell disease (SCD) receiving chronic RBC transfusion. The extent to which these abnormalities develop in the absence of HIV infection is unknown. He have performed longitudinal serological and immunological evaluations of 20 transfused children with homozygous SCD from 1983 to 1986 to determine the frequency of immunological alterations over time. Seven children (2-16 years) receiving sporadic transfusion (STX), and 13 children (9-16 years) receiving chronic transfusion (CTX) were studied. The mean numbers of transfusions received prior to the first assessment of the STX and CTX groups were 5.9 and 90.7 respectively. The second assessment was done from 25 to 44 months following the first. The groups received a mean of 4.5 and 79.7 transfusions respectively during the study interval. No correlation was observed in either group between the transfusion load and 0KT3, 0KT4, or 0KT8 numbers, 0KT4/0KT8 ratio, and serum levels of total lg or beta~2 microglobulin. Four of the 13 STX children experienced absolute OKT4 reductions of greater than 85% over the study interval. Three of the seven CTX patients experienced absolute T4 reductions of greater than 50%. All other children remained normal. One CTX patient with a 51% reduction in T4 count seroconverted to HIV. All other patients were HIV—EIA negative, although four demonstrated reactivity to HIV/p24 by Western blot. Our data suggest that no consistent immunological abnormalities are produced by large numbers of RBC transfusions over time, but that T4 lymphopenia not directly attributable to HIV may occur in selected children . WB240 THE EFFECTS ON THE DONOR BASE OF A NATIONWIDE SCREENING PROGRAM FOR THE PREVENTION OF TRANSFUSION ASSOCIATED HIV INFECTION J.B. Derrick, S. Mankikar, M.G. Davey, Canadian Red Cross Blood Services, National Headquarters, TORONTO, CANADA Maintaining an inventory of the safest possible blood and components while maintaining an adequate donor base has been a continuing challenge ever since the possibility of transmission of AIDS by blood was recognized. Through the implementation of nationwide, standardized donor and donation screening procedures the Canadian Red Cross has, however, been able to essentially eliminate the threat of HIV infection through transfusion with no significant impact on the donor base. Donor screening includes obligatory reading of an information pamphlet, individual interviews with options to exclude use of possibly infectious units, laboratory testing of donations by enzyme immuno- assay (EIA), discard of repeatably EIA reactive donations, and confirmatory testing by Western blot (VB). Donors are forewarned that a positive test means that they will be permanently deferred from donating, that they should consult their doctor and that, where required by law, their anti-HIV status will be reported to regional health authorities. Nevertheless, donations during the first year of anti-HIV testing increased over the preceding year by 2%. The incidence of repeatably reactive donations was 0.3% and some 95.6% of these could not be confirmed by "B. A follow—up study of those who return to donate is underway. Preliminary analysis of 377 returnees shows 47.52 tested EIA-lHB—, 342 remained EIA+/WB-, 18% tested NB indeterminate and 0.51 had seroconverted to EIA’IWB‘. A policy for notification of donors who consistently test EIA* end/or NB indeterminate is under development. The data and findings outlined above will be updated on the basis of 15 years experience at the time of presentation. wnz41 HIV Positivity: The Psychosocial Impact of Donor Notification DEBORAH K. DOUGLAS*, M. HARPER*, F. POLK“, American Red Cross Chesapeake Region, and Johns Hopkins Hospital". We began to notify and counsel donors with confirmed positive HIV antibody results in July 1985. In our experience, although the majority of donors from whom a reliable history could be obtained readily admitted to being in a known risk group for HIV infection, 24% denied any history of exposure to HIV. 43% of confirmed positive female donors and 18% of males were thus classified as risk "unknown." All counseled HIV positive donors are invited to participate in a prospective natural history study of HIV infection in blood donors. As part of this study, we administer the Center of Epidemiologic Studies Depression Scale (CBS-D Scale). This scale is a self-administered questionnaire designed to detect both the presence and the degree of depression in study participants. Questions address both affective and physical symptoms. Overall scores range from O to 60, with a score of greater than or equal to 16 indicative of clinical depression. CBS-D data is presented for the first 48 HIV positive donor subjects, as performed within two months of notification of their serologic results. 38 successfully completed all questions, and 45% had scores 1 16. Donors who acknowledged risk activity of HIV infection had higher scores (mean = 21) than donors who acknowledged no risk (mean = 13) (p < 0.1). We conclude that broad denial mechanisms exist in donors who deny risk for HIV infection. These mechanisms are intact not only when they donate blood but also when they are confronted with evidence of infection. Such denial will complicate donor notification, counseling and recommendations for behavior modification to prevent further transmission of HIV in this population. WP242 Diagnosis of HIV Exposure With a Competitive Enzyme Immunoassay ' (CIA) for Antibody to the Transmembrane Envelope Glycoprotein (gp41) of Human T-Lymphotropic Virus, Type III (HTLV-III). J. SCOTT NEBBER, G. J. DANSON, J. C. HUNT. R. G. ALLEN. E. CHAN. R. H. DECKER. et al.. Abbott Laboratories, North Chicago. IL. Conventional ELISA techniques have proven extremely useful in removing HIV infectious units from the blood supply. We have developed a specific and sensitive two-step competitive inmunoassay (CIA) that utilizes a recombinant DNA derived full length p41 protein and a monoclonal antibody to detect antibodies to the transmembrane envelope glycoprotein (gp41). To show the reliability of anti-gp41 as an indicator of HTLV-III (HIV) exposure, we tested sera from patients with acquired inmunodeficiency syndrome (AIDS), AIDS related complex (ARC), asymptomatic patients. and blood donors that were identified as seropositive by conventional screening ELISA and by Western blot. All samples tested were reactive using the recombinant p41 based CIA. To quantitatively compare sensitivity between Hestern blot and CIA. serial 2-fold dilutions of eleven patient sera (5 AIDS. 3 ARC, 3 asymptomatic) were tested. The CIA proved to be three to six 2-fold dilutions more sensitive than Western blot when scoring for gp4l. In addition, early antibody response to HIV in seroconversions was detected by the CIA in samples nonreactive or weakly reactive with conventional screening tests and/or Western blot. These data indicate that antibody to gp41 is a highly reliable and consistent marker for HIV exposure throughout all stages of the disease. HOW SAFE WAS (AND IS) BLOOD TRANSFUSION IN SYDNEY, AUSTRALIA. WEZ43 ARCHER GT, BOLTON W, COOK LA, COULITS T, KENRICK KG. LEARMONT J. New South Hales Red Cross Blood Transfusion Service, Sydney, Australia. 72 cases of post-transfusion HIV infection in patients other than haemophiliacs have been reported and or traced by the Blood Transfusion Service in Sydney to the end of January 1987. 20 of these patients have developed AIDS (16 deaths), 16 have lymphadenopathy, the remainder have no symptoms. HIV infection has resulted from transfusion of whole blood, red cells, platelets and plasma. Follow—up studies have shown an extremely high risk of HIV transmission from all donations made subsequent to implication of that donor in a known case. The number of donors who have been proven anti-HIV positive in look-back studies to date stands at 27; 18 of them have baen responsible for transmission of the virus in 32 cases. The risk of HIV infection increased progressively from 1 to 85,000 per unit transfused in 1980 to I in b.000 in 198A. No case has been reported in patients transfused since routine screening for HIV antibodies commenced in Australia on I Hay 1985. WEDNESDAY, JUNE 3 wnz44 Conparative Detection of anti—HIV in a Seroconverting Blood Donor ,.G E. m1m*, D. W“, *Boston Bio- medica, Inc., Mansfield, MA, “Calamity Blood Center of Greater Kansas City, Kansas City, ID, “*Electro—moleonics, Inc., Colunbia, MD Plasma drawn from a male twosexual at weeks 0, 9, 12, 15, 17, 18, 19, 20, and 23 (1981) was tested (1987) for anti—HIV by seven FDA licensed ELISA proce- dures, an unlicensed ELISA (Abbott: Envacor), Western Blot (W8), and IFA, as well as for HIV antigens by an experimental antigen-capture assay (Electro- moleonics), and for antibodies to 5-9 cellular antigens. Cne licensed ELISA procedure (Organon 'Ileknika: Bio-EmaBead HILV III) de- tected anti-HIV at 12 weeks; the other six first detected anti-HIV at week 15. Signal to cutoff (s/co) ratios consistently increased following initial reac- tivity. With Envacor, anti-gp41/160 was detected at 12 weeks; anti-p24/55 at week 18. By WB, anti-1324 first appeared at week 15, followed by anti-gptl at week 18,- anti—p31 was never detected. With IFA, the 15 week and stbsequent specimens were reactive. Antigen-capture assay detected HIV antigens at week 12 only; antibodies to li-9 antigens were never detected. . These data suggest I) in anti-HIV seroconversion, HIV antigens are tran- siently serologically detectable, suggesting the presence of infectious virus, 2) anti—HIV can be detected by sensitive ELISA concomitantly with the first de- tection of HIV antigens, obviating the need for HIV antigen tests in current blood bank screening, 3) repeatably positive ELISA reactions with IPA/W8 nega- tive or WB p24 positive only results nay represent early seroconversion; thus, follow-up studies are essential, 4) in sequential sanples, consistently in- creasing s/co ELISA ratios, positive IPA results, and the emergence of anti- bodies to additional HIV antigens in WE are indicative of seroconversion, thus confirming infection, 5) current ELISA procedures have end-point sensitivities equal to IPA and WE, except Bio-ErxzaBead which appears slightly more sensitive. WP245 Importance of T Cell Subset Determinations in Heavily Treated, Se— vere Hemophiliacs SHELBY L. DIETRlCH*, D.C. BOONE**, J.W. PARKER“, *Hemophilia Treat— ment Center, Orthopaedic Hospital, Los Angeles, CA, **USC School of Medicine, Los Angeles, CA. A retrospective study was undertaken to determine correlation between T cell changes and clinical outcome of patients with severe A or B hemophilia. 186 pa— tients were followed from 1983 through 1986 with serial determinations of lympho— cyte subsets and white cell and platelet counts. The patients were arbitrarily assigned to two groups based on Til cell counts: 46 with less than 400 T" cells (Group I) and mo with more than ‘100 T4 cells (Group 2). Median follow-up times were 17 months for both groups. In Group 1, 10 (22%) developed AIDS, 13 (28%) developed ARC, and I16 (50%) remained asymptomatic. In Group 2, 9 (6%) developed AIDS, 11 (8%) developed ARC, and 120 (86%) remained asympto— matic. When data from the AIDS patients were separated from the groupings, median T-lymphocyte values were: NonAIDS AIDS p 5400 TH Ce 5 21100 Tll Cells lnlfial TH 297 693 322 0.0l Final T0 220 562 103 0.01 The relatively unchanging course of Group 1 subjects may indicate either a long incubation period prior to clinical disease or a relatively high resistance to clinical infection. Subjects who had relatively stable values tended to remain asymptomatic. The T cell counts of the AIDS subjects were characterized by a marked progressive decline. Therefore, serial declines in T cell subsets may be an early indicator of clinical disease. w2246 Evaluation Of HIV Antigens Obtained From Commercial Sources By The Western Blot Technique RONALD C. FITZGERALD, L. A. MOTLEY, J. A. ROKOVICH, K. C. PALLIS, D. GOLDSTEIN, G. B. LAMOTTE , Bio-Rad Laboratories, Clinical Division, 1000 Alfred Nobel Drive, Hercules, CA 94547. HIV antigen preparations consisting of disrupted virus particles are avail- able from several commercial sources and have been used as antigens for de- tection of antibodies. In order to evaluate the relative concentrations of the viral proteins and purity of these preparations, the HIV proteins were separated by the Western Blot technique. The relative amounts of viral and non-viral protein were determined by protein staining and analyzed by reflect- ive densitometry. Immunoreactivity to a panel of patient sera was measured by enzyme immunoassay of the WB strips. With many of the commercial HIV antigen preparations, the majority of the proteins did not migrate at positions cor— responding to immunoreactive viral-specific proteins and glycoproteins. Large amounts of protein were found at 70,000 Daltons and/or less than 18,000 Daltcns. With some preparations, these contaminants reacted with ELISA nega- tive sera samples to give faint bands. With some preparations a weak non- viral band was also noted at a position corresponding to the viral major cap- sid protein p24. These contaminants could confuse interpretation of HIV negative ears. The amount of protein migrating at particular band position did not necessarily reflect the potential immunoreactivity. This was most evident for high and low molecular weight regions. The highly immunogenic gpléO/gplZO were often barely detectable or non-existent in some preparations by immunoreactivity. These studies emphasize the importance of careful eval— uation of the purity and immunoreactivity of each commercial HIV antigen by WB analysis for diagnostic and analytical purposes. ' 151 WP247 Studies of Normal Donor Specimens Causing Various Reactivity Patterns in Sensitive Western Blot Assays. PETER L. TAN, J. W. D. KAY, and D. MUNJAL, Organon Teknika Corporation, Durham, NC. Western blot (Wb) has become a valuable technique for demonstrating the anti— body fingerprint of a particular serum to the antigens of HIV. However, as has been recognized, there are many Western blot assays being used currently with variations in virus preparations. blotting techniques, reagents and in- cubation conditions, visualization techniques and standards for acceptability. Recent attempts to use a very sensitive Western blot test to evaluate speci- mens from the clinical evaluation of the improved Bio-EnzaBead HTLv-lll ELISA test system indicated that there were normal donor specimens having a variety of reactive bands. primarily in the p17, p24, p53 and p66 regions. However, periodically there was some reactivity in the gp41 area, but the banding was more restricted and not the characteristically diffuse zone, and repeated runs of the same specimen would not yield reproducible detection of bands in the gp41 region. Two specimens that appeared to have this type of nonreproducible gp41 reactivity were analyzed with a sensitive lFA technique used by the San Francisco Department of Public Health (J. Wilber); both were nonreactive even at a 1:3 dilution. Adsorption of the sera with a T-cell line followed by Western blot showed elimination of reactivity; the major reproducible band seen is to the p24 region, and this was completely eliminated. These results would caution that the use of very sensitive Western blot tests for evaluation of normal donor specimens may require multiple blot tests and/or possible adsorption: in order to indicate significant reactivity in Western blot. WE248 TRACING 0F SEROEOSITIVE BLOOD DONORS T0 ASSESS THE PRESENCE OF *RISK FACTORS G. IPPOLITO , P. ANGELONIM , E. MANNELLA* , C. A. PERUCCI Latium Region Epidemiologic Unit, National Center for Blood Transfusion— Italian Red Cross; -Rcme, Italy Starting from 1963 National Health Services and blood bank associations made recommendation that members of risk group for AIDS should refrain from blood donation, to reduce the risk of infection associated to the administration of infected blood. Nevertheless after the availability of screening tests for anti HIV antibodies, person at increased risk for AIDS started to donate blood to have a ascertain their immunologic status versus HIV infection. In Latium Region screening of blood unit for anti HIV antibodies is mandatory starting from 1985. Prevalence of seroposltivity, Western blot confirmed is .0006. To evaluate the risk factors of seropositiva blood donors and compliance to the self-exclusion programmes all seropositive subjects from National Transfusion Center of Italian Red Cross were contacted. From March 1985, 89113 blood donors have been tested. 228 were repeatable seropositive to screening tests and 53 confirmed by WB. 42 out of 53 seropositive have been traced. Of These 5 (11.9%) were intravenous drug addicts (IVDA), 21 (50%) IVDA in the past, 6 (14.31) partners of a IVDA, l (2.AZ) homosexual and IVDA, 3 (7.11) homosexuals, 3 (7.1%) promiscuous heterosexuals, 2 (b.81) not Known risk factors. This result evidences that the alternative sites availability, free of charge in Italy, for anti HIV testing and predonation appeals to refrain from donating plasma and/or blood are not effective in dissuading subjects at risk. Mass campaigns and more extensive pre-dcnation counselling and medical examinations are needed to avoid the risk increase of transfusion associated infections. wP249 Prospective follow—up of transfusion-associated acute HIV infection 31 ESTEBAN,J GENESCA,JM HERNANDEZ,L MASSUET, JWK SHIH,HJ ALTER, et a1 Hospital Vall d'Hebron, Barcelona,Spain and Dept.Transf.Medicine, National Insti— tutes of Health, Bethesda,MD. To identify recipients during the acute phase of TA HIV infection, 4,725 donor samples, collected in Barcelona during the 2 months prior to routine screening, were tested for anti—HIV by EIA.Of the 4 units positive by EIA and WE, only 3 had been transfused to 4 recipients.of these,2 were dead at the time of identi- fication,1 could never be contacted and 1 has been prospectively followed since posttransfusion week 4. This recipient,a 54—year old woman who received 1 posi— tive unit of PRC5 during breast cancer surgery, is currently undergoing weekly plasma and lymphocyte-pheresis.Results on initial evaluation of HIV-antibody, HIV-antigen (using commercial kits) and T-cell subsets are shown in the table. WEEKS POSTTRANSFUSION 4 5 6 7 8 9 11 12 HIV-Ab EIA 1:2* 1:2 1:2 1:1 1:1 1:1 1:2 1:8 HIV-Ab WB p160 + +/- +/- — - - + ++ p41 — — — — — — +/— + p24 — — - +/- + ++ +++ +++ HIV—Ag EIA + — — — - — - — T4 (cells/mm ) ND ND NA 213 850 452 926 983 T8 ” ND ND NA 2,671 1,175 1,006 964 1,109 T4/T8 ND ND NA 0.07 0.7 0.4 0.9 0.8 ND:Not done; NA:cells not available;*end-pcint dilution No clinical symptoms or physical abnormalities have been detected during follow up. Attempts to recover the virus from cryopreserved lymphocytes and plasma,cha— racterization of early morphological and functional changes in PBLS and Search for neutralizing antibody in sequential samples are currently under way. WEDNESDAY, JUNE 3 WP.250 Anti-HIV IgM Screening in High—Risk Subjects G. BEDARIDA*, P. CROCCHIOLO*, GIUSFIPPE CAMBIE'*, F. D'A— GOSTINO*, I. ARCIDIACONO*, M. PASOUALI**, et a1.,*Ospeda1e Maggie- re, Lodi, Italy, **Istituto dei Tumori, Milan, Italy. Most of the tests developed for the screening of HIV antibodies are aimed at HIV—IgG, only a few at HIV-IgM detection, while com— petition tests theoretically should be able to evidence both clas- ses of immunoglobulins. Sixty-five parenteral drug-addicts (PDAs) and 123 polytransfused subjects, all resulting HIV-IgG negative by different commercially available tests, were investigated for the presence of HIV—19M also by a modified ELISA method which we deve- loped to make it more specific and sensitive for Ing (Tech IgM HTLV III, Technogenetics, Torino, Italy). According to this 5 out of 65 HIV~IgG negative PDAs (7.7%) were found HIV—IgM (WB-IgM con- firmed) positive; IgM positivity was also evidenced in 3 polytrang fused, HIV—IgG negative subjects. IgM—IgG switch was shown in 4 out of 5 PDAs 1 to 38 weeks (mean 19 weeks) after the first IgM-pg sitive result. In the 3 HIV-IgM positive polytransfused subjects, for each of whom an HIV-positive donor was traced, 1914 appeared ap- proximately 12 weeks after transfusion and, in 2 of them, IgM~IgG switch occurred after another 8 weeks. In all subjects examined, HIV—19M, representing the earliest sign of infection, were detected by our test (WB—IgM confirmed) at least some weeks before this could be done by other methods, including competition tests. 152 Plenary Session V The Human Immunodeficiency Viruses: I987. TH.1.1 Luc Hontagnler, Institut Pasteur, Paris, France. ABSTRACT NOT AVAILABLE AT TIME OF PRINTING TH_1_2 Human and Simian T Lymphotropic Retroviruses: Serologic Identification and Vaccine Development. M. ESSEX‘, P. KANKI*, R. MARLINK', S. M'BOUP**, F. BARIN'**, F. DENIS;;;‘, et al., *Harvard School of Public Health, Boston, MA, **Dakar University, Dakar, SENEGAL, ***Univ. Bretonneau, Tours, FRANCE, *"*Univ. Dupuytren, Limoges, FRANCE. Retroviruses related to HIV have been detected in subhuman primates where up to half of the wild-caught African green monkeys have serologic evidence of exposure to such viruses, designated STLV-3. Following natural exposure monkeys rarely, if ever, develop disease. Using seroepidemiological approaches, healthy people in West Africa were found to be exposed to viruses that are closely related to STLV-3, and designated HTLV-4, LAV-Z, HIV-2, SBL-6669, or West African retroviruses (WAR). In some instances such viruses are found in individuals with AIDS-like illnesses. However, seroepidemiological studies did not reveal an association between antibody positivity and disease development. Infection rates vary widely for different geographical locations in West Africa, but Central Africa seems free from exposure to this virus. HTLV-4 type viruses are transmitted primarily by sexual contact as illustrated by elevated infection rates in female prostitutes. Yet infected prostitutes generally remain healthy and free of lympha- denopathy. Understanding why infection with STLV-3 or HTLV-4 does not pose a high risk for AIDS should be important to determine how to generate immunity in people exposed to HIV. TH.1.3 LENNART NETTERBERG, ANDERS SUNNERBORG, the Karolinska Institute, Stockholm, we en. The central nervous system (CNS) effects of human inmunodeficiency virus (HIV) has recently been acknowledged. CNS involvement may be monitored using psychological testing, computer tomography and magnetic resonance (MR) imaging technique. By combining the MR unit with an imaging enhancing technique reconstruction of different brain regions can be made and treatment effects may be followed by measuring the relaxation times T 1 and T 2. New treatments using short peptides such as the octapeptide, peptide T are of interest since clinical testing indicate that it appears non-toxic and may have potential benefit. The working hypothesis is that peptide T, D-Ala—Ser-Thr-Thr- Thr-Asn-Tyr-Thr, inhibits HIV-infection by blocking the binding of the viral envelope to the CD4-receptor. Peptide T is a segment of the envelope glyco- protein (gp-lZO) of the HIV. Neuropathological findings in the brains of patients with AIDS are common and suggest that HIV might induce irreversible damage. There is however a dis- crepancy between the degree of cerebral atrophy and the severity of the CNS symptoms. The new results using reconstructed MR images in patients treated with peptide T suggest that the CNS involvement is at least partly reversible. The methods to test neuropsychiatric dysfunction caused by HIV will be summarized as well as objective measures to follow the presence of HIV in the cerebrospinal fluid. By mimicking the action of peptides, viral proteins could exert hormonal effects throughout the body, including the CNS. and thus may have a role in the etiology of the progressive dementia of patients with AIDS. HIV infection in the central nervous system THURSDAY, JUNE 4 Virology—Related Viruses TH'2_‘| Nucleotide Sequence Analysis of the West-African AIDS Virus, HIV-2. M. GUYADERI, P. sowxcoZ, M. EMERMANI, F. CLAVELI, L. MONTAGNIERI, and MARC ALIZONl. I : U. d'Oncologie Virale, and 2 : UREG, Institut Pasteur, Paris, France. A novel retrovirus, the human immune deficiency virus type 2 (HIV-2, previously named LAV-2), was isolated from patients with AIDS and related conditions originating from West Africa (Guinea Bissau, Senegal, Gambia, ivory Coast ...). This virus is related to HIV-l, the causative agent of AIDS in Central and East Africa, as well as the USA and Europe, by its morphology and by its tropism and in vitro cytopathic effect on CD4 (Til) positive cell lines and lymphocytes, but differs from it by lack of hybridization of the genomes and absence of antigenical cross-reactivity of the envelope glycoproteins. The complete proviral DNA from one HIV-2 isolate (ROD) was cloned, and used to confirm the distant relationship of HIV-1 and 2, this latter being more closely related to a simian retrovirus termed STLV-3 or 51V. Polymorphism is observed by restriction mapping of HIV-2 isolates. We have sequenced the complete HIV-ZRQD genome and observed an overall genetic organization similar to HIV-I. However, the HIV-2 genome is longer (9.6 kb. against 9.2 kb.), mainly because of large insertions in the LTR. The proteins of HIV-1 and 2 are highly divergent, the degree of conservation ranging from 50 96 (for g and pgl) to less than 30 96 of the aminoacids for the large fl glycoprotein, and Q proteins. Homologous domains in $11 will be very useful to delineate domains involved in functions common to HIV-1 and 2, such as cell fusion and T4 binding. TH 2_2 Conservation of genome organization between HIV and STLV-3 VANESSA HIRSCH, NORBERT RIEDEL, HARDY KORNFELD, GREGORY VIGLIANTI AND JAMES I; MULLINS Department of Cancer Biology, Harvard School of Public Health, Boston, MA 02115 Type 3 Simian T-lymphotropic virus (STLV-S) shares many biologic characteristics with HIV, utilization of the T4 molecule as a receptor, syncytia formation in T4-lymphocytes in vitro, similar ultrastructural morphology, Mg+2 dependent reverse transcriptase, major gag-, env-, pol-, and 3'orf—encoded viral proteins of similar size and immunologic cross-reactivity. STLV-3 from African Green monkeys was recently molecularly cloned by virtue of weak nucleic acid cross-reactivity with HIV. Nucleic acid sequence analysis of the 3' 4.2 kb of STLV-3 reveals that HIV and STLV-3 share a similar genome structure. Predicted amino acid sequences of the envelope gene of STLV-3 and HIV share up to 50- 55* homology in regions identified as constant domains of the HIV env gene, and analogous positioning of all of 18 cysteine resi- dues in HIV. This indicates that these divergent proteins likely possess a similar backbone structure. Coding regions previously found to be unique to HIV and shown to encode regulatory functions (tat and art) are preserved in STLV-3, indicating that HIV and STLV—3 likely utilize similar regulatory mechanisms (see Viglianti et al). A high degree of conservation of predicted protein sequence was also noted within the 3'-orf region, whose function is unknown, and in the "R" open reading frame for which no protein has yet been identified. This strongly suggests that both genes play an important role in the life cycle of each virus. TH 2 3 Molecular characterization of HTLV-lo ' ' B. HAHN", S. ARYA**, P. KUHAR", M. TAYLOR*, L. KONG*, S. LEE*, F. WONG-STAAL**, R. GALLO**, G. SHAW". *University of Alabama at Birming- ham, Birmingham, AL; **Laboratory of Tumor Cell Biology. NCI, NIH,, Bethesda, MD. A novel human retrovirus, termed HTLV-h, has recently been isolated from West African individuals at high risk for sexually transmissible diseases. This newly discovered virus is related to HTLV-3/LAV in its tropism for OKTla lymphocytes, the antigenicity of its core proteins, and its in vitro growth characteristics but is clearly distinct from the AIDS virus in its ultrastructure, the size and antigenicity of its envelope proteins, and its apparent clinical sequelae. The existence of these two viruses -- both tropic for OKTA-positive cells yet possessing major differences in protein structure and biologic activity -- provides a unique opportunity to study the molecular biology and structure-function relationships of both HTLV—S/LAV and HTLV-li. We have molecularly cloned the full-length provirus along with unique flanking cellular sequences from two isolates of HTLV-li and have prepared subclones for transfection and for nucleotide sequence analysis. Comparisons between HTLV‘A and HTLV-III/LAV reveal underlying similarties in gene organization (env, 3'orf, and LTR) although overall nucleotide sequence homology is in the range of only 1:02. Interestingly, a peptide sequence from the 3' terminus of the HTLV-III/LAV envelope implicat- ed in its cytopathicity is conserved (12 out of 14 amino acids) in HTLV~14. Structure-function relationships especially concerning the envelope glycoprotein between HTLV-lo and HTLV-III/LAV will be discussed. THURSDAY, JUNE 4 TH 2.4 Molecular Cloning and DNA Sequencing Analysis of LAV—2 pathy Associated Virus Type 2) BRUNO STARCICH, J. F. ZAGURY, S. JOSEPHS, F. WONG—STAAL and R. C. Laboratory of Tumor Cell Biology, National Cancer Institute, NIH, Bethesda MD. A new subgroup of primate retroviruses serologically related to the human AIDS agent, HTLV-III(HIV) has been recently identified. This includes the simian T-lymphotropic virus type III (STLV-III), isolated from African green monkeys, and three human retroviruses, HTLV-IV, LAV-2, SBL6669, from patients of West African origin. These viral agents share similar morphology, recognize the same receptor, (OKT-A) but show different pathogenetic potential. In vitro all but HTLV-IV are able to kill their target cells. In vivo, in their natural hosts, only LAV-2 and SBL6669 appear to be associated with an immunodeficiency syndrome. In order to better define the genetic relationship between this new subgroup of pathogenic viruses and the HTLV-III(HIV) subgroup and to gain insights into their cytopathic mechanism, we have undertaken the cloning and sequencing analysis of an LAV-Z isolate. The virus was isolated from an AIDS patient originally from Senegal seropositive for LAV—Z antibodies. A permis- sive cell line, H9, was infected with the viral isolate. The genomic DNA was extracted, partially digested with the restriction enzyme Mbol and used to construct a lambda phage library. The library was screened using a cDNA probe homologous to the 3' LTR region of LAV—Z genome. Ten positive clones were detected and characterized by restriction mapping. The results show an overall divergence in restriction sites in comparison to HTLV-III(HIV) restriction map. To further investigate the structure of the LAV-Z genome, we have sequenced the entire genome of the integrated form of LAV-Z using the Sanger dideoxy technique. The results of this analysis will be presented. (Lymphadeno- GALLO. Tl! 2_5 Characterization of a Pathogenic Lentivirus From Cattle Which is structurally, Immunologically, and Genetically Related to the Human Immunodeficiency Virus (HIV) MATTHEW A. GONDAIK, M.J. BHAUNt, S.G. M.J. VAN DER MAATENtt, ##NADC, USDA, Ames, Iowa. An infectious retrovirus was previously isolated from leukocytes of a cow with persistent lymphocytoais, lymphadenopathy, CNS lesions, progressive weak— ness, and emaciation (Van Der Maaten et a1., J. Natl. Cancer Inst. 49:1649, 1972). In vitra the virus replicates and induces syncytis in cells derived from various embryonic bovine tissues, including brain. By electron micro- scopy, the virus morphologically resembles HIV and other pathogenic lenti— viruses. This virus, designated BIV (bovine immunodeficiency-like virus), possesses a major protein band of 26 kD (p26) and several smaller and larger virus—specific protein bands by SDS—PAGE. A rabbit antiserum to HIV reacts strongly in immunofluorescence assays to HIV-infected cells and on Western blots with p26 and p24, the major core proteins of HIV and HIV, respectively, but not those of visna or caprine arthritis encephalitis viruses. A competi- tive radioimmunoassay using the rabbit anti—BIV serum and nil—labeled HIV p24 was developed. Consistent with the Western blotting data, disrupted HIV and STLV—III competed equally well with HIV p24 in this assay, whereas other lentiviruses competed poorly or not at all. Molecular clones of BIV proviruses have been isolated from a l library constructed from genomic DNA of BIV- infected cells using a cDNA probe made from BIV viral RNA. These clones hybridize with p01 gene probes made from HIV and visna virus. DNA sequence analysis of the 5’ p01 gene region of HIV has enabled us to construct a phylo- genetic tree elucidating the relationship of HIV to other lentiviruses. CARTERt, T.A. HOSTt, L.0. ARTHURt, and tProgram Resources, Inc., NCI—FCRF, Frederick, MD, T'l.2.6 Immune Selection of Antigenic Variants of Equine Infectious Anemia Virus May Occur Through Elimination of Infected Cells Rather Than Through Neutralization of Cell Free Virions SUSAN CARPENTER, LEONARD EVANS and BRUCE CHESEBRO, LPVD, NIAID, NIH, Rocky Mountain Laboratories, Hamilton, MT The morphological, genetic, and serological relatedness between equine infec- tious anemic virus (EIAV) and human immunodeficiency virus (HIV) has increased interest in understanding the role of variation of EIAV in viral persistence and the host response to infection. EIAV was isolated from peripheral blood leukocytes collected during two, early, febrile periods of an experimentally infected horse. These isolates, referred to as MA-l and MA-A, were shown to be genetic and antigenic variants by RNase T -resistant oligonucleotide finger— print analyses and membrane immunofluorescence of infected cells. The finding that variant—specific epitopes of EIAV were expressed on the surface of infect- ed cells indicated that immune selection of viral variants might occur through immunologically-mediated destruction of EIAV—infected cells. Furthermore, antibody to variant-specific cell surface antigens was detectable prior to the development of virus neutralizing antibody. This suggested that neutralization of cell-free viriona may not be important in the selection of EIAV variants. Biochemical identification of viral proteins expressing variant-specific antigens was assayed by radioimmunoprecipitation (RIP) using detergent lysates of EIAV-infected cells. Early iummne serum, specific for MA-l by membrane immunofluorescence, was found to be broadly reactive by RIP. This apparent paradox indicated that EIA viral antigens exposed in detergent lysatea were highly cross-reactive. whereas viral antigens exposed on the surface of live cells were strain-specific. These data caution against the use of immunoassays which rely on detergent treatment of antigens in looking for strain-specific antibody with potential biological importance in variant selection. 154 Health Care—Patient Care, Attitudes, Knowledge, and Risks Helping Young People Face Death: Resuscitation Status and Outcome I I in First Episode Pneumocystis Carinii Pneumonia (PCP) RITA FAHRNER,M.J. CLEMENT, A. KLINE, J.B. COHEN, San Francisco General Hospital, San Francisco, CA, USA. Since the onset of the AIDS epidemic in 198], ICU use for a group of patients with a uniformly fatal disease has been frequently questioned. Addressing this issue, all first episode PCP admissions at San Francisco General Hospital were reviewed for the last six months of I986 (N-IIS), and DNR choice, ICU use, and outcome (death or discharge) were noted. DNR Status No. Patients ICU Admit Discharge or Death Full code 10 0 I0 0 DNR 55 O 42 I3 Code, then DNR A A l 3 Code status not addressed 46 0 46 0 This pattern of ICU use reflects the added knowledge on the part of the house staff, attending physicians, and patients of the poor prognosis of patients with AIDS requiring ICU admission. with this knowledge, less than 102 of patients chose to be on full code status. Patients should be given the early opportunity to discuss their resuscitation status, and counseled regarding the poor prognosis for PCP patients who require intubation. A multidisciplinary approach to the patient's choice, using medical, nursing, and counseling resources, allows the patient and family to best under- stand the implications of their decision. This decision will become more complex as potentially effective antiretroviral therapy for AIDS becomes avail- able. Therefore, we will be monitoring patterns of choice during January -June I987. T}! 3_2 Housestaff Attitudes Towards The Acquired Inmunodeficiency Syndrome. MOLLY CO0KE‘, B. KOENIG, *University of California, San Francisco, San Francisco, CA. Care of AIDS patients elicits strong emotional and psychological responses in providers. In September 1983, we surveyed medical houseofflcers (H0) at UCSF, addressing estimation of risk to health care workers (HCN's), anxiety elicited in Ho's and satisfaction in the care of AIDS patients. 68% of res- pondents felt HCN's were at risk of acquiring AIDS. Men and women HO's differed significantly in their estimation of risk: 84% of men versus 48% of women agreed HCN's were at risk (p=0.004). Sense of risk affected precautions followed with significantly more men reporting mask use and glove wearing. >80% of medical housestaff were at least mildly anxious about taking care of AIDS patients and estimated that 20% were ”very anxious". 97% reported worry- ing about getting AIDS at least on occasion. 35% reported worrying about giv- ing AIDS to a famlly member, 20% reported dreams or nightmares about AIDS and 18% reported symptoms which they felt were suspicious of AIDS. Men were more likely to report their preoccupation, dreams and nightmares and rated their anxiety significantly higher than did the women respondents (p=0.03). House- staff chose the midpoint of a 4 point Likert scale when asked to express satis- faction. Increased contact with AIDS patients predicted a less negative res- ponse with 68% of HO's who had cared for <10 patients disliking AIDS care com- pared to 35% who had cared for >10 (p=0.02). To a large extent these responses are gender dependent. Ho's have responded to this lethal epidemic with exper- tise and compassion but need more assistance in handling the stress induced by assuming their professional responsibility. TH.3.3 Concerns of Medical and Pediatric House Officers about Acquiring AIDS from their Patients R. NATHAN LINK'. ANAT R. FEINGOLD". MITCHELL H. CHARAP‘. KATHY FREEMAN“. STEVEN SHELOV*‘*. ‘New York University School of Medicine, "Monteflore Medical Center "‘Albert Einstein College of Medicine; New York, NY. USA To assess the degree of house officers‘ concerns about acquiring AIDS from their patients. we surveyed medical and pediatric residents in four New York residency programs with large AIDS patient populations. During the study period. 2/1/86— 5/1/86. multiple choice questionnaires were distributed to all house officers present at the study sites (outpatient clinics) and were completed anonymously. or 263 questionnaires distributed. 258 (98%) were returned. Thirty-six percent of medical and 17% of pediatric house officers reported needlestlck exposures to blood of AIDS patients. Forty—eight percent of medical and 30% of pediatric house officers reported a moderate to major concern about acquiring AIDS from their patients Thirty percent of all respondents believed concern about AIDS increased the stress of their residency moderately to extremely Multivariate analysis demonstrated that a greater concern about personal risk was independently associated with an increased number of AIDS patients treated (p-ODIL the year of residency training (greater concern in earlier years. p-QOOZh and the type of residency program (greater concern in medical than pediatric house officers p=0.0003). A history of needlestick exposure was not significantly associated with increased concern (p=OA). Thirty percent of all respondents indicated they would want to know their current HIV serology status. Ninety—three percent of respondents believed concern about acquiring AIDS did not adversely affect their care of patients; however, 25: stated that they would not continue to care for AIDS patients if given a choice. The results demonstrate a considerable degree of concern about acquiring AIDS among house officers caring for AIDS patients and suggest the need for housestaff training programs to formally address these concerns THURSDAY, JUNE 4 Tl1_3.4 AIDS Train the Trainer Program for Health Care Providers: California Nurses Association's Innovative Approach HELEN SCHIETINGER*, Z.A. FITZHUGH*, P.K. MCCARTHY*, C. MORRISON**, *California Nurses Association, San Francisco, CA, **AIDS Health Services Project, San Francisco, CA. Many health care providers still harbor fears and misunderstandings about AIDS that negatively affect the delivery of patient care. In order to resolve these fears and misunderstandings, the California Nurses Association, working with the AIDS Project Los Angeles and the San Francisco AIDS Foundation, devel- oped, implemented, and evaluated an innovative AIDS "train the trainer" pro— gram. The program was designed to replace didactic lectures with more effective methods to meet the needs of adult learners. By April 1987, 27 two—day train- ings were conducted throughout California to certify 750 key health care pro- viders in both adult learning principles and AIDS content. Creative teaching strategies such as guided fantasy, role play, and simulation were utilized to encourage group interaction and the analysis of sensitive issues underlying the fear of AIDS. By May 1, the 750 certified AIDS educators had each conducted instructional programs for groups of 25 or more health care providers, includ- ing direct care providers, support services personnel, and administrators. A total of 18,750 people were educated in these secondary trainings. Summative evaluation of the primary trainings indicates that this model is effective for increasing trainers' competence and confidence related to teaching about AIDS and HIV infection. Summative evaluation of the secondary trainings is still in process. TI1.3.5 Low Occupational Risk of HIV Infection for Dental Professionals (DP). ROBERT S. KLEIN*, J PHELAN*, GH FRIEDLAND*, K FREEMAN*, C SCHABLE**, N STEIGBIGEL*, ET. AL. *Montefiore Medical Center, Albert Einstein College of Medicine, Bronx, NY, and **Centers for Disease Control, Atlanta, GA, USA. In Oct. 1985 we began a study of the prevalence of serum antibodies (Abs) to HIV in DP recruited via a mailing and at professional meetings. Subjects com- pleted questionnaires on demographics, type, duration and location of practice, AIDS high risk behavior, precautions used in treating patients (pts), and types of pts treated. HIV Abs were assayed by BIA, with Western blot confirmation of positives. Homosexual men and parenteral drug abusers were excluded. Of 1009 subjects. 919(912) were dentists, 90 hygienists; 807(802) were male. Major types of dental practice were restorative(521) and oral surgery(SZ). 324 DPs(3ZZ) practiced in the New York City area, 43(42) in Miami, and 20(22) in Houston, Los Angeles, or San Francisco. 116/988 respondents(122) had treated known AIDS pts (median 2,range l—78), 708/983(7ZZ) members of AIDS risk groups. At time of screening 313/977(321) used gloves at all times, 579(592) for selec- ted pts or procedures, 85(92) never. Eye protection was used by Sal/899(6SZ) always, 238(272) sometimes, 80(91) never. 53l/936(57Z) had increased use of precautions since 1983, 831 at least partly due to concerns about AIDS. 895/987 (91%) reported accidental parenteral puncture wounds by instruments; median number per subject over the preceeding 5 years was 10(range l-1000). 568/1002 respondents (571) had not received hepatitis B vaccine; of these, 122/546 tested (22%) had Abs to hepatitis B surface antigen. None of the 1009 subjects had Abs to HIV confirmed by Western blot. Therefore, DP appear to be at very low risk of occupational acquisition of HIV infection (951 0.1., 0 to .003), even though recommended precautions are not always used and accidental parenteral puncture wounds are frequent. Routine use of recommended precautions should make any risk even more remote. TI! 3 6 Prevalence of Unsuspected Human Immunodeficiency Virus In Critically ' Ill Emergency Patients JAMES L. BAKER*, G. Kelen*, R. Sivertson*, T. Quinn**, *Department of Emergen- cy Medicine, The Johns Hopkins Hospital, Baltimore, MD, **Laboratory of Immun— oregulation, National Institute of Allergy and Infectious Disease, Bethesda,MD Implementation of recommended guidelines for prevention of transmission of the human immunodeficiency virus (HIV) to health care workers is not uniform, and in part is based on a lack of recognition of the extent of asymptomatic HIV infection in this country. In order to reinforce the need for appropriate infectious disease precautions, we tested for HIV antibody seropositivity in 203 critically ill patients presenting to an urban emergency department, none of whom had a previous diagnosis of HIV infection. We found that 6 (3%) of the total were seropositive by both enzyme—linked immunoassay (ELISA) and Western Blot, and that these 6 represented 16% of the 37 patients between 25 and 34 years of age. All seropositive patients were victims of trauma, and of 10 gunshot wound victims between the ages of 25 and 34, 3 (30%) were seropositive. None of the seropositive patients had been suspected of being infected, all were actively bleeding, and all required multiple invasive procedures, includ— ing by paramedics in the field and by physician staff in the emergency depart- ment. These results reinforce the necessity of infection control precautions, whe— ther or not previous suspicion of HIV infection exists. 155 Clinical Studies—Opportlmistic Infections TH.4.1 Preliminary Results of a Phase [-11 Trial of Trimetrexate Therapy for Pneumocystia Pneumonia in AIDS Patients CARMEN J. ALLEGRA*, CHABNER*, C. TUAZON**, H. C. LANE*, D. ARAKAKI*, H. MASUR*, et al., *National Institutes of Health, Bethesda, MD, **George Washington University, Washington, D.C. Trimetrexate (TMTX), a potent inhibitor of dihydrofolate reductase, has been shown in laboratory studies to have potential B. advantage over conventional agents for therapy of Pneumocystis carinii pneumonia (PCP). In this trial, AIDS patients with histologically proven PCP (first or subsequent episode) were treated 00 x21 days) plus leucovorin (LVN) 31th TMTX (30 mg/M (20 mg/M Qfih x 23 days) * Sulfadiaziue (S) (1.0 g 06h x 21 days). Pharmacokinetics of TMTX were highly predictable with a t 1/2 of 9 hours. Toxicity possibly related to TMTX was minimal, consisting of purpuric rash (1/42 patients), mild granulocytopenia (5/42 patients) and thrombocytopenia (8/42 patients), plus mild transaminasemia (8/42 patients). Cytopenias were easily managed by dose adjustments of TMTX or LVN. Complete responses were seen in 9/13 previously untreated patients who received S + TMTX/LVN; 9/14 previously untreated patients who received TMTX/LVN without S; 9/13 patients who failed conventional therapy and received TMTX/LVN without 5. Relapses within 1 month were seen in 5 patients. Results of this trial indicate that TMTX i S is an effective and well tolerated therapy for PCP, the relative merits of which need to be compared to conventional agents in a larger controlled trial. TI1.4.2 Studies on Successful Eflornithine Treatment of Pneumocystis Carinii Pneumonia (PCP) in AIDS Patients Failing Conventional Therapy B.D.Mclees, J.L.R.Barlow, R.J.Kuzma, D.C.Beringtang, P.J.Schechter, A.Sjoerdsma, Merrell Dow Research Institute, Cincinnati, Ohio. Eflornithine (E; DL-d—difluoromethylornithine) is an irreversible inhibitor of ornithine decarboxylase with activity against several protozoan species re- lated to Pneumocystis carinii (PC). This antiprotozoan activity, plus dramatic therapeutic results in a few patients, led to compassionate E use by 189 inves— tigators treating 345 AIDS patients with proven PCP. The patients, entered be— cause of treatment failure and/or intolerance to trimethoprim-sulfamethoxazole (TMP-SMX) and/or pentamidine (P), had no therapeutic alternatives and little or no chance for survival. The recommended E dose was 100 mg/kg I.V. q6h for 14 days followed by 4-6 weeks oral therapy at 75 mg/kg q6h. Efficacy was measured by survival to hospital discharge and clinical response evaluated from changes in arterial blood gases, chest X-ray, defervescence and followup lung biopsy. Survival for patients receiving )4 days of E therapy (266/345) was 10/101 (10%) in patients receiving mechanical ventilation (MV) at study entry and 109/165 (662) for spontaneously breathing (SB) patients at study entry. Survival for subjects receiving >14 days E treatment (160/345) was 10/43 (231) for MV patients and 91/ll7_(781) for 55 patients. Clinical responses were higher: 27/43 (63%) MV patients completing >14 days therapy and 102/117 (872) SB patients had positive responses. Followup examinations showed clearing of PC in 30/74 (40%) patients; the relationship between the disappearance of the cysts and survival was significant (p (.05). E was generally well tolerated with thrombocytopenia (482), diarrhea (20%) and leukopenis (161) reported as the most frequent adverse events. The survival, clinical response and clearing of PC in patients with little/no expected survival demonstrate E effectiveness comparable to first line treatment with TMP/SKX and P. T|1_4.3 Cyclosporin A may induce deterioration in patients with AIDS. ANNE PHILLIPS*, M. FANNING, P. HALLORAN, R. COATES, M. KLEIN, S. READ, et al., University of Toronto, Toronto, Canada MSG 2C4. The pathogenesis of AIDS remains unclear but it may be in part an immune-cyto— penia. The lack of efficacy of other therapies and the proven benefit of Cyclosporin A (CyA) for many patients with immune cytopenias as well as favour— able reports from French investigators prompted this study in the belief that CyA might ameliorate some of the immunoregulatory disturbances involved in AIDS. Eight stable AIDS patients were treated for a mean duration of 49 days with biologically active doses of CyA. Clinical, hematologic, immunologic, renal and hepatic functions were followed at least weekly before, during and after administering CyA. The white count, lymphocyte count, hemoglobin, platelet count, total T cells, T4 and T8 cells fell significantly during treatment. HIV—l was cultured more frequently during treatment. The white blood count, platelet count, total T cells and T8 cells reached pre-treatment values after therapy was withdrawn. Hemoglobin remained significantly lower than prior to treatment and T4 cells rose towards pre—treatment values but did not reach statistically significant levels. Severe toxic symptoms, not characteristic of CyA therapy in other patients, affecting functional capacity were experienced by all 8 patients and necessit- ated discontinuation of the drug in 6. The symptoms included nausea, vomiting, anorexia, fatigue, pain and extreme swelling and increased number and size of Kaposi's lesions. CyA does not improve, and may worsen the symptoms and laboratory findings in AIDS. THURSDAY, JUNE 4 TH'4 4 Cytomegalovirus and Adenovirus Infections: Response to DHPG. 'A.S. 'I'YMS, 'D.L. TAYLOR, ‘J.M. DAVIS, "D. TAYLOR—ROBINSON, "'A.J. PINGiING, ‘D. . JEFFRIES, et al ‘Virology Department, “'Immunology Department, St Mary's Hospital Medical School, London W2, "Clinical Research Centre, Harrow, UK. Infections with human cytomegalovirus (CMV) show marked sensitivity to treatment with DI-IPG in vitro and this drug has proven clinical efficacy against disease in AIDS patients. We now have evidence that infections with adenoviruses also respond to treatment with DHPG, which maybe important in the clinical management of opportunist infections in AIDS patients. Patients suffering pneumonitis, retinitis or colitis were treated with DHPG on the basis of virological, histological or clinical evidence that CW was the aetiological agent. During these investigations, repeated isolations of and/or adenovirus was made and viruses were characterized by restriction analysis of viral DNA after comparison with prototbipe strains. Plaque- reduction assay showed the sensitivity of adenovirus isolates (EDSO 7 to ’10 5114) to DI-IPG was about 10—fold lower than values recorded for CMV, but within the range of concentrations achieved during treatment (peak levels 46 — 56 pm 15 minutes post—infusion 500 mg/kg bd). Sensitivity of adenovirus isolates in cell culture was confirmed by studies using high multiplicity of infections. The clinical, virological and molecular aspects of the study will be illustrated by comparison of three AIDS patients all treated with DHPG from whom 1) only CMV, 2) only adenoviruses, 3) both viruses were isolated. CMV T" 4 5 Successful Therapy of Cytomegalovirus (CMV) Infections in Patients ' ' (pts) with Acquired Immunodeficiency Syndrome (AIDS) with Gan— ciclovir (DI-IPG) DOUGLAS T. DIETERICH, F. LAFLEUR, A. CHACHOUA, C. WORRELL, Kaplan Cancer Center, New York University Medical Center, New York, NY since January 1985, 122 pts with AIDS and severe CMV infection were treated with DI-IPG. 118 were male, 4 were female. 117 males were homosexual, 1 male and 1 female had transfusion related AIDS, 3 females were sex partners of IV drug users. The mean age was 38 years. 25 had Kaposi's sarcoma, 70 had PCP and 36 had both. Diagnosis of CMV was made on positive tissue biopsy, a positive urine culture or positive fundoscopic exam. Responses were measured clinically and virologically by objective criteria including endoscopy. Sites of CMV were: colon and rectum 51 (42%), retina and CNS 46 (38%), esophagus, stomach and small bowel 14 (11.5%), lung 9 (7%) and liver 2 (1.5%). DHPG was administered at a dose of 5 mg/kg IV BID for 14 days. On relapse pts were retreated and placed on maintenance (M) of 6 mg/kg daily. Clinically, 88 of the 122 improved (72%), 8 stabilized (6.5%) and 22 worsened (18%), 4 were not evaluable (3.2%). 107 pts survived for more than 4 weeks. overall median probability of survival was 19 weeks with a median follow up of 16.6 weeks. 59 (48%) pts became culture negative, 16 (13%) did not change. 47 (39%) were not evaluable. Revers- ible leukopenia < 2,000 occurred in 6/122 and skin rashes in 4/122. 62 pts received M with DHPG. Probability of survival of pts on M was 33 wks compared to 18 wks on no M p < 0.001. In PCP pts, probability of survival from date of PCP was 45 wks on M, compared to 35 wks for pts not on M p < 0.001 (controlled for PCP prophylaxis). We conclude that Ganciclovir (DI-IPG) is effective in the treatnent of CMV in AIDS pts. A high proportion of pts will relapse, M treat- ment may be associated with an increased probability of survival. TH.4.6 A Clinical Trial of Recombinant Alpha Interferon in Patients with AIDS G.H. FRIEDLANDI, S.l-I. LANDESMANZ, c.s. CRUMPACKER3, M... H1Rscn4, I-I.H. HANDSFIELD5, D.J. PIZZUTIG, et. a1. 1Montefiore Medical Center, Bronx, NY, ZSUNY Health Science Center, Brooklyné NY, éBeth Israel Hospital, Boston, MA, 4Massachusetts General Hospital, Boston, MA, Harborview Medical Center, Seattle, WA, 6Hoffmann La—Roche, Clinical Research and Development, Nutley, NJ. We report the results of a randomized, double—blind, placebo-controlled trial of recombinant interferon—alpha—ZA (Roferon®—A) in unselected AIDS patients without Kaposi's sarcoma. Sixty—seven patients were enrolled and received I of 3 regimens: placebo or 8 or 36 million units of Roferon®~A 3 times weekly IM for 12 weeks. The 3 groups were comparable in number of patients, age, gender, risk behavior, clinical measures of HIV infection, and initial T4/T8 ratios. Thirteen patients received less than 4 weeks of therapy, 54 patients were thereby available for efficacy analysis. There were no significant differences in survival or rate of opportunistic infection during or after treatment in the 3 groups. A significant decrease in T8 cells occurred in the 3 million unit group but no significant differences in T4, total lymphocytes or T4/T8 ratio occurred. There were no significant differences in adverse drug reactions including those in central nervous and GI systems, or laboratory findings among the 3 groups. Six patients required reduction in dose because of side effects, 4 in the 3 million and 2 in the 36 million group. Seven patients dropped out due to adverse reactions, 2 in the 3 million group, 4 in the 36 million group, and l in the placebo. The preliminary analysis of this study did not demonstrate effectiveness of Roferon®—A in the treatment of unselected AIDS patients without Kaposi's sarcoma. However, the drug was acceptably tolerated and might have a role in therapy of AIDS patients in combination with other agents. 156 Prevention/Public Health—Drug Users and Other High Risk Groups High Rate of Hl‘Lv-III/HIV Exposure in IVDA's fmn a Small-Si zed City and the THH51 Failure of Specialized Methadone Maintenance to Prevent Further Drug Use RICHARD G. MARLINK", B. FOSS", R. SNIFT***, W. DAVIS“, M. ESSEX****, J. GROOPMAM, et a ., *New ng an Deaconess Hospital, Boston, MA, “New Redford Center for Hunan Services, New Bedford, M, ***Brown University, Providence. RI, ****Harvard School of Public Health, Boston, MA. To investigate the seroprevalence to HTLV-III/HIV and HTLV-I in a non-metropolitan area in New England, we conducted a voluntary screening program in New Bedford, MA, from April 1986 to December 1986 at the only drug treatment center serving this pre- dominantly Caucasian caununity of 100,000. 01‘ greater than 300 clients, 114 chose to be screened in our program. 27 clients (211%) were found to be seroposltive for HTLV-III/HIV and none were found to be seropositive for HTLV-I. All seropositive clients were given individual, long-term counseling and medical follow-up in addition to the opportunity to receive "methadone maintenance", instead of simply short-ten“ drug detoxification with methadone. Positions in the otherwise full methadone maintenance program were still offered to all seropos‘itive clients. Even with additional counseling, medical care. and priority for entrance and continuation on methadone maintenance, 67% (18/27) returned to I.V. drug use as determined by urine drug screens, personal histories and drop-out rates in the 6 months since initiating this specialized methadone maintenance program This is canpared to 7% (10/134) for the entire established methadone maintenance program over the sane period, and to 24% (6/25) for a group of seronegative clients, and to 8% (2/25) for a group of "never tested" clients who were matched by age, sex, employment status, and drug usage at the beginning of the 6 month folow-up of the seropositive cohort. The high rate of seropositivity to HTLV-III/HIV in this smaller sized cannunity and the lack of compliance to a novel attempt at curbing continued I.V. drug use among seropositivies makes the call for new programs geared to prevention of viral trans- mission in this population all the more urgent and difficult. TH5 2 A Coupon Program: AIDS Educatim and Drug Treats-mt ' m JAM, L. ROI‘KIEWICZ, N.J. State Dept. of Health (NJSDH), East Orange, NJ. In New Jersey, IV addij ocmprise the majority of AIDS cases, but under 10% are currently enrolled in a drug treatment modality. Impositim of patient fees in 1981 resulted in a loss particularly of black males. This paperdescribesaneffortbyttleNJSDI-lbegiminginsegtarberwBGto ufluoeaddictsmmtreahrentamitoprmddeAIDSeducatimooredmetm rate of HIV transnissicn. Serially mnbered ooupms, redeemable for a free outpatient detoxification, were distributed in inner-city neighborhoods by previously established ex-addict AIDS outmach workers. Eligible recipients were Iv dnigsmsersvdnhadmtstmghtueammtinat leastaieyear. Programs were reimbursed under omtract for collecting derograflxic data on coupon bearers, providing hernin detoxificatim and priority for extended treatment, providing one hour of AIDS education with pre- and post—testing, and maintaining a file matching ooupcn mnbexs with patient name. By January 15, 1987, of 607 ompcns distributed, 76% had already been redeemed. Cbupcn zedeareczs were 76% black and 81% male. Fifty-four peroaithadagesbetwemZGaIflSSandMWereoverafa; 41%hadno previous treatment attetpts and 44% had 1-3 attanpts. AIDS emcation had beenpzovidedandpm—andpost—testsadninisteredtooverMof redeaners. The program appears successful in meeting its goals. T'1.5 3 Evidence of Reduced AIDS—associated Risk Behavior in ' Homosexual/Bisexual Hen but Not in Heterosexual: or IV Drug Users in A Widely Dispersed 0.5. Counties. MIRIAM J. ALTER , D. FRANCIS and the CDC Senginel County study group Centers for Disease Control, Atlanta, GA and Berkeley, CA Since hepatitis B virus and human immunodeficiency virus have remarkably similar transfusion patterns, epidemiologic changes in one should mirror epidemiologic changes in the other. We have used changing epidemiologic patterns of hepatitis B in A U.S. counties, 1 each in Florida, Alabama, Colorado and Washington as an indicator of the effectiveness of AIDS prevention measures (presumably individual behavior changes). In these k counties there was, for the first time, a dramatic change in hepatitis B cases associated with homosexual behavior (20! of all cases in 1985 versus 91 in 1986). In contrast there was I relative and absolute increase in the number of IV drug-related cases (161 vs. 271) and documented heterosexual— intercourse-related cases (121 vs. 161). Racially there was little change (approximately 2/3 white and 1/4 black) but there was a 101 increase in female cases (331 in 1965, #31 in 1986). From these data it can be inferred that the AIDS-prevention message has been heard and acted upon by a considerable number of homosexually active men across the United States, but similar behavior change is not yet apparent among either heterosexual men and women or IV drug users. THURSDAY, JUNE 4 T}! 5 4 Use of Condoms for the Control of AIDS: A Cross-Section Study in ' ' Rikai District, Uganda. A.M.T. LWEGABA, Project Mgr., Uganda AIDS Programme, Kampala. AIDS, locally known as ”SLIM” has been known in Uganda since late 1982, and then described as an obscure wasting disease. It was not until late 1984 that the disease became associated with AIDS, as proven by serologic tests. The areas most greatly affected are Rakai and Masaka Districts. The incidence rate in Rakai was 0.12% in 1986. Amongst preventive measures instituted was the distribution of condoms primed by a health education campaign. By August 1985, 20,000 were distributed. Recommendations of the Regional Conference on AIDS inAfrica (Brazzaville: November 1986) include studies of attitudes on condom usage and methods to increase availability, distribution and use of condoms. A study has been initiated in the Rakai District to determine attitudes and use of condums among randomly-selected cohort of sexually-active adults. Market places are good venues for cross-sectional selection in rural Uganda and comprise the study sites. Mature, experienced health professionals administer standardized interview forms and record responses to questions regarding subject's biodata, knowledge and use of condoms, and knowledge and affect on sexual behavior of AIDS. Interview records are serially numbered and names deleted to ensure confidentiality. Data will be analyzed categorically, subjected to significance test, and presented in tables and graphs. T}i_5 5 Effect of an AIDS education program on increasing condom use in a cohort of Nairobi prostitutes ELISABETH N NGUGI, FA PLUMMER, DW CAMERON, M BOSIRE, J0 NDINYA—ACHOLA et 31. Kenya Medical Research Institute; Univ Nairobi; Ministry of Health, Nairobi, Kenya; Univ Manitoba, Winnipeg. In order to control sexual transmission of HIV, modification of sexual be— haviour through education must be achieved. We have been studying cohort of Nairobi prostitutes for 24 months who are at high risk of HIV infection (over 80 Z positive) and pose a substantial risk to their clients. Beginning in November 1985 we provided education on AIDS to this cohort of 596 women. Several different methods of education — public meetings, individual counsel— ling on the basis of HIV results and general health education — were employed. In June 1986 distribution of condoms through the clinic began. In October 1986 we began surveying the frequency of condom use in the cohort. 126 women who were newly recruited served as controls. Some condom use was reported by 8 Z of women prior to the education program vs. 90 Z of the most intensively educated group (Grp I), 85 Z of the less intensively educated group (Grp II) and 73 Z of the control gropu (Grp III). In Crp I and II no condom use was reported by 5/61 women who received counselling vs 10/33 women who did not receive counselling (p4:.05). HIV antibody status did not influence frequen— cy of condom use. Condom use was more frequently client initiated in the control group. We have witnessed a remarkable increase in condom use as a result of the program. Although more intensive education resulted in incre— mental increases in condom use, minimal education with provision of condoms was the most important step. “ts-6 Drug Use and Sexual Behavior Change in a Cohort of Homosexual Men DAVID G. OSI‘W, M. VAN RADEN, L. KINGSLEY, R. FOX, J. WDLEY, R.A. KASIUN, and the Multicenter AIDS Cohort Study (MACS) . We have examined the association between the use of recreational drugs (marijuana, cocaine, volatile nitrites, anphetamines, sedatives, hallucinogens and opiates) and sexual behavior in a cohort of 5,000 hunosexual/bisexual nen residing in Chicago, Balthmxe/Washington, D.C., Los Angeles and Pittsburgh. At both baseline and six nonth follow-up evaluations, nen using recreational drugs were significantly more likely to be engaging in sexual practices be— lieved capable of transmitting HIV infection. These associations were strongest when drug use with sexual activity was exanined and were independent of the nunber of sexual partners. Forthermore, when changes in sexual behavior were examined, nen who had been using recreational drugs were significantly less likely to have reduced their level of unsafe sexual behavior than nen not using drugs (relative risks ranging fran 1.2 to 2.2 for each drug exanined). These findings provide a possible explanation for the observation of a higher prevalence of HIV antibody positivity in MACS participants using recreational drugs and suggest intervention strategies for controlling the sexual spread of HIV infection. 157 Roundtable Discussion ms Panel Organized By: Developing Community Based Service Organizations Paul Kawata National AIDS Network Washington, DC. Tim Holfred, San Francisco AIDS Foundation, San Francisco, California Richard Dunne, Gay Men's Health Crisis, New York, New York Judith Peabody, Gay Men's Health Crisis, New York, New York Epidemiology—Perinatal Transmission and Tl1.7.1 National Trends in Perinatally Acquired AIDS, United States. MARGARET J. 0XTOBY*, M.ROGERS*, P.THOMAS**, S.MANOFF*, K.WINTER*, R.BYERS*, *Centers for Disease Control, Atlanta, GA; **NYC Dept of Health, NY As of January 19, 1987, A23 children under 13 years of age with AIDS have been reported to CDC; the number of cases is currently doubling every 13 months. Perinatally acquired cases (PA) continue to predominate, accounting for 338 (80%) of cases; 24 (6%) are nemophiliacs, 50 (12%) are children infected through transfused blood, and 11 (3%) have incomplete risk histories; no case acquired through household, school or daycare contact has been reported. Notably, the geographic distribution of children with PA is changing. The proportion of cases outside the high-risk areas of New York, New Jersey and Florida has increased from 21% of cases diagnosed through 1984‘to 37% of cases diagnosed in 1985-1986 (p=0.002). This trend is consistent with the trend among women with AIDS, which shows an increase from 23% to 32% in cases reported outside these high-risk areas. The risk factors of mothers of children with PA are also changing; the proportion of mothers infected through hetero- sexual contact has increased from 342 of PA cases diagnosed through 1984 to 44% of cases diagnosed in 1985-1986 (p=0.01); nearly all other mothers are IV drug abusers. PA continues to affect mostly blacks (642 of cases) and Hispanics (252), with cumulative incidences in these respective populations 29 and 18 times the rate among whites. Although older children with AIDS are being increasingly recognized, the median age at diagnosis has remained con- stant at 6 months, reflecting increasing seroprevalence rates in childbearing women. Compared to children older than 1 year of age when diagnosed, children diagnosed under 1 year of age are more likely to have Pneumocystls carinii pneumonia as an initial opportunistic infection (71% vs 36%), and have a poorer prognosis (median survival time after diagnosis of 4 months vs 22 months). T}! 7 2 Perinatal Transmision of HIV in Intravenous Drug Abusers (IVDAs) ' ' PETER A SELWYN*, EE SCHOENBAUM*, AR FEINGOLD*, M MAYERS*, K DAVENNY* M ROGERS** et al., Montefiore Med. Ctr.,/Albert Einstein College of Medicine, Bronx, NY, **CDC, Atlanta, GA, USA. To determine the rate and outcome of perinatal transmission of HIV to infants we are prospectively studying pregnant IVDAs and their offspring. Women in aNYC methadone program (MMTP) receive prenatal care and HIV serum antibody (Ab) test- ing. Infants are examined at birth and at 3 month intervals, and monitored for growth and development and signs of illness. Cord and peripheral blood are test- ed serially for HIV Ab and cells stored for HIV culture. Since 9/85, we have studied 16 infants of 15 seropositive (SP) mothers and 30 infants of 29 seronegatives (SN). Mothers did not differ by age or obstetrical complications. 14/15 (931) SPs were non—white vs. 18/29 (622) SN5 (P<.05). In— fants did not differ in frequency of intrapartum fetal distress, APGARs, gesta- tional age, or neonatal complications. Mean birthweight was 2860g for SP3, 28303 for SNs. 0f 12 infants of SP mothers tested, all had HIV Ab in cord or neonatal specimens; none of 17 infants of SNs had HIV Ab at birth or thereafter.No in- fant has AIDS to date. One SN died from sudden infant death syndrome. 12 in- fants of SP mothers had HIV Ab tests Z4 weeks of age (mean of 27 wks.at last follow-up); 6 remain SP (502), 6 became SN (50%). Those becoming SN had mean age at first negative Ab test of 31; wks. (range 12- 55). 1/6 infants SP at last test was healthy, 5 had either: failure-to-thrive (FTT)(3), developmental delay(3), lymphad- enopathy in > 2 sites (LA) (3) , persistent oral thrush(1) , or multiple bacterial in- fections(BIs) . 5/6 infants becoming SN were well; 1 had FTT, LA and Bis. 2/17 infants of SNmothers (mean age 30 wks.) had LA(1) or 315(1). Results show that maternal HIV Ab was not associated with adverse peri-or neo- natal infant outcome. Preliminary data showed that 6/12 (501) of infants of SP mothers became SN within 1 year; 5/6 of these infants remained healthy. The rate of HIV transmissionmay be 9 years. Mathematical modeling had estimated the mean incubation period for adults will be 5 years, but current data suggest it will be longer. Because of the long incubation period, the incidence of TA—AIDS continues to increase in all age groups. No TA-AIDS cases have been reported in recipients of blood screened for HIV antibody whereas 10 TA—AIDS patients reported receiving their transfusions in the first 4 months of 1985. We estimate that 10,000 persons in the United States have TA HIV infections. Our study of families of adults with TA—AIDS found 38% had steady sexual partners, and transmission had occurred to 16% of the females and 8% of the males. If these estimates are generalized to all infected persons, 3,800 infected persons may be involved in sexual relationships, and 450 may have already transmitted infection. For 10 reported AIDS patients, the only risk for infection appears to be perinatal or sexual contact with an infected transfusion recipient. Secondary transmission from previously infected recipients may now be occurring more often than transmission by transfusion. Til-10.2 The Transfusion Safety Study JAMES W. MOSLEY*, THE TRANSFUSION SAFETY STUDY GROUP* **, *USC School of Medicine, Los Angeles, CA, **other participating institutions. The Transfusion Safety Study (T85) is a multifaceted, cooperative evaluation of factors influencing risk of transfusion-transmitted HIV infection, and in- teractions associated with progression. Subject groups include: (1) Persons in the 4 highest prevalence areas of the United States who donated blood in Sep— tember, 1984, through January, 1985, just prior to routine donor screening; (2) recipients of components from anti-HIV(+) and (-) donors; (3) patients with congenital clotting disorders (CCD) receiving concentrates and components; (4) patients with congenital anemias (CA) receiving large numbers of transfusions; (5) untransfused subjects with CCD or CA; and (6) household contacts of treat— ed subjects having CCD or CA. Findings to date include: (1) The estimated prevalence of anti-HIV positiv- ity among donors was 10 to 20 per 10,000 at the time of the survey; (2) homo— sexual contact was overwhelmingly the most important risk factor among donors; (3) 892 of recipients of anti-HIV(+) components have become anti-HIV(+); (4) there is a large difference in anti-HIV positivity associated with Factor VIII and Factor IX concentrates (78 vs 441); (5) only ZOZ of CCD subjects treated just with components are anti-HIV(+); (6) only 62 of heavily transfused CA sub- jects are snti-HIV(+), and these cases are confined to high prevalence areas; (7) 171 and OZ of sexual and non—sexual household contacts of anti-HIV(+) CCD and CA have become seropositive; (8) no seroconversion of any subject has been observed on follow-up. (Supported by Contracts No. N01—HB-4-7002 and Nol-HB- 4-7003 of the National Heart, Lung, and Blood Institute.) THURSDAY, JUNE 4 TH.10.3 Clinical Observations on HIV Seropositive Hemophiliacs after 4 1/2 Years of Followup and Efficacy of Heat—treated Products. MARION L KOERPER, J.A. LEVY, University of California San Francisco, San Francisco, CA. Individuals with hemophilia represent one of the four major groups at risk for developing acquired immunodeficiency syndrome (AIDS) because of their use of blood products. The majority of hemophiliacs seroconverted to human immunodeficiency virus (HIV) by late 1982. We have been prospectively following a group of 84 hemophiliacs since July 1982. All were healthy and asymptomatic at that time. Our results show the following: HIV Positive HIV NggLative Factor Total Asymptomatic AIDS ARC Total VIII 45 36 4 S 14 IX 10 9 0 l 15 0f the iactor VIII patients, 112 have developed AIDS and died during the past 4 1/2 years, and 9% have developed ARC. 0f the factor IX patients, 107. have developed AIDS and died; none have symptoms of ARC. In 1984, all of the seronegative patients were switched to factor VIII and IX concentrates that had been heated at 60 or 68° for 72—77 hours, and all have remained seronegative and asymptomatic for 2 1/2 years. These patients have received 1000 — 100,000 units of the concentrates. These results indicate that in 4 1/2 years 112 of seropositive hemophiliac patients have developed AIDS and 726 ARC. These results also document the efficacy of heat—treatment at 60 or 68 for 72—77 hours in eliminating HIV from factor VIII and IX concentrates. T|1,10_4 No Anti-HIV Seroconversion after Replacement Therapy with Pasteur- ized F VIII Concentrate. A Study of 151 Patients with Hemophilia A or von Hillebrand's Disease. ' KLAUS SCHIMPF*, H.H. BRACKMANN, N. KREUZ, B. KRAUS, F. HASCHKE, N. SCHRAMM et al. *Rehabilitation Hospital and Hemophilia Center Heidelberg, Rehabilitation Foundation, Federal Republic of Germany Transmission of hepatitis viruses and HIV has proven to be a risk of repla- cement therapy in hemophilia. As regards F VIII products a concentrate (Hemate HS or P) in which viruses are inactivated by heat-treatment over 10 hours at 60° C in aqueous solution is available since 1979. Our clinical studies have shown that this product does not transmit HBV and HNANBV. As the product was manufactured by 80% from US plasma it was necessary to prove that it also does not transmit HIV. As it is, for ethical reasons, not possible to treat a con- trol group with non-virus-inactivated F VIII, non-transmission of HIV can only be proven if anti-HIV seroconversion does not occur in larger groups of pa- tients treated exclusively with this virus-inactivated product. We collected data from 151 patients treated with Hemate HS (P) who had never before re— ceived blood or blood products. Therapy was started between Feb. 1979 and Jan. 1986 (median July 7, 1983). The median length of observation till the last anti-HIV testing was 24 (3 - 83) months, the median total dosage was 17,000 (500 - 2,155,375) IU of F VIII, the median patient age was 6 (0.5 - 68) years. In none of these patients anti-HIV seroconversion (ELISA test) was observed. According to the rule of three, the upper 95% confidence limit for a random sample of 60 cases with zero events would be 3/60 or 5%. For greater numbers of n cases. as in our study. the range of confidence narrows increasingly. The period of observation of this study is hitherto the longest. TH..105 Antibodies to HIV in Israeli Hemophiliacs: Prognostic Significance of Serological Profile SHLOMIT 0RGAD*, G. MALONE“, R. ZAIZOV***, U. MARTINIWITP‘, E. GAZIT*, M. X , S eba Medical Center, ISRAEL, “Harvard School of Public Health, Boston, MA, ***Beilinson Medical Center, ISRAEL. We studied 66 Israeli hemophiliacs for antibodies to HIV on blood samples collected between 1978 to 1985. By May 1985, 2 had AIDS, 2 had ARC, 4 had lymphadenopathy, and 58 were asymptomatic. Antibodies to HIV were detected in 40 (60.6%) patients. Presence of HIV antibodies was significantly associated with receipt of non-heat-treated conmercial factor VIII concentrates (NHT.Fac.VIII) between 1980 to 1983. 84.44% of patients treated with NHT.Fac.VIII developed antibodies, compared to 25% treated with cryoprecipi- tates and fresh plasma only. All 40 seropositive patients had antibodies to viral env gene encoded gp120/9p160 antigens. Twenty-four (60.0%) also had antibodle—s to viral 3% gene encoded p24 and/or p55 antigens. While antibodies to gp120/160 persiste during the follow-up time, a loss of antibodies to p24/55 was observed in 25% of seropositive patients from whom multiple samples were available. Gp120/160 positive p24/55 negative hemophiliacs had significantly lower absolute T—helper cell counts and reversed Th,Ts ratios compared to gp120/160, p24/55 seropositive patients. Four of 16 (25.0%) asymptomatic gp120/160 positive p24/55 negative patients developed overt disease within 15 months of the last blood collection. The data suggest that antibodies to gp120/160 are of important diagnostic value while loss of antibodies to p24/p55 may be of prognostic value. 161 TH 10 6 Incidence of liIV—l and HIV—2 antibodies in hemophiliacs ' ' L.G. GURTLER , W. SCHRAMM I. WEIGEL”, J. EBERLE‘ F. . s DEINHARDT ,Max von Pettenkofer Institute, Klinikum Innenstadt, University of Munich, Federal Republic of Germany The presence of antibodies to HIV-l (anti—HIV—l) in a group of hemophiliacs has been monitored since the autumn of 1984. Increasing numbers of HIV-1 infected patients were observed in the years 1981 to 1986 from O to 51% (85 patients of 166 positive for anti-HIV-l). Most infections occured between 1982 and 1984 and only 5 seroconversions were observed since 1985. Only heat or chemically inactivated clotting factor preparation were used for substitution of the patients since the spring of 1985. Two of the five seroconversions in 1985/86 may have been due to a factor VIII preparation inactivated by heat in the dry state and this preparation is no longer used. The other 3 seroconversions possibly were caused by an occasional use of an noninactivated preparation in the beginning of the change to inactivated clotting factor preparations. 38 of the anti—HIV—l positive sera were tested also for the presence of anti—HIV-2 by an ELISA prepared in our own laboratory, immunofluorescence and immunoblot. HIV—2 (LAV—2) for these tests was kindly provided by L. Montagnier. Antibodies specific for HIV—2 antigens were not detected, but crossreactions were observed between anti—HIV—l with HIV—2 antigens particularly epitopes on HIV—2—p27. The data inidicate that the use of adequately inactivated clotting factors can prevent infection of hemophilia patients by this route and that HIV—2 was not' present in the clotting factor preparations used for the substitution of this group of patients. Health Care—Issues in Health Care Delivery TH.11.1 Comprehensive outpatient-based healthcare reduces inpatient stay for persons with AIDS or ARC: the Los Angeles County Model. g§1g§_gggg_figsgpgig§, J.H. LEEbou, M. HEDDERMAN, M. RIPPER, F. SATTLER. Los Angeles County - University of Southern California Medical Center, Los Angeles, CA, USA. Patients with HIV infection have complex health-care needs. Several problems are perceived with hospital inpatient based programs: care for multiple AIDS diagnoses may be dispersed, acute-care services are used for convalescence, procedures require repeated admissions. We have previously reported the cycle of new symptoms, procedure-oriented diagnosis and treatment is more frequent for persons with AIDS than other chronic illnesses and results in an average of 2.3 inpatient admissions/patient/year. As the number of HIV infected persons seeking medical attention increases, alternatives to inpatient care are needed. We examined the effect of an outpatient-based program on the use of acute-care inpatient resources by persons with AIDS or ARC. Each new patient was assigned a physician supervised, primary care nurse and social worker outpatient team (PCT) which coordinated all clinic visits. Physician specialists varied with time based on the patient’s AIDS diagnoses. Over two years of study, a strong inverse correlation was noted between the number of monthly outpatient visits and inpatient length of stay (LOS). Reasons for admissions when regular clinic visits were not planned or available included diagnostic tests, hydration, drug infusions and psychosocial support. Reduction of LOS was associated with significant reduction in charges/patient served. This study supports the hypothesis that an outpatient-based P61“ case- managemmt strategy reduces LOS and charges for persons with AIDS/ARC and may prove to be more flexible in meeting increased demand and patient satisfaction. TH.11.2 Hospital Utilization Patterns and Charges for: the Care of Inner city AIDS Patients: By Risk Group, Sex 6. Race/Ethnicity ERNEST DRUCKER, P. WEBMASTER, A. WEIN, J. BLOOM, ’1‘. DAVIS, M.H. ALDERMAN, et.al., Department of Epidemiology A Social Medicine, Montefioce Medical Center/Albert Einstein College of Medicine, Bronx, NY, USA The hospital records for 39 AIDS patients who received all of their inpatient care at Montefiore between August 198.1 and June 1986, were examined to determine patterns of utilization (length of stay (IDS) and nunber of admissions); charges (room, board and ancillary services); and the relationship of these to patient characteristics. Sixty percent of the patients had a history of intravenous drug abuse (IVDA): 40% were women; 30% were Black: 44% Hispanic; 25% White. Overall, these patients had a mean survival time of 7.75 months after diagnosis (range 3 days to 42 months), and averaged 3.2 admissions (1-18) of 17.6 days (11—186) each. The mean total [.05 was 56.3 days, with total charges $41,484 per patient ($29,143 room A board: $12,341 ancillary services). IVDA's did not differ from non-IVDA's in nunber of admissions, [.05 or charges. Women had fewer hospital admissions (2.4 vs. 3.8): shorter per: patient total we (44.4 vs. 64.7 days): and, accordingly, lower total charges ($33,514 vs. $46,038). These differences (n.s.) were attributable to those 19 patients diagnosed prior to July 1984 when women had a significantly shorter interval between diagnosis and death than men (3.7 vs. 14.2 months, p= .001). Black patients had a shorter total [.05 than Whites and Hispanics (38.3 vs. 66.1 days, 11.3.), and this trend held when stratified for sex and risk group. These findings show total hospital DOS and costs to be considerably higher than a recent comparable lifetime cost study of primarily homosexual patients in San Francisco (Scitovsky, et.al., JAMA, 1986). THURSDAY, JUNE 4 Tli.11.3 Medical Care Costs of Children with El! Infection in Harlem JAMES D. HEGARTY,E. ABRAMS M.D.,V.E. HUTCHINSON M.D.,S.NICHOLAS M.D. M. HEAGARTY M.D., Department of Pediatrics, Harlem Hospital, New York, NY. We have examined the costs of medical care for infants diagnosed with HIV infection at Harlem Hospital (N = 33). From a careful review of patient charts, a total utilization of medical resources was determined and assigned a cost value. The cost value was determined independently from charge-based billing records and standardized to Medicare reimbursement figures whenever possible. The costs of caring for these infants range form $250 to $700 per day. This wide range reflects the variation in resource utilization exhibited by asympto- matic infants (Ab+) versus infants with ARC or AIDS. What is common to all of these infants are lengthy hospital stays as a result of the current absence of viable placement alternatives to the home or hospital Once admitted, these infants may never leave the hospital regardless of medical need. The mean length-of-stay for nine of the unplaced infants was 280 daysand will exceed one year in April 1987. Our study demonstrates that the individual cost of care for several infants has already exceeded $300,000 after more than one year of hospitalization. A recent study reported that the lifetime cost of AIDS in adult patients averages $733 per day over a total hospitalization of 37.6 days fora cumulative mean cost of $25,571. These data for adult patients sharply contrast with our findings for the medical costs accrued by pediatric El! infected patients at Harlem Hospital. The potentiallexpense of caring for these children in our city hospitals is enormous. [ Scitovsky, A. e£.§l. JAMA (vol. 256, no. 22) December 12, 1986.] AIDS Medical Day Care for Intravenous Drug Abusers GUCRIA RGRIGU'EZ, J. JACKSON, N.J. State Department of Health, East Orange, NJ. AIDS Camunity Support unit New Jersey presently ranks fifth nationally in the nunber of confirmed AIDS cases. As of Dec. 1, 1986, this number had risen to 1,709 with an overall mortality rate of 61%. Of special significance is that 52% of the total num- ber of cases are intravenous drug abusers. Presently, chronic long term care facilities and extensive hale health care are not available. Consequently many AIDS/ARC patients mist remain hospitalized at considerable cost. Comprehensive cost-effective specialized services nust be created and made accessible in order to meet the multiple needs of the AIDS/ARC patient. The AIDS/ARC Medical Day Care Program addresses the needs of recipients of the NJ. Medicaid Program who could baiefit from a health service alternative to institutionalization. AIDS Medical Day Care is a program of medically supervised, health related services in an ambulatory structured drug treatment program setting to persons who do not require 24 hours in-patient institutional care and yet, due to their physical and/or mental impairment, need supportive health maintenance and re- storative services. Services provided include medical, nursing, social, trans- portation, personal care, dietary, recreational, rehabilitative, drug counsel- ing and dental. 'Ihe structured drug treatment setting meets their needs, helps reduce transmission, provides a cost effective, humane node of health care and enables IVDA AIDS patients to ranain in the commnity. TH.11.4 TH.11'5 A Hospital—based Volunteer: Program Utilizing Methadone Patients and others to Provide Support for Inner—city AIDS Patients LEA TENNERIELLO, M. CALLAN, L. mkDON, J. LEVINE, B. POUST, E. DRUCKER, Montefiore Medical Center/Albert Einstein College of Medicine, Bronx, NY, USA We report the initial six-months of a hospital—based Volunteer Program designed to serve a patient population of predominantly minority backgrounds, low socioeconomic status, and minimal personal support systems: 56% are intravenous drug abusers; 10% are heterosexual partners: and 35% are gay men. The volunteer population mirrors the composition of this patient group and 50% are patients in our Methadone Program. As of February 1987, 20 volunteers had conpleted a 2-day training program and attend weekly volunteer support groups with professional supervision of their individual work. Volunteers have provided over 1000 hours of service to over 30 different patients and have organized large Thanksgiving and Christmas celebrations for hospitalized patients. The Project's successes include: the establishment of a positive working coalition of volunteers from diverse backgrounds; the use of Methadone patients (often stereotyped, discounted and self-disparaging) to help the AIDS comnunity while increasing their own self-worth: the creation of a strong source of group support and breavement consolation for survivors of deceased patients. Program difficulties include: recruitment and selection of appropriate volunteers from a population which includes many multi-problem, poorly functioning persons: the need for safeguards against destructive experiences for patients and volunteers; adaptation of the training program and supervision to the needs of the volunteers and the hospital; and securing adequate funding for the project. The paper describes in detail the process of screening, training, on—going support and supervision of volunteers and discusses plans for future expansion. 162 TH 11 6 Hospice Care of Intravenuc m'ug Abuser AIDS Patients in a Skilled ' ' Nursing Facility. fl EHXIN, L MOWHIM, G MOIHRE, L EKXWL GH FRIEMJMHL Beth Abraham ngfital, Montefiore Medical Center/Albert Einstein Coll. of Med., Bx., N.Y., USA. Thirty two percent of AIDS patients in NYC are intravenus dig dancers (IVDA). Hospice care for AIDS patients in NYC has been limited and there is no previous experience with IVDAs with terminal illness in this setting. We report on the initial experience in hospice care for a predominately IVDA A118 population at a Skilled Mrsing Facility (31?) with a Certified auspice Program delivering home care and inpatient care. To familiarize staff with AIDS issues, a staged educational program geceded patient adnissicn. Between Fe). 1986 and Jan. 1987, 80 patients were referred aid 3 were accepted. of these 22 were male, 8 female. 22} were IVDA, 7 homaexual men, 2 sex partners of IVDA, l mkmm. Mean 3? 35, all M had AIDS dermtia complex. 'lbtal days of hospice care 867, mean length of stay 32! éys (range l-M). 83% days spent in inpatient hospice care, only 12% in home hospice care. Mean daily inpatient census, 4. Based on daily rate of $758 for acute hospital care and $346 for hospice care, estimated savings in decreased costs for 12 months, $357, 2134. Compared to other hospice patients, unanticipated problems included: (1) indfility to provide tome hospice care because of inadequate or absent housing and IVDA related social disruption, (2) continuing drug abuse, (3) increased nursing, medication, psychosocial needs, (4) difficult interactions with fmeral directors. Oantinuim fear of transmission among staff was not a major problem. Hospice care of AIDS patients in a SF is feasible, humane and cost effective. However, problems of IVDA require anecial attention and gogram modifications, if mspice care is to be [rovided for this populatim. Roundtable Discussions TH.12 People Living with AIDS: Personal Perspectives Panel Organized By: Stephen Beck National Association of People with AIDS Washington, D.C. Frederick Garnstt National Association of People with AIDS Washington, D.C. Panel Moderator: People of Color with AIDS IV Drug Users with AIDS Women with AIDS Canadian PHAs European PVAs Caribbean PHAa TH.13 Prevention of Perinatal Transmission of HIV Infection James Allen Centers for Disease Control Atlanta, Georgia Panel Moderator: Jeffrey P. Davis, Wisconsin Department of Health and Social Services, Madison, Wisconsin Howard Minkoff, Downstate Medical Center, SUNY, Brooklyn, New York Janet Mitchell, Beth Israel Hospital, Boston, Massachusetts James Oleaka, St. Michael‘s Medical Center, Newark, New Jersey Gwandlyn 3. Scott, University of Miami School of Medicine, Miami, Florida Pauline A. Thomas, New York City Department of Health, New York, New York THURSDAY, JUNE 4 TH.14 AIDS Education for the General Public Panel Moderator: Paul Kawata National AIDS Network Washington, D.C. Hillary Pickles, Department of Health and Social Security, London, England Walter Dowdle, Centers for Disease Control, Atlanta, Georgia Jan-clog Morfeldt, National Bacteriological Laboratory, Stockholm, Sweden Carol Sussman. American Red Cross, Washington, D.C. TH.15 AIDS in the Developing World (Social/Economic) Panel Moderators: Bradshaw Langmaid Agency for International Development Washington, D.C. Lair G.M. Rodrigues National AIDS Program Brasilia, Brazil Oleh Holowyna, Research Triangle Institute, Research Triangle Park, North Carolina Dr. Benjamin Here, Kenya Medical Research Institute, Nairobi, Kenya Charles Meyers, Harvard Institute for International Development, Cambridge, Massachusetts Michael Micklin, Florida State University, Tallahassee, Florida V. Ramalingaswami, Harvard School of Public Health, Cambridge, Massachusetts TH.16 Hemophilia: Where Should the Preventive Effort Be Placed? Peter Levine Worcester Memorial Hospital and University of Massachusetts Medical School and New England Area Comprehensive Medical Center Worcester, Massachusetts Panel Moderator: Peggy Heine, The National Hemophilia Foundation, New York, New York Jean—Pierre Allain, Abbott Laboratories, Abbott Park, Illinois Piero M. Mannucci, University of Milan Hemophilia Center, Milan, Italy 163 TH.17 Current Issues in Drug Abuse and AIDS Panel Organized By: Peter Bridge Department of Health and Human Services Bethesda, Maryland Panel Chairman: Roy Pickens NIDA Bethesda, Maryland John Newmeyer, University of California, San Francisco, San Francisco, California Don Des Jarlais, New York State Division of Substance Abuse Services, New York, New York Jerome Jaffe, NIDA, ARC, Baltimore, Maryland George Bigelow, Johns Hopkins University, Baltimore, Maryland Poster Session THE1 Select Lectins lnactivate HIVI_n Vitro. W. EDWARD ROBINSON, DAVID C. MONTEFIORI AND WILLIAM M. MITCHELL, Vanderbi t University, Nashville, Tennessee, USA. To evaluate the potential role of oligosaccharides in the attachment of HIV to the T4 receptor, we examined the effect of several lectins on viral infectivity. Lectins tested were 85-”, lentil, wheat erm agglutinin (WGA), hairy vetch, red marine algae, ph tohemagglutinin-P ‘IJPHAL concanavalin-A (Con-A), and succinyl concanavalin-A (sConvA). We found that at 500 nM concentrations Con-A and sCon- A preincubated with virus completely inhibited virus expression in target C3 cells as determined by indirect immunofluorescence (HF) and reverse transcriptase assay (RT). Lentil and PHA greatly diminished viral infectivity (HF and RT <20% of control) while WGA only slightly inhibited the virus (RT and HF <60% of control). 85-”, hairy vetch, and red marine algae failed to inactivate the virus at all (RT and HF >80% of control). We further found that monovalent sCon-A can prevent HIV infection of target cells significantly at a concentration of 400 nM. Since there is no relationship between lectin size and de ree of inhibition of HIV infectibility, the observed antiviral activity appears to its related to lectin oligosaccharide specificity rather than simple, non-specific stearic hindrance. Thus, these findings indicate that the oligosaccharide side chains of the HIV envelope proteins may be involved in the attachment of the virus to the T4 receptor of T-helper lymphocytes and that modulation of HIV oligosaccharides may be a useful target for the development of chemical anti-HIV agents. THRZ A Rapid and Convenient Detection of HIV by _I_n sit]; Hybridiza- tIon Using Non—Isotopically-Labelled Probes KEVIN S, BYRQN, SUSANNE M. SCESNEY, JOHN L. SULLIVAN and ROBERT H. SINGER", U. Mass. Medical School, Pediatrics and Anatomy". Worcester, MA 0l605 We have developed an 1_r1 situ hybridization methodology for rapid detec— tion of HIV in Infected cells using H9 or CEM cells as models. Cells were probed with a biotinylated DNA HIV probe followed by streptavidin and then biotinylated alkaline phosphatase (ABAP). An Intense colorimetrIc reaction 15 generated in HIV—infected cells which can be easily distinguished at cell dilutions of l X l0-5. When compared wIth isotopic probes. It was deter— mined that the sensitivity of non-isotopic detection was comparable. Using both Isotopic and non—isotopic probes we have detected HIV—infected cells In peripheral blood lymphocyte cultures within ten days of stimulation with FHA. S35—labelled probe was more sensitive for low levels of Infection, however, for routine viral isolation procedures the ABAP technique was sev- eral orders of magnitude more sensitive than reverse transcrIptase assays or RNA dot blot hybridization. We are currently studying splenic mononuclear cells (obtained from an HIV-Infected individual splenectomized for ITP) for direct visualization of HIV-Infected cells using both detection systems. In addition to HIV detection In patient samples. we have used the ABAP techni- que to develop an HIV neutralization assay. This assay can be easily quan- titated with stringent end-point titration of serum neutralizing antibody to HIV. These studies indicate that non-Isotopic l_n sItu hybridization for de- tection of HIV is~a convenient and rapid method for clinical and research laboratory investigation of HIV Infection. Supported by NIH Contract NOl—HB—67022 THURSDAY, JUNE 4 THP3 Presence of Human B-Lymphotropic Virus (HBLV) Antibody in Sera from Infected AIDS Patients DHARAM V. ABLASHI*, Z. SALAHUDDIN*, M. KAPLAN**, F. IMAM*, C. CAIN*, and R. GALLO*, *National Cancer Institute, Bethesda, MD, ** North Shore University Hospital Long Island, NY We recently described the isolation of a novel herpesvirus (HBLV) from patients with lymphoproliferate disorders as well as from 2 patients with HTLV-lII-related diseases. One hundred and twenty sera obtained from AIDS patients, 33 with lymphoma and 46 with Kaposi's Sarcoma (KS), were tested for antibody to HBLV by indirect immunofluorescence assay (IFA). Out of 120 sera from HTLV-III-related diseases, 31 contained IgG antibody to HBLV by IFA (25.8%). In addition to 220 sera from normal healthy individuals tested previously (4 contained HBLV antibody) for HBLV antibody, 80 additional normal sera were included in the present study. Among the 80 healthy donors, 6 sera were positive to HBLV (7.5%). Out of the 13 (39.3%) HBLV antibody-positive B-cell lymphomas sera, 4 exhibited strong IFA positivity to HBLV (1:40 dilutions), whereas the remainder of the positive sera were reactive at 1:20 dilution. Also, sera (32.6%) from KS patients were found to contain HBLV antibody. These results are consistent with the role of HBLV in lymphopro- liferative disorders and/or diseases of the immune system, but much more information is needed to draw any conclusions. THB4 Immunological Detection of HIV—Infected Peripheral Blood Lymphocytes RUDOLF 0.F. KUNZE and M.A. KOCH, Robert Koch-Institut des Bundesgesundheits— amtes, 100 Berlin 65, F.R.G. Virus antigen expressing cells can be detected by the APAAP-technique using a cocktail of murine monoclonal antibodies against viral p15, p210 and gpiZO. In freshly isolated peripheral blood mononuclear cells (PMC) from HIV infected persons only an occasional cell in 5000 will exhibit typical staining. If such cells are cultured for 3 days in the presence of PHA (l ug/ml) HIV antigen positive cells are demonstrable regularly with a frequency of 1:1000 to 1:100. From the results of kinetic studies of in vitro HIV infected PMC it can be excluded that the HIV infected cells observed result from infection during in vitro cultivation, i.e. either the majority of cells expressing antigens after stimulation, produce without stimulation antigen below level of detection or are latently infected. Number of CD4‘ positive cells were determined for the same samples. On the assumption that only CDA+ cells express viral antigens 1—101 of these cells are infected in the patients investigated. This suggests that number of virus bearing PMC is far greater than hitherto assumed. No correlation between number of infected cells and stage of disease was observed. THR5 MOLECULAR CLONING AND BIOLOGICAL ACTIVITY OF HUMAN T- LYMPHOTROEIC VIRUS TYPE-A. Hardy Kornfeld, Norbert Riedel, Gregory Viglianti, Vanessa Hirsch and James I. Mullins. Department of Cancer Biology, Harvard School of Public Health, Boston, MA 02115, USA. Using molecularly-cloned DNA of simian T-cell lymphotroplc virus from an African Green monkey (STLV—BAGM) as probe, we examined the genetic relationship between individual isolates of STLV-BAGM, STLV-3 derived from macaques from the New England Primate Research Center, and HTLV-A. The consensus restriction site maps for all of these isolates differed at no more than 3/34 sites examined. Strong homology, but distinct restriction site patterns were detected in cell lines infected with STLV-3 from a sooty mangabey from the California Primate Research Center and a macaque isolate from the Delta Primate Research Center, possibly infected from a sooty mangabey. Molecular clones transmissable virus of HTLV—h were obtained and shown to encode which induced formation of giant multi—nucleated cells in HUT—78, but with minimal cytolysis. Infection could be blocked by pre- treating cells with anti—CD5 antibodies indicating that H'i'LV-lo likely employs the same receptor as HIV. Comparison of the STLV-S/HTLV—A consensus with that of the LAV-2/HIV-2 reveals some restriction site conservation and sequence homology in the LTR considerably stronger than either sequence shares with HIV. 164 THRB In Vitro Mutagenesis of the HIV (HTLV III/LAV) Genome ANDREW DAYTON*. JOSEPH POTZ*, BRUCE WALKER*. TATYANA DORFMAN*, and WILLIAM A. HASELTINE**.*Dana-Farber Cancer Institute, Dept. of Biochemical Pharmacology, Harvard Medical School, and **Harvard School of Public Health, Dept. of Cancer Biolosy. Boston, MA. We have introduced a series of mutations into the HIV genome by random linker insertion mutagenesis. Our early work has concentrated on the effects of mu- tations in the integrase region of the genome, just 3' to the reverse trans— criptase gene. Cloned genomes with integrase mutations transiently synthesize a complement of viral proteins normal except for the lack of the integrase protein. These DNAs also transiently produce reverse-transcriptase—containing particles which are, however, defective for replication. Preliminary data suggests that these particles may be defective at a point past the formation of proviral DNA sub- sequent to infection. The results legitimize the integrase gene product as a potential therapeutic target. THP7 Clinical, Henatological, and Inmunological Evaluation of Individuals Exposed to Hunan T-Lymphotropic Virus Type IV (HTLV-IV) RICHARD G. MARLINK", D. RICARD**, S. M'BOUP", P. KANKI*, J.L. RDMET-LEMONND, M. ESSEX, et a ., IHarvard School of Public Health, Boston, MA, “University of Dakar, Dakar, SENEGAL. We studied various epidemiological and clinical parameters in over 300 prostitutes from Dakar, Senegal. Of this cohort, 7% were found to be seropositive for exposure to HTLV-IV as compared to a seropositive rate for the general population in Dakar of 21.5%. All prostitutes were evaluated in a clinic which serves the medical needs of this population. Follow-up has been for greater than 18 months and the seropositive prostitutes have renained without significant lymphadenopathy, without a history of chronic fevers, diarrhea, pruritis, or weight loss, and without significant differences in cutaneous anergy when compared to prostitutes seronegative to HTLV-IV. The estimated nunber of lifetime sexual contacts was comparatively increased in the seropositive prostitutes, but serology to sexually transmitted diseases and/or endenic diseases including HTLV-I was not significantly correlated with Hl'LV-IV seropositivity. Significant elevations of polyclonal 196 levels (p=.0001) and of absolute T8 lympho- cyte counts (p=.04) were found among the HTLV-IV seropositive prostitutes when compared to seronegative prostitutes and to surgical controls from Dakar. Notably, both total T cell counts and absolute T4 cell counts showed an inverse correlation to age greater than 40 years in all 3 populations, regardless of serologic status. Other significant findings were the presence of imnune complexes in at greater levels in sera of sero- positive prostitutes, as well as elevated levels of B qnicroglobulin. We conclude (1) that HTLV-IV is a sexually tra smitted virus, (2) that certain inmunologic parameters are’ consistent with a persistent viral infection, and (3) that the absence of abnormal clinical findings in this cohort over time is markedly distinct fron similar cohorts exposed to HTLV-III/HIV in Central Africa and may represent reduced pathogenicity of HTLV-IV compared to HTLV-III/HIV. THPB Anti—HIV Activity of 2',3’—Dideoxycytidine and the Unsaturated ' Derivative (2',3’—Dideoxy 2',3’dehydrocytidine) Conquered to 3' Azidothymidine (AZT). ELAINE KINNEY—‘IHOMAS", TAI—SHUN LIN“, WILLIAM H. PRUSOFF“, and ISMAIL GHAZZOULIIF *Genetic Systems Corp., Seattle, WA; MVale University School of Medicine, Pharmacology Dept., New Haven cr; ilBristol—Myers Co., Virology Dept., Syracuse, NY Anti—HIV activities of 2',3'-dideoxy 2',3'—dehydrocytidine(ddd—C); 2',3’—dideoxycytidine(dd-C), and 3' azidothyniidine(AZT) were compared in an infectivity assay which employs the LAV isolate of HIV to infect CEM cells. Virus production was monitored 15 days after infection by an EIA which uses a monoclonal antibody to capture viral core antigen (p25) and a polyclonal antiserum congugated to HRP as signal. The three compounds, when added 24 hours prior to infection at a concen— tration of 1 u“, inhibited production of detectable viral antigen when the virus inoculum was 50 TCID 50. when the inoculum was 500 KID-50, viral antigen production in the presence of 0.5M and 1M AZT was 66% and 23%, respectively, of virus control antigen levels. In contrast, ddd—C at concentrations of 0.5M and 11.114 showed complete inhibition of viral antigen production. To determine the effect of these compoimds after virus infection, an experiment was performed, allowing the virus to adsorb to the cells 45 minutes prior to the addition of the drugs. The results show that both dd-C and ddd—C at a concentration of 11.114 inhibited viral antigen production completely, even when the virus inoculum was 500 'ICID-SO, mile antigen production in the presence of ion AZT was 100% of virus control levels. This indicates that both dd-C and ddd~c are more effective inhibitors of HIV antigen production than AZT in both formats of this _i_r_i vitro infectivity assay system. other compounds have been tested, and results will be discussed. THURSDAY, JUNE 4 THEQ Detection of HIV antigen and specific antibodies to HIV core and envelope proteins in sera of patients with HIV infection. YUNZHEN CAO*, S. HOJVAT+, F. VALENTINE*, J.P. ALLAIN+, P. RUBINSTEIN**, A. FRIEDMAN—KIEN*, et al., *NYU Medical Center. New York, NY, +Abbott Labs, Chicago, IL, *‘New York Blood Center, New York, NY. We h vs tested clinically well characterized populations for 3 markers of HIV inéection; HIV antigen (HIV Ag), p24, and gp41 antibodies (Ab) to HIV. Of 56} patients, 251 were from populations diagnosed as AIDS with opportunistic infections (AIDS-OI), AIDS with Kaposi's sarcoma (AIDS-KS) and ARC. 176 specimens were from high-risk asymptomatic individuals and 136 from control subjects or patients with non-AIDS related disease. None of the 136 control individuals that we tested were reactive for either HIV Ag, or HIV antibodies to p24 and gp41. 0f the 427 HIV seropositive individuals, 99 to 100% were reactive for gp4l Ab to HIV. In contrast, we found that the sercprevalence of p24 Ab to HIV varied from 25 to 83% and appeared to be inversely associated with the severity of clinical symptoms. When specimens were analyzed for the presence of HIV Ag, we observed that in seropositive individuals, the prevalence rate for this marker was lowest (1.4%) in asymptomatic individuals and highest (50%) in the AIDS-OI diagnosed group. Also, 240 cases with AIDS-KS, OI, ARC and high-risk asymptomatic individuals group were analyzed for T4 cell number and T4/T8 ratio; only one (2.0%) HIV Ag positive case showed a T4 cell number > 400 and a normal T4/T8 ratio. These studies appear to demonstrate a direct correlation between the presence of HIV Ag and the severity of HIV infection illnesses. In one individual, HIV Ag was the only marker present, suggesting to us that in similar cases. the detection of HIV Ag may be the sole evidence for a biological diagnosis of HIV infection with current diagnostic procedures. THP10 Activity of dideoxynucleosides against HTLV-III/LAV i_n vitro ' in different human cells. CARLO r. PERNO*, R. YARCHOAN*, G. TOSATO**, D. coourv***, H. MITSUYA*, and S. BRODER’, *Clinical Oncology Program and ***Developmental Therapeutics Program, NCI, and **Bureau of Biologics, FDA, Bethesda, MD. Several dideoxynucleosides have been shown to have potent activity against HTLV-III/LAV in vitro in T cells. It has recently been shown that macrophages and Epstein-Barr virus (EBV)-infected B cells may be infected by HTLV-IlI/LAV; macrophages may be particularly important clinically. Dideoxynucleosides must undergo anabolic phosphorylation and the enzymes that mediate this may vary from cell to cell. We have examined the ability of several dideoxynucleosides to pro- tect two macrophage lines (THP-l and U-937) and two EBV-infected B cell lines (VDSO and HER) against infection with 3000 virions/cell of HTLV—III/LAV. Cultu- re supernatants were examined for reverse transcriptase (RT) and HTLV-IlI/LAV p24 antigen. 2',3'-d1deoxyadenosine (ddA) completely protected both VDSO and HER even at 5 to 10 uM. An IL-2 dependent T cell line derived from the same donor as HER, as well as the T cell lines ATHB and H9, were also protected at concentra— tions down to 5 to 10 uM of ddA. Proliferation of these B and T cell lines was not affected at concentrations up to 50 uM. Thus, ddA is effective at protecting both KEV—transformed B cells and T cells. THP-l and U-937 were completely pro- tected against infection with HTLV-III by 0.2 UK of 2',3'-dideoxycytidine (ddc), while proliferation was not affected. THP-l was also completely protected by 3'-azido—3‘—deoxythymidine (AZT) at concentrations down to 0.5 uM, while U-937 was only 85% protected at a concentration of 10 uh. Studies of the phosphoryla- tion of dideoxynucleosides in these lines are ongoing at present. These results indicate that while there may be some differences among these different human cell types, dideoxynucleosides can protect EBV-infected B cells and macrophage lines as well as T cells against infection by HTLV-III/LAV. TE'P11 Cytopsthic Effects of the Human Immunodeficiency Virus do not ' Correlate Necessarily with Cell Fusion. MOHAN SOHASUNDARAN and H.L.ROBINSON, Worcester Foundation for Experimental Biology, shrewsbury, MA, USA. To study the role of syncytium formation in the cytopathio effects of HIV infections on ru+ lymphoid cells, we followed the infection of an established laboratory stock of HIV, HTLV III, as well as a recent patient isolate, HIV(UMA-CB), on H9 cells, CEH cells, and peripheral blood lymphocyte (PBL) cultures. Virus spread and the onset of cytopsthic effects were similar in each of the HIV-infected cultures. Unexpectedly, HIV-induced syncytia were not observed except in infected 39 cells with the peak occurence of syncytia preceding peak cytopethic effects in these cells. Mixing experiments and flow cytometry were used to determine whether cell-specific expression of HIV envelope glycoproteins or density of the TM receptor determined susceptibility to HIV-induced fusion. The results of these experiments indicate that (i) actively infected cells that both do and do not undergo fusion express HIV envelope antigens which can initiate cell fusion, (ii) HIV-infected cells initiate synoytium formation more efficiently with uninfected than infected cells (presumably due to viral envelope glycoproteins interfering with the expression of TM antigen in infected cells), and (iii) the apparent surface density of it on a ru+ lymphoid cell does not determine susceptibility to HIV-induced fusion. On the basis of these results it seems likely to us that the primary cause of T-cell loss in HIV-infected patients will not be the result of HIV-induced cell fusions and that T-csll lines which undergo HIV-induced cell fusion are not appropriate model systems for the study of the loss of Th‘ cells in HIV-induced AIDS. 165 THR12 Murine Retrovirus Model Systems for Evaluating Antiviral Agents: Efficacy of AZT and ddC In vitro and In vivo. JOHN A. 31LsLL0*,", a. TRACEY‘, s. BENJERS', n. vsrrsn',". P.M. HOFFMAN , *, Research Service VA Medical Center“ and University of MarylandH Baltimore, MD. Two murine retrovirsl systems have been used to evaluate the efficacy of AZT and ddC. LP-BMS MuLV induces a lymphoproliferative/immunosuppressiva disease in adult C57BL/6 mice which has a number of similarities to human AIDS. Cas-Br-M MuLV induces a spongiform encephalopathy in NFS/N mice. In vitro studies have indicated that both AZT and ddC protect murine cells from infection with LP—HMS and Cas—Br-M and inhibit the cell to cell spread of virus. ddC was effective at 50 to loo-fold higher concentrations than reported for human cells infected with HIV. Neither AZT nor ddC reduced virus release from murins cells chronically infected with MuLV. Preliminary experiments indicate ddc was ineffective in: (a) protecting C57Bl/6 from d3 novo infection with LP-BMS (b) reducing virus load in infected mice (c) stimulating the immune response. In fact ddC appeared to depress the CTL response. AZT prevents the dissemination of Cas-Br-M HUD] and the development of neuronal degeneration in NFS/N when administered prior to or at the time of infection. Maternal transfer studies demonstrated that AZT— treated mothers transfer protective levels of AZT to their offspring. Newborn mice of AZT treated mothers challenged with loaPFU ic, had no detectible virus in their spleens or brains 3 and 8 weeks after AZT treatment. These results suggest that AZT treatment of an infected mother may inhibit viremia and protect newborns from MuLV infection. Tl1P13 Phosphonoformic acid (Foscarnet) treatment and the effect on Human ' Immunodeficiency Virus (HIV) isolation BIRGITTA ASJU*, L. MORFELDT-MANSON**,S. BERGDAHL**, J. ALBERT*, L. VRANG*, E.M. FENY6*, *Department of Virology, Karolinska Institute, Stockholm, Sweden, **Department of Infectious Diseases, Roslagstull Hospital, Karolinska Institute, Stockholm, Sweden. Phosphonoformic acid (Foscarnet) is an efficient reverse transcriptase (RT) inhibitor in vitro and it has been shown to effectively inhibit HIV infection of H9 cells in tissue culture. The strong inhibitory effect on RT in addition to a low toxicity and little side effects make Foscarnet an attractive drug for treatment of HIV infected individuals. In the present study Foscarnet was given to 8 homosexual males with persistent generalized lymphadenopathy (PGL) or AIDS related complex (ARC) as a contincus intravenous infusion at a dose of 0.14-0.16 mg/min/kg body weight/24 hours for 13-21 days. Virus isolations were initiated from peripheral blood mononuclear cells (PBMC) before treatment, the last day of treatment and at varying times after treatment. The results show that contincus intravenous administration of Foscsrnet reduced the frequency of positive HIV isolations from 13/14 (932) before treatment to 18/34 (53%) after treatment. Foscarnet had no effect on the frequency of virus isolations in patients with advanced disease. PBMC cultures from these patients regularly fieldedvirus both before and after treatment. In contrast, PBMC cultures from patients with PGL were virus negative up to 8 weeks after treatment. No diffe- rence in sensitivity to Foscarnet was noted between different HIV isolates. THP14 Isolation of a novel type of human retrovirus from ' a healthy Swiss blood donor with faint HIV p24 anti— body reaction by Western blot. JORG SCHUPBACH*, J.B. JENDIS*, C. BRON*, T. BACHI**, *Swiss Retrovirus Reference Laboratory, and **Institute of Immunology and Virology. University of Zurich, Zurich, Switzerland. Mass screening of blood donors by ELISA for HIV antibodies results in the detection of numerous individuals with repeatedly low-positive results. In at least half of these individuals, we detected faint antibodies reacting with gag proteins by Western blot. In order to investigate the origin of these antibodies, peripheral blood mononuclear cells of such individuals were routinely cultured and regularly tested for release of particu— late reverse transcriptase activity. A novel type of infectious human retrovirus morphologically distinct from all animal or human retroviruses known so far was isolated twice from a heal- thy Swiss male blood donor with a slightly positive HIV ELISA and a faint p24 antibody reaction by Western blot. The person had credibly not been exposed to HIV and had no antibodies against other human retroviruses. The presentation will include up to date information on physical, biochemical, immunologic, and biologic properties of the virus as well as preliminary data on serology. THURSDAY, JUNE 4 TliR15 HTLV-IV, LAV—2, SBL6669 and STLV—III Possess Transactivator Gene SURESH K. ARYA, BARBARA BEAVER, BARBARA ENSOLI, FLOSSIE WONG-STAAL, ROBERT C. GALLO, et al., Laboratory of Tumor Cell Biology, National Cancer Institute, NIH, Bethesda, MD. HTLv—III/LAV/HIV is the etiological agent of AIDS. It possesses a novel gene, termed ESE! which is essential for its replication and as such but indirectly may play a role in its pathogenicity. Recently, new viruses antigenically related to HTLV—III and even more closely to SmLV-III have been isolated from individuals from some west African countries. These include HTLV—IV, LAv-2 and SBL6669, isolated respectively from a lymphocytes of a healthy female prostitute, an AIDS patient, and an individual with lymphadenopathy. Some of these viruses cause immune deficiency whereas others may not. To test if the new viruses possess a ESE gene, we linked their cloned 3‘—LTRs to the bacterio- logical CAT gene. By DNA mediated transfection assays using virus-infected cells as the source of 235 function and CAT gene as the test gene, we find that all three new viruses HTLv—IV, LAV—2 and SBL6669 as well as STLV-III possess a functional £33 gene, irrespective of their pathogenic potential 12 vivo. Such structural and functional studies further suggest that (i) HTLV-IV, LAv-2 and STLV-III 3'-LTRs are structurally and functionally related, (ii) their trans- activator genes are also structurally and/or functionally homologous, (iii) their 3'-LTRs and transactivator genes are related to HTLV-III LTR and trans— activator gene and (iv) their LTRs and transactivator genes are more related among themselves than to HTLV-III. THE"; Antibody Reactions to WW9. Viruslflfinyl in 31! Infection. MARK HAKAELAN, B.Farber, M.H.Dosik*, J.Kochen, S.Katz, V.Vinceguerra. Cornell University Medical College, North Shore University Hospital, Manhasset N.Y. We studied sera from patients with HIV infection for antibody to HELV. Clarified, heat inactivated sera were reacted with phytohemagglutinin stimulated cord blood lymphocytes infected 4-5 days with HBLV (acetone fixed). Antibody was determined using fluorescene tagged goat antihuman antibody. Sera were screened for 3—4+ activity at a dilution of 1:40. 19/39 sera from patients with opportunistic infection (01), 6/12 Kaposi's sera, 40/76 lymphadenopathy sera and 2/5 lymphoma sera were reactive with over l/2 having titers of >1:160. In pts without HIV infection ,29/42 Hodgkins disease, 10/14 Acute lymphoblastic leukemia ,12/20 non Hodgkins lymphoma, 25/41 Crohn's disease,6/18 normal donors and 2/5 EBV negative sera reacted to HBLV often with titers greater than 1:160. some 4+ sera showed reactivity to uninfected PHA stimulated CBLs and to nuclear antigen (ANA). Radio-immuno-precipitation antibody assay using 35IS] methionine labeled virus and uninfected control CBLs revealed that reactive sera produced 2 bands at 96—110,000mw and at 62-66,000mw. The disease produced by this virus and its role in HIV infection and other disorders still remains unclear. This virus is however widely distributed in man as are other better known herpes viruses. THE17 Human Immunodeficiency Virus (HIV) Encodes an Alternate gag Precursor Protein of 41 kDa. SUNDARARAJAN VENKATESAN’, ERIK P. LILLEHOJ', ROBERT J. MEvas‘, HARDY CHAN**, MIKE RAUM*'*. *Laboratory of Molecular Microbiology, ’**Laboratory of Immunoregulation, NIAID, NIH, Bethesda, MD 20892; and HSyntex Corporation, Palo Alto, CA. During actue HIV infection, two 352 specific polypeptides of 55 and 41 kDa were shown to be rapidly labeled in an almost equimolar manner under pulse- chase conditions. Both of them were processed in an identical manner to mature gag polypeptides. p55 and p41 were readily expressed in a variety of non-lymphoid primate cell lines transfected with subgenomic proviral DNAs containing only the gag ORF under the control of HIV LTR, thus eliminating the possibility the p41 resulted from viral protease mediated processing of p55. p55 and p41 were metabolically labeled and purified from either persistently infected cells carrying a defective copy of proviral DNA or lymphocytes infected with virus prepared by transfection with cloned proviral DNA. Attempts at direct N-terminal sequencing of either protein failed, presumably due to blocked N—terminus. Comparative tryptic peptide mapping revealed that p41 peptide constituted a subset of p55. Four peptides unique to p55 were selected for automated N-terminal sequencing. Preliminary sequencing localized two such peptides to the N-terminal domain (residues 28-30 and 109-112) of the ggg ORE. Although the exact N—terminus of p41 was not deduced, the wieght of the evidence suggested that p41 resulted from an alternate initiation at the ME? codon at position 142 of the ggg ORE. Functional role(s) of the p41 protein are being evaluated using mutagenized proviral DNAs incapable of expressing this protein. 166 TliB18 Comparison of 6 ELISA Assays for Detection of HIV antibody in African Sera LUBAKI NDONGALA*,J. ROWLAND**,H. FRANCIS*, M.P. DUMA, M. KASALI*,T.C. QUINN** et 31., * Project SIDA, Kinshasa, Zaire, **NIAID, Johns Hopkins Univ., Baltimore, MD. African sera has been documented to cause many spurious results on ELISA assays because of immune complexes, auto-antibodies and many other immunologic reactions caused by continous exposure to endemic diseases. To systematically evaluate which tests are most effected by these conditions, we tested the Oreganon Teknika, Wellcome, Genetics Systems, Abbott, Electro- Nucleonics and DUpont ELISA assays on 300 well characterized patient sera collected at the Mama Yemo Hospital in Kinshasa, Zaire. Forty-four percent of the sera were HIV positive by western blot. The Oreganon Tecknika test was 992 sensitive and 982 specific in detecting HIV cases. The Wellcome test was 972 sensitive and 1002 specific, the Genetics Systems assay 982 sensitive and 992 specific, The Dupont test 982 sensitive and 852 specific, the Abbott test was 1002 sensitive and 722 specific and the Electo-Nucleonics test was 982 sensitive and 922 specific. The Wellcome test had the highest positive predictive value of 1002, Oreganon's was 982, ENI's was 952, Genetics Systems was 992, Abbott's was 892 and Dupont's was 822. Fifteen patients that were positive by the Dupont ELISA were asymptomatic, HIV antigen negative (Abbott), 13M negative (Dupont western blot) but p24 positive on IgG western blot. The results of the Dupont assay may represent either cross reactivity with other retrovirus infections or be false positive reactions. Almost all of the ELISA assays were able to detect true HIV infections however, in the African setting, the Wellcome test was the most rapid,(2 hours vs 4-6 for the others) and the easiest to use. THP19 Evaluation of a Latex Agglutlnatlon Assay Using Recombinant Envelope Polypeptides for Detection of Antibody to HIV THOMAS C. QUINN‘, H. FRANCIS***, R. KLINE**, M.P. DUMA***, M. SENSION**, C. RIGGIN****, et al., *NIAID, Bethesda, MD, *‘Johns Hopkins Univ, Baltimore, MD, ***Project SIDA, Kinshasa, Zaire, *“WCambrIdge BloScience, Hopkinton, MA. Screening of blood donors for antibody to HIV Is not feasible In most developing countries due to the lack of blood banking facilities and equipment, including refrigeration and ELISA readers. The cost of HIV ELISA kits and microplate ELISA readers Is frequently prohibitive and technical support Is often limited. Consequently, unscreened blood transfusions remain one of the major modes of HIV transmission In developing countries, such as In Central Africa where 5 to 15% of blood donors are scroposltive to HIV. We therefore evaluated a rapid latex agglutination slide test for the detection of HIV antibodies In order to facilitate routine screening of blood transfusions in these areas. A recombinant HIV envelope antlgen expressed In E. ill was attached to 0.5 microns latex beads, and mixed with 2.5 ul of patient sera diluted l:lO. Sera from 2,000 patients residing In Zaire, Kenya, Haiti, and Trinidad were evaluated by the latex agglutination slide test, ELISA (Organon-Teknlka) and Western blot analysis (Dupont). Overall 61m: of the sera were positive by repeat ELISA and Western blot. On a single determination for each sample the latex agglutination slide test was found to have a sensitivity of 99.1%, specificity of 99.4%, and positive predictive value of 99.5% compared to Western blot. The test was found to be simple, rapid (less than 2 minutes per test), and more specific than a single ELISA. Use of this assay will allow for the Immediate ImplementatIon of blood bank screening for HIV In developing areas of the world where standard screening procedures are Impractlcal or are not available. THBZO Humoral and Cellular Inmune Response to Recombinant HIV Glycoprote'ln, gPlZO, in Rodents and Primates. PHILLIP H. BERMAN*, T. GREGORY*, J. EICHBERG**, J. GROOPMAN***, R. HEISS****, . , at g_., Genentech, Inc., So. San Francisco, CA, **Southwest Foundation,_§an Antonio, TX,***New England Deaconess Hospital, Boston, MA, USA, ****Chester Beatty Laboratories, London, U.K. A mammalian cell line has been developed that produces useful quantities of the major envelope glycoproteln, gPlZO, of Human Immunodeficiency Virus. The recombinant protein, r-gPlZO, is fully glycosylated and able to bind to CD4 (T4) antigen with high affinity. Rodents and primates Immunlzed with r—gPlZO incorporated in an adjuvant suitable for human usage (alum hydroxide) formed antibodies that reacted with native HIV glycoproteins 9P160 and gPlZO In Western Blot and radioimmunoprecipitation assays. Sera obtained from guinea pigs, rabbits, baboons, and chimpanzees contained antibodies that were able to neutralize viral infectivity in a variety of 15 vitro neutralization assays Including: inhibition of reverse transcriptase, and VSV pseudotype assays. Chimpanzees immunized with r-gPlZO developed a cellular immune response as measured by the ability of peripheral blood lymphocytes to proliferate lg vitro in response to purified immunogen. Antibodies from several species were able to Inhibit the binding r-gPlZO to cell surface CD4 (T4) antigen in an in vitro binding assay. Finally, antibodies raised against r-gPlZO from the HTEV IIIB isolate were able to neutralize, albeit at a somewhat lower titer, a number of diverse HIV-l isolates including those obtained from Europe, Africa, and the United States. Sera from rodents and primates gave somewhat different patterns of cross neutralization, thus it appears that host factors may be important In determining the degree of protection that can be provided by a monovalent vaccine. These studies provide support for further consideration of r-gPlZO as anvaccine against AIDS. THURSDAY, JUNE 4 THP_21 Comparative Neuropathology of SIV and HIV Brain Infection. LEBN G. EPSTEIN*, L.R. SHARER‘, E.—S. CHO*, M. MMRPHEY—CORB“, 6.5. BASKIN", *UMD—New Jersey Medical School, Newark, NJ, MDelta Regional Primate Research Center, Covington, LA. A strain of simian imminodeficiency virus (SIV/Delta, or S'I'LV—III), originally isolated from a lymphoma from a rhesus monkey (Macaca mlatta), regularly produces inmme deficiency and encephalitis when inoculated into juvenile rhesus monkeys. Brains from 5 infected monkeys were compared with those of 18 children who died with human immunodeficiency virus (HIV) infection and progressive encephalopahthy. A hallmark of the simian disorder is disseminated, multinucleated, syncytial cells occuring in liver, gastro- intestinal tract, lymph nodes, spleen, and brain. Multinucleated giant cells in brain contain SIV particles on ultrastructural examination and are remarkably similar to those seen in the central nervous system of humans infected with the related retrovirus, HIV. In monkeys, these cells were predominantly perivascular, occurred in both gray and white matter and were often associated with foci of necrosis and karyorrhexis. Basal ganglia and deeper structures were frequently involved, as was the cerebral cortex; brainstem lesions were infrequent. In children with HIV encephalitis, such cells were often perivascular, but in some instances the cells bore no obvious relation to vessels. Diffuse white matter changes (pallor, astrocytosis) were only rarely observed with SIV but were common in children. One monkey had multinucleated cells in a leptomeningeal infiltrate. Complicating simian infections included simian cytomegalovirus and adenovirus. SIV infection in monkeys sufficiently mimics the human disease to warrant investigation of such pathogenetic features as penetration of virus into brain and syncytial cell formation. THRZZ Identification of Functional Regions in the HIV Reverse Transcrip- tase by Site-Directed Mutagenesis BRENDAN.A.LARDER, D.J.M.PURIFOY, K.L.POWELL and G.DARBV, The Wellcome Research Laboratories, Beckenham, Kent, U.K. We are currently studying the reverse transcriptase (RT) of HIV expressed in E.coli, with the aim of identifying those regions and specific amino acid reSidues involved in the catalytic activity of the enzyme. Initially, a large DNA fragment comprising most of the HIV pol gene, including the protease and RT sequences, was sub-cloned into an MIR—expression vector which contains the strong inducible "tac" promoter. Infection of E.coli with this recombinant bacteriophage (mpRTi) resulted in significant leve s of RT activity being induced. Through a series of manipulations, including oligonucleotide- directed deletion mutagenesis, the protease and endonuclease sequences flan- king the RT coding region have been removed, giving a construct (mpRT4) which expresses large amounts of the native enzyme. The RT expressed by mpRT4 exhibits similar properties to the “authentic" enzyme found in HIV-infected cells, including sensitivity to PFA and AZT-TP, and apparent Mr (a466 kDa). A number of regions of the RT which share homology with other polymerases have been probed by site-directed mutagenesis and using this approach, we have identified two small areas of the RT polypeptide which are likely to be involved in enzyme function, one of these being centred around two Asp resi- dues (positions 185 and 186). It is hoped that studies of this nature will provide information about the interaction of HIV RT with its substrates and may facilitate the more rational design of chemotherapeutic agents. THP23 CELL SPECIFICITY OF l-ITLV—IV AND LAV-Z PROMOTERS BARBARA ENSOLI, SURESH K. ARYA, BARBARA BEAVER, FLOSSIE VONG-STAAL AND ROBERT C. GALLO, Laboratory of Tumor Cell Biology, National Cancer Institute, NIH, Bethesda, MD. Human T-lymphotropic viruses (HTLVs) display preferential specificity for CD4‘ lymphocytes. This characteristic is partly due to the specificity of the virus-cellular receptor interaction but could also be influenced by other cellular factors and their interaction with viral promoters. We recently tested the ability of the HTLV—IV promoter to function in a variety of cell types. We linked the HTLV-IV 3‘-LTR to the bacterial CAT gene and measured the expression of the CAT gene to assess viral promoter function by DNA—mediated transfection assay. The HTLV-IV LTR-CAT DNA was transfected into human H9 and Jurkat lymphocytes, human HOS, rhabdomiosarcoma and glial cells, and hamster CHO cells. The results showed that HTLV-IV promoter functions in all cell types tested and it appeared to function more efficiently in monkey COS cells. This suggests that the HTLV-IV LTR per se lacks tissue specificity in its function as a promoter. Similar observations have been reported previously for HTLV-I and HTLV-III. THP24 HIV—2 infection in a couple of french homosexual men. G. BRUCKER*, F. BRUN-VEZINET**, MICHEL ROSENHEIM*, M.A. REY**, C. KATLAMA**, M. GENTILINI*, *Groupe Hospitalier Pitié—Salpetriere, Paris, France, **H6pital Claude Bernard, Paris, France. HIV-2 (Human Immunodeficiency Virus type 2) is a retrovirus isolated from AIDS patients from West Africa. Cross reactivity with HIV-1 is restricted to core proteins. We have identified anti HIV-2 antibodies in two french homosexual men who never travelled to West Africa. One patient has AIDS (Kaposi's sarcoma) and the second, who is his sexual partner, is asymptomatic. In both cases, ELISA for anti HIV-l antibodies was negative, Western blot only showed p 25 and p 34 in patient one, p 18 and p 25 in patient two. Those reactions, using HIV-2 antigens, were reactive ; Western blot demonstrated, in both patients, anti- bodies to p 26, p 16, p 55, gp 130-105, p 68, p 41, p 30-33. HIV—2 was isola— ted from the two patients peripheral blood lymphocytes. Since Kaposi sarcoma was diagnosed in 1985 it could be speculated that HIV-2 infection occured in patient 1 at least two years before. This suggests that, now, HIV-2 infection could be spreading in homosexual french community. The negativity of the sera by HIV—1 ELISA has been already reported. Thus, in patients with AIDS or AIDS related complex, HIV-2 infection must be sus- pected when HIV—l antibodies are lacking. A blood-bank screening test using both HIV—1 and HIV-2 antigens is now required. THP25 Comparative Quantitative Investigations on HIV-l-neutra- ' lizing Antibodies with Respect to different Epifopes BERND ZORR,K.0.HABERMEHL, Inst.of Clin.and Exper.Virology. Free UniverSIEy of Berlin, Hindenburgdamm 27, 1000 Berlin 45, Germany Quantitative determination of HIV-neutralizing antibodies is a pre- requisite for developing vaccineET‘Using a sensitive plaque reduction assay 50 sera of HIV-l-infected patients showed a linear correlation between HIV- specific antibodies on the one hand and neutralizing antibodies on the other. Since all of the examined sera without exception showed this corre- lation one can conclude that in spite of the genetic variability of HIV-l the majority of the neutralizing epitopes seems to be conserved. This in- dicates that similar as in Hepatitis B the total amount of (ELISA-deter- mined) HIV-l-antibodies gives an information about the magnitude of the humoral immune status of the patient. - Further investigations concerning single epitopes on different structural proteins have been performed using synthetic oligopeptides. One neutralizing epitope located on p 18 showed a significant concentration-dependent correlation between ELISA-reactivity (based on an oligopeptide according to this epitope) and the neutralizing activity. Since 100 % of the patients sera (n=30) showed this behaviour one may conclude that this epitope has a high genetic stability. Similar results could be obtained with an epitope from gp 4] whereas another epitope on gp 41 showed no genetic stability. The capability of the epitopes to induce neutralizing antibodies was confirmed by an antiserum obtained from sheep immunized against the corresponding oligopeptide (the synthesis of the oligopeptide and the immunization was performed by Dr.Frenzel, Biochrom). ""226 Expression in E. ggli. Purification. and Analysis of Full Length HIV £22 Anfigen D. TRIBE. B. FERGUSON. D. REED. D. MC CABE.and S.R. PETTEWAY. E. l. DuPontde Nemours. Medical Products Department. Wilmington. DE. The full length. non-fused HIV-IIIB gag gene product has been expressed at high level in E. Eli. [_E. Eli-expressed gag was obtained as a soluble protein and purified by cation exchange chromatography. Competition binding experiments indicate that all the immunoblot detectable flg-specific epitopes recognized by several AIDS patient sera are presented by full length 13. gli-cxpressed gig. Thus. this protein will clearly be a sensitive reagent for the detection of ggg-specific antibodies in human sera. An high-titer antiserum specific for full length IE. Eli-expressed HIV 3g was used to detect gag-derived proteins by Weslem blot in a licensed preparation of purified virus. In addition to p55. p24. and pl7. minor gag-derived proteins were detected at approximately I30 and 4! kDa. We note that this gag-specific rcaclivity in a Weslem blot could be falsely interpreted as HIV fl reactivity (gpl60/l20 and gp4l). In addition. HIV ggg»5pecific aniisera are being used to examine cross-immunorcuctivity between ggg proteins from different viruses. THURSDAY, JUNE 4 THR27 HIV tat/LTR- mediated Expression of Heterologous Genes. Stable— Cell Lines L. T. BACHELER, L. L. STREHL. B. Q. FERGUSON AND S. R. PETI‘EWAY. .IR., E. I Du Pom de Nemours. Medical Products Department Wilmington DE. Stable cell lines carrying a functional HIV t_at gene a reporter gene linked to the HIV LTR. or combinations of these genes have been isolated following DNA co transfectIon of appropriate plasmid constmctions and pSV2-neo as a selectable marker into HeLa cells. Clones constitutively expressing a functional gt gene product (under SV40 early transcriptional control) were identified by the ability of such clones to express a high level of chloramphenicol acetyl transferase (CAT) shortly after transfection with a HIV LTR-CAT plasmid. Clones carrying HIV LTR-CAT or HIV LTR-B-galactosidase plasmids in an activatable form express low or undetectable levels of the reporter gene protein but are readily activated to high level expression by the introduction of a HIV tat expressmg plasmid. Clones expressing high levels of 6- galactosidase under combined HIV tat/LTR control have been isolated. but no stable lines expressing high levels of CAT activity under HIV ta_t/LTR control could be derived. This observation suggests that high level expression of the CAT gene product is lethal for HeLa cells. Similar experiments using human IL-2 as a reporter gene are in progress. Our results demonstrate the derivation of stable cell lines containing heterologous genes under tight HIV Lat/LTR control. Such cell lines should be useful for further studies of the mechanism of Lat function. and for high level expression of heterologous genes in HeLa cells. Derivation of 1'"st Rapid Diret: Detaztim of HIV in Lynrhocytes of Seropositive, Asynptonatic mly $flecflNeINAAmpricathxn ._CY.(XJ*, S.MI'IGEIL*, PM. W, 5.1606, J.J. m, andG. W. *AmS Program, (Enters for Disease Omnzol, Atlanta, GA 30333. *Depsrnnnt of Diagnostic Research, Ceum Cannxatun, Emuyviue, GA9MKB. Ca-Ifirnntim of con-alt infecticn with IIIV razoira virus isolation by oomltivstion of patients' lwnixxytes with Hmbntinulated hnmfirxytes from mnnsl indivhimds. This requires up to 3 Winks with virus cxIly beirg isolatai iron 8 partial of serqxsitive irxiividuals. We have used a undified form of a DNA sIIplificatim technique to rapidly detect HIV sequenca in durnnsanfl.ENA isolataidirectly from pstients' lymixxwtes withnm prior cultivation. Two oligmer priners of 20I1cleotides emiIand an olugmer pone of 40 nucleotides from the higfly unnerved amdno tenmunm of gpkl were used. HIV semxares from petiams' lwniqute DNA were anplifiedusinglINApolynerase I inthe presence of tlewoprimers togive rise tos 135bp partial gphl sanxzks. Amplified HJV semurmes were hybridized with s 32-? evidabeled alter probe repraenting a portion of the 135 bp sequence. ’lhis was followed by digestion with Hha—I yielding a diagxstic end-labeled 24Fner. We auuyzed UWA isolated from established HIV-infected T cell lines, uninfected T cells, T cells inflxntd jilvitto with HIV, and EVA isolated directly from lymphocytes of sero- and admire-positive asymptomatic gay males frm San Francisco. We could readily detect, within 2 days, the Zh-nEr in 8 of 12 gay males tested and in all of tie infeaed T cells tut not in my of tie uninfected T cells. This technique enables us to readily identify HIV—infected persom directly. We will prwent adiitiorml data on the HIV stems fran a large water of persore wl'n are: I) mynptanatic seropositive long term survivors; 2) sew-positive but mloirefitegative persons; 3) sew-negative sputses of sew-positive perm; and lo) offspirg of sore—positive matters. THP.29 BIBERFELD GUNNEL. J. ALBERT, U. BREDBERG, F. CHIDDI, B. BUTTIGER. E. FENYD and E. NURRBV,Departments of Immunology and Virology,Nationel Bacteriological Labo- ratory, 105 21 Stockholm, and Department of Virology, Karolinska Institute, Stockholm, Sweden. Among sera tested in our laboratory for antibodies to human immunodeficiency virus (HIV) we found three anti-HIV ELISA positive sera from West African immi— grants which by Western blot (WB) and redioimmunoprecipitation (RIP) analyses reacted with gag and pol gene encoded proteins (p 24, )1, 53-55, 64) but not with envelope glycoproteins (go 41 and 120) of HIV. However, these sera reacted with envelope as well as core proteins of the West African retroviruses human T lymphotropic virus type IV (HTLV-IV) and lymphadenopathy associated virus type II (LAV—II). A retrovirus (SBL-6669) was isolated from lymphocytes of one the West African Individuals, a 55—year old Gambian woman who had a decreased num— ber of T4 cells, recurrent lower respiratory tract infections and ungal Qididky sis. Comparison of this virus with HTLV—IV, LAV—II and HTLV—IIIB by WB and RIP analysis showed that SBL—6669 virus was antigenically more closely related to HTLV-IV and LAV—II than to HTLV-IIIB. The external glycoproteins of the three West African viruses SBL—6669, HILV—IV and LAV were indistinguishable However there were interstrain differences in the size of core proteins and the pnmined transmembrane glycoproteins. SBL—6669 virus was associated with unnjrxbficiary like LAV-II (Clevel et al, Science 1986; 2}}: 343) but unlike HTLV-IV (Kanki et al, Science 1986; 232: 238). Serological comparison of human retroviruses of West African origin. 168 “"330 Immunoperoxldase Localization of Human and Simian Inununodeficlency Antigens 1n Surgical Pathology and Autopsy Specimens. JERROLD M. HARM, T.J. 0' LEARV**, R.H. RHODES***, R. E. BENVENISTE*, 6.8. and (1.6. TSAI*****, et al., *Natlonal Cancer Institute, Frederick, MD; 1"*Food and Drug Administration, Bethesda, MD; *“Un‘lverslty df Southern California. Los Angeles, CA; MMDelta Regional Primate Research Center, Covington, LA, and *****Reg10nal Primate Research Center, Seattle, WA. Surgical lymph nodes from 23 AIDS patients. fixed In 5-5, and selected autopsy specimens from 39 AIDS cases, fixed in formalin, were stained by the ABC lmunocytochemlcal technique usIng polyclonal and monoclonal antlsera to localize HIV (also known as HTLV-III/LAV) antigens Including core protein p24. Biopsy specimens with follicular hyperplas‘la had lmmunoreact‘lve v‘lral antigens In follicular dendrltlc cells, rare inmature B lymphocytes and extracellular spaces of follicles, sinus macrophages and postcap'l'llar‘y venule endothellum, while atrophled nodes were usually not tmnunoreactlve. In 2/8 cases of Kaposi's sarcoma, histlocytic cells or vascular endothelium was Inmunostained in lymph nodes with metastatic tumors. A small proportion of mult1nucleated giant cells and mononuclear macrophages were immunoreactlve 1n 8 of 15 brains with such cellular infiltrates Including 3 cases of Progres- sive Multifocal Leukoencephalopathy and in vascular endothellum of one case. Monkeys, Macaca mulatta or Macaca fasclcularis, inoculated with Simian Immu- nodeficiency Viruses l§IV III7Delta or I'llan WPRC-IJ) had viral antigens 'In macrophages, reticular cells and giant cells In sectlons of formalin fixed tissues with lymph node follicular hyperplasia, lymph node and splenic giant cell hlstlocytosls, and In retroviral encephalitis. TH231 The Acquisition of Anti—HIV Markers during Seroconversion observed in 40 High Risk Males. S. JOHNSON, WILLIAM J. MASKILL, M.J. WATERS, R.J. WARREN, BJI. DWI-JR and LI). GUST. Fairfield Hospital, Melbourne, Australia. A retrospective serological study was performed on 340 sets obtained from 39 homosexual/bisexual men and one haemophiliac male during seroconversion after infection with Human Immunodeficiency Virus (HIV). The serial bleeds from each patient were collected at random intervals over 4 years. Follow up periods from the time of seroconversion range from 3 months to 3.5 years. Tests performed on the specimens include enzyme linked immunosorbent assay (ELISA), radioimnunoprecipitation (RIP) test for anti-p24 and western blotting (NB). A 'window period' (ranging from 2 weeks to 5 months) of low sensitivity with the ELISA as compared with the WB was observed in early specimens from six patients. The earliest reactivity detected by "B was to core proteins p24, p40 and p55 followed closely by reactivity to viral enzymes (p34, p53/p68) and glycoproteins (gpAl-AS, gpllO). The RIP test was the least sensitive assay. Five patients were consistently RIP negative for all specimens, two of whom developed AIDS. These results support recent observations concerning the poor sensitivity of available ELISA's in early HIV infection during which time the NB assay detects anti-HIV core antigen reactivity. THR32 Live Vaccinia/HIV recombinant Viruses. Vaccine W‘, G. RAUTMANN”, F. PLATA**, M. GIRARD’”, L. MONTAGNIER”, J—P. LECOCQ,'Trsnsgene S.A., Strasbourg, France, ”Institut Pasteur, Paris, France, *‘*Pasteur—Vaccins, Marnee La Coquette, France. Both HIV lentivirusee and HIV—infected cells are presumed to present a single major target antigen at their surfaces. This polypeptide, the 22x glycoprotein. is thought to promote HIV infection by interaction with a host protein, possibly the lymphocyte T4 antigen. The 160 kilodslton 52x precursor glycoprotein (gp160) undergoes proteolytic cleavage in vivo, yielding a gpdl transmembrane moiety and a gp120 extracellular component. By analogy to the gp's of similar viruses, these have been presumed to remain associated at the cell surface. We have expressed the HIV :2! gp160 precursor glycoprotein gene in a recombinant vaccinia virus. £21 glycoprotein encoded by the recombinant virus VVTGeLAV is correctly cleaved to generate gp41 and gp120. However, the two moieties do not remain associated, gp120 being rapidly shed from the cell surface. We have constructed mutants of VVTGeLAV in which the 221 cleavage site(s) has been removed, and the immunological properties of these second— generation recombinants will be discussed. An approach to an AIDS THURSDAY, JUNE 4 THP33 LAV—2/HlV-2 infection : Clinical, epidemiological and virological features FRANCOISE BRUN-VEZINET‘, M.A.REY‘, M.C.DAZZA', S.GADELLE", J.J.MADJAR“‘, M.HARZ|C', at al. Laboratoire de Virologie, hopital Claude Bernard’, Paris; Diagnostics Pasteur“, Paris; Université Alexis Carrel‘“, Lyon — France. In 1986 we diagnosed 18 cases of LAV—2/HlV—2 infection in patients (pts) who have been living in France for at least one year. Six pts were assumed to have AIDS whose 2 met the criteria for AIDS since 1983. Two pts presented with ARC diagnosed in 1985. Ten were asymptomatic subjects (AS). Eleven pts originated from West African countries : Cape Verde islands (2), Ghana (3), Ivory Coast (1), Guinea (2), Senegal (2) and Guinea Bissau (1). Seven pts were european : 2 heterosexual Portuguese couples, one French heterosexual male and a French couple of homosexual males. In these pts, HIV—2 transmission was likely to be acquired through heterosexual or homosexual contacts. None was a drug abuser. In the 2 heterosexual Portuguese couples, the mode of HIV-2 transmission is quite unclear. Vertical transmission is studying in 3 cases of HIV—2 pregnant women. Retrovirus isolation was performed from the peripheral blood lymphocytes from the 12 tested patients (5 AIDS, 2 ARC, 2 AS). In the supernatants of the cultures, an antigen capture assay using HIV—1 polyclonal antibody did not detect HIV-2 antigens. Isolates were characterized by Dot Blot hybridization with HIV-1 and HIV—2 DNA probes. Weare performing Southern Blot analysis of isolates from patients originating from different countries. HIV—2 neurotropism was demonstrated by virus isolation from the CSF and/or by intrathecal lgG HIV—2 synthesis. IgG antibodies to HIV-2 were detected by Elisa and WB (Diag— nostics Pasteur). Since the HIV-1 and HIV—2 cross—reactivity was restricted to the core proteins, only the presence of antibodies to HIV—2 envelope glycoproteins demonstrated HIV-2 seropositivity. Whatever HIV—1 and HIV-2 common characte— ristics, as lymphotropisrn and cytopathic effect in vitro, question is asked about a difference of pathogenicity. THP34 Evaluation of Microinjection of Cloned Genes as an Effective Method ' of Genetically Engineering Mammalian Cells to Produce Human Immuno- deficiency Virus and Envelope Protein V. ANN BOYDt, T. G. WOOD)”, R.V. GILDENHHI, and M.A. GONDMI, *Laboratory of Cell and Molecular Structure, and “Recombinant DNA Laboratory, tnProgram Resources. Inc., NCI-FCHF, Frederick, MD. A cloned HIV, strain HTLV-IIIB (pHXB-Z), infectious provirus was microin— Jected into the cell nucleus of six non-lymphoid cell lines from caprine, ovine, bovine, and human species. For each cell line, 100—200 cells were microinjected with pHXB-Z. An immunofluorescence assay (IFA) for HIV p24 demonstrated virus replication 24—48 hrs after microinjection in 5% of the cells. Virus was recovered from all cell lines regardless of tissue or species of origin by cocultivating T4—positive human lymphocytes (H—S) with the microinjected cells 48 hrs after microinjection. Confirmation of infectious virus release from injected cells was demonstrated by syncytia formation, electron microscopy, reverse transcriptase, and radioim-unoassay for HIV p24 in cocultures. Syncytia in cocultivated H—9 cells were apparent on days 7—10 and was both the earliest indicator and most reliable assay for demonstration of infectious virus release. A complete envelope subgenomic fragment of pl-lXB-Z flanked by 5’ and 3’ L'l'fls (pLVWT) was constructed and introduced into mammalian cells in an attenpt to create a cell line expressing high levels of the HIV envelope free of infectious virus. Using an antiserum to gplZO, the major outer envelope protein of HIV, 5—2096 of the microinjected cells were found to express low levels of envelope proteins by IFA. No replicating virus was detected and the duration of upression has not yet been determined. These results suggest a possible approach to producing antigens in mamalian cells and may have relevance for vaccine development. THR35 HIV Neutralizing Antibodies and Cellular Imnmity Elicited by a Recurbinant Virus Envelope Produced in Insect Cells Cm 1111 J'EIIJS*, J. WSCHE", K. KRDHN**, T. W***, M. W**, S. HH‘NEY‘, et al., *Repligen Corporation, me Kendall Square, Building 700, Cambridge, MA, *flaboratory for Tumor Cell Biology, National Cancer Institute, National Institute of Health, Bethesda, MD, ***Department of Surgery, Duke University Medical School, Durham, NC. The HIV envelope (gp160) was produced in insect cells using a baculovirus expression vector encoding the HTLV-III envelope. Antibodies frcm animals J'mmnized with this protein neutralize HTLV-Illa virus and the neutraliza— tion titer of this antisera is approximately five—fold higher than that of antisera to native gplZO isolated frun the virus. The neutralization of the gpl60 antisera is type specific in that it does not efficiently neutralize the heterologous variants, l-l'I'LV-IIIMN and H'I'l’N-III . In addition to eliciting a Immoral inmune response, gplGO elicits cell imnunity as treasured by T-cell proliferation upon stixmlation by virion or native gplzo. In contrast to the Mmral response, cellular immunity is not HIV isolate specific. We arepreparingtheenvelope frmotherviralvariantstoobtainamrehroadly neutralizing responseand to evaluate these proteins as a vaccine. 169 THR36 Isolation and Characterization of a Bacterially Expressed Reverse Transcription of HTLV III/LAV Karin Moelling, J. Hansen, T. Schulze, and S. Sukrow, Max—Planck—Institut ffir Molekulare Genetik, Abt. Schuster, 1000 Berlin 33, IhnestraBe 73, Germany. Various fragments of the "pol" region of HTLV III/LAV were cloned into different expression vectors. Enzymatically active reverse transcriptase was detected with two of them in transformed bacteria. Furthermore, two protein bands of 66 and 51 kD were de- tected in bacterial lysates using patient sera suggesting that they represent the reverse transcriptase subunits fl and a. Pro- cessing from larger molecules, which presumably represent precur— sor forms, could be followed with time. The enzyme activity was purified by means of DEAE-Sephadex, phosphocellulose, mono S and immuneaffinity column chromatography. Biochemical parameters of the bacterial polymerase were compared with virion-associated reverse transcriptase. Inhibitor studies as well as fidelity stud- ies were performed and will be presented. The enzyme should be useful for large scale screening of reverse transcriptase in- hibitors. THR37 Inactivation of HIV by Disinfectants and Spermicides VVETTE HENIN, V. MARECHAL, F. BARRE-SINOUSSI and J.C. CHERMANN, Institut Pasteur, Viral Oncology Unit, Paris, France. Various disinfectants and spermicides have been tested for their efficacy to inactivate in vitro the reverse transcriptase and the infectivity of HIV for human peripheral Blood lymphocytes. Disinfectants commonly used in hospitals for cleaning floors and benches were containing alcohol in quaternary ammonium or aldehyde complex solutions or glutaraldehyde in quaternary ammonium solu— tions. All these solutions were found to be effective either undiluted or at concentrations ranged between 0.25 % and 25 % with a time of treatment varying from 1 to 10 min. at room temperature. Disinfectants for medical instruments were mainly aldehyde solutions and were also destroying viral activities. Com- mercialized solutions for body hygiene are often a mixture of alcohols with other compounds such as quaternary ammonium salts or chlorohexidine for exam- ple. Five of them were tested and found effective at various concentrations (0.5 % to 50 %) in a short time of contact with the virus (30 sec. to 5 min.). Inactivation of HIV by spermicides containing cationic detergent (benzalko— nium chloride or alkylbenzyldimethyl ammonium chloride) has also been shown to inactivate HIV infectivity in vitro at low concentrations in a relatively short period of treatment (10 to 60 m1n.). The effects of other spermicides and disinfectants will also be discussed. These results might be of interest for the prevention of the sexual transmission of the disease and for the sa- fety in hospitals and laboratories. THEsa A maximum. ANTIBODY m (INHICALLY ENGINEERED [DI—GLYCOSYLATED GPlZO PRODUCED Ill YEAST NEUTRALIZES HIV. J.C. STEPHANS and K.S. STBIHBR. Chirou Corporation, Eleryville, California, U.S.A. A murlne monoclonal antibody specific for a genetically engineered polypeptide produced in yeast corresponding to amino acids 28-491 of the envelope gene product of the ARV-2 isolate (now designated HIV-SFZ) of human immunodeficiency virus (HIV), is able to neutralize the infectivity of HIV-SFZ 12_vi:ro. This monoclonal antibody, referred to as 95C9, reacts with glycosylated HIV-SFZ gp120 in immunoblot assays. In addition, it also reacts specifically in immunofluorescence assays with acetone-fixed HIV-SFZ-infected cells. By using recombinant HIV-SFZ antigens corresponding to subreglons of gp120, 95C9 was shown to react with an epitope between amino acids 28 and 277 of the HIV-SFZ 32! gene product. Assays with other HIV isolates, showed that 95C9 was reacting with an epitope that was not conserved among all HIV isolates; 9569 did not react in either immunoblot or immunofluorescence assays with HIV—Zr6 or LAV-FRU, two virus strains which show considerable divergence from HIV-SFZ in their gplZO coding regions. Neutralization assays with these two isolates, and other HIV strains, are in progress. In addition we are attempting to map the precise location of the 9SC9 reactive epitope. THURSDAY, JUNE 4 THE39 Stability of RNA stem—loop Structure and Distribution of Non-Random Structure in Human T-cell Lymphotropic Virus Type III SHU—YUN LE. J—H. CHEN‘, J.V. Maizel, Jr., Laboratory of Mathematical Biology, NCI, NIH, *ASCL NCI/FCRF, Frederick, MD. The stability of predicted RNA stem-loop structure in human T-cell lympho- tropic virus type III has been tested statistically using a Monte Carlo simula— tion method. The distribution of statistically significant stem-loop structure have been obtained. We can find the characteristic patterns in the 5' non—coding region, boundary region between the protein coding frames and 3' non-coding region. Especially, the size of the distinct and significant secondary structure occurring in the 5' terminal region has been assessed under different window sizes using Monte Carlo method above. The predicted secondary structure with about 100 nucleotides is preferable to those with other size in 5' non—coding region. Moreover the distributions of significant stem-loop structures in the 5' terminal of ARV—2, LAV and H9/HTLV—III have also been computed. The possible correlations between the AIDS virus genome biological function with the pre- dicted non—random, significant stem-loop structures are discussed. Our results support recent experiment results, in which the possible stem-loop structure of the 5' region of HTLV-III mRNA is involved in translational control. Tests for Virus Yield Control in HIV Infected Cell Culture During Preparation of Test-System for AIDS Serodiagnostics . O.G.ANZDZIAPARIDZE, SVETLAN SJARENNIKOVA §.R.HATSEVIGH, L.G.STEPANOVA, 5.x. an 6v Institute of Viral Preparations, 0.8.8.12. Conventional variant of immune-enzyme test-system based on pu- rified and concentrated HIV antigen has been developed. To obtain the antigen, HIV strain IVA 85 isolated at the Ivanovsky Insti- tute of Viroloy in 1985 and adapted to continious lymphoid cell line has been used. During productivity control of chronically infected IVA 85 culture for cell fraction control, electron microscopy, indirect immunofluorescence, and immune-enzyme assay with cell suspension adsorbed on plates or their lysates in ve- rious concentrations were applied. HIV antigen in liquid fraction was determined by i BIA-capture with human 156 to HIV adsorbed on plates and with the same antibodies labeled by horse-radish peroxidase, ii indirect EIA with the adsorbed on the plates dilutions of 100—fold concentrates of cultural fluid. Along with that, rate of virus accumulation in the cells in cul- tural fluid was evaluated by hybridization with molecular probe. Complex of the methods used gave possibility to choose an op— timal passage scheme. Until now, IVA 85 culture passed 70 con- sequent passages without fresh lymphoid cells addition with 70-85% of antigen-containing cells. Data of examination of 600 sera prove system specificity to be 99.64005. THR40 Institute of Virology, Moscow, THR41 Bacterial Pneumonia and HIV Infection in Parenteral Drug Users witmut AIDS PEHR A SELWYN, AR FEHIXXDI D HNUILI EE ssixounnn, GH FRIEIJNDIMP ALDERMAN, et a1, Montefiore Medical Ctr/Albert Einstein Cbllw Medicine, Bx, NY; USA. Epidemiologic data from New York City (NYC) demonstrate a sharp increase in man-AIDS pneumonia deaths among intravenous dru; abtmers (l'VDAs) since 1981. We studied the incidence of bacterial pneumonia in a well-defined powlatim of IVDAs without AIDS, and examined the association with HIV mtibody (Ab). All inspitalizations over a 12 mmth period were monitored among 436 IVDks in a NYC methadone program (MM'IP) enrolled in a prospective study of HIV infection. Hospitalizations were identified through active surveillance by MMTP staff. Both MMT? and hospital staff were blinded to patients' HIV Ab statusn Hospital charts were reviewed for all pneumonia cases. Pneumonia was defined by infiltrate on chest x—ray; organisms were identified by Gram stain, blood and/c: sputum culture, or serology. Surveillance began 12/1/85. At entry, there were 159 seropositives (SPs) and 277 sermegatives (Sis). By 9/30/86, 115/159 (72%) SPs and 26/277 (85%) Sis remained in the MM'I'P (p<.05). Over 12 months, 14/159 (9%) SP5 vs. 6/277 (2%) SNs were hospitalized for bacterial pneumonia: odds ratio (O.R.)=4.4 (C.L. 1.6 - 11.6, “0.005). Inthe 3’ grotp organisms were Hemophilus influa'lzae (6), Stryoooccus pneumoniae (5), Staphylococcus aureus (1), Escherichia coli (1), and Legionella 55% (1). In the 3‘] group, organisms were _H._ influen7ae_(4), S. Eunauae (l) K 1e11a Egumoniae (1). ’Iwo cases in SPs were fatal vs none E Sis. Pneumonia was more highly associated with HIV Ab in patients reporting no current IV drug use: for those not using drugs at study entry, O.R.=6.7: for those still using, 03520. Itese results indicate a remarkably high incidence of bacterial pneunonia anrxg SP IVDAs without AIDS (minimum yearly rate = 88AM), with a case—fatality rate of 2/14 (14%). Association with HIV Ab was not attributable to increased drug use among SP5. The high freqzency of infection with i Eumoniae and i fllwnzae suggest tie need for study of immmimtion of SP IVDAs against these patl’ngeris. 170 THR42 Human Immunodeficiency Virus Viremia in Homosexual Men with Lymphadenopathy JONATHAN E. KAPLAN, T.J. SPIRA, P.M. FEORINO, D.B. FISHBEIN, D. WARFIELD, Centers for Disease Control, Atlanta, GA. Seventy-five homosexual men with lymphadenopathy syndrome (LAS), defined as lymphadenopathy in 2 or more extrainguinal sites for >3 months, were enrolled in a prospective study in Atlanta in 1982:1983. All were seropositive for antibody against human immunodeficiency virus (HIV). As of January 1987, 16 (21%) of these men have developed the acquired immunodeficiency syndrome (AIDS). Cultures for HIV were performed on lymphocytes from 109 peripheral blood specimens from 66 of the 75 study participants, including 12 who subsequently developed AIDS. Cultures were screened for up to 4 weeks for reverse transcriptase (RT) activity. of 23 men with positive results (defined as 210000 RT counts/0.4 m1) on the first sample, 15 were cultured a second time; all but 2 remained positive. of 43 men with negative results on the first sample, 12 were cultured again up to 36 months after the first sample was obtained. Three were positive on the second sample and 3 others on the fourth; 6 have remained culture negative in up to 5 specimens. Men who were initially culture positive and men who were culture positive on any occasion were more likely to progress to AIDS than culture negative men (9/23 vs. 3/43, p=.002; 10/29 vs. 2/37, p-.003; respectively). Culture positivity is a marker for progression to AIDS and is likely to develop in most men with LAS. The confidence that there exists a subgroup of men that remain culture-negative and have a better prognosis is diminishing with time. THP43 Frequency of Clinical and Laboratory Abnormalities among HIV . Antibody Seropositive and Seronegative Gay Men. WALTER KRAMTF, D.OSMOND, P.BACCHETTI, A.MOSS, UCSF and SFGH, San Francisco, CA, USA. We report frequency of clinical and laboratory abnormalities among subjects seropositive and sercnegative for HIV antibody in a prospective study of three groups of gay men in San Francisco: an STD clinic group, a randomly selected neighborhood group, and sexual partners of men with AIDS. Of 320 subjects seen at one—year followup,64% (205/320) were seropositive for HIV antibody by ELISA with Western Blot confirmation. Oral candidiasis and oral hairy leukoplakia were clinical findings observed only in seropositives, 9% and 3% of seropositives, respectively. Three laboratory measures were seen only in seropositives: platelet count 5 120,000 (9% of seropositives), ESR Z 22 (92), and H/S ratio S 0.6 (35%). Generalized lymphadenopathy was found in 55% of seropositives and 12% of seronegatives. Frequency of other measures in seropositives and seronegatives, respectively, are as follows: shingles, 10% and 5%; hemoglobin s 14.2, 23% and 3; WBC < 4.6, 37% and 9%; lymphocytes S 1500, 21% and 7%; and absolute T-helper count 5 400, 32% and 3%. H/S < 1.0 was found in 55% of seropositives and 15% of seronegatives, whereas H/S $.1'5 was found in 72% of seropositives and 71% of seronegatives. A significantly higher percent of seropositives in the STD and partner groups had an H/S ratio <1.0 (61% and 58%) than in the randomly selected group (38%) (p=0.008), indicating possible greater duration of infection in those groups or cofactor effects or both. Supported by a grant from the Universitywide Task Force on AIDS. THR44 HIV Seroprevalence Among Connecticut Intravenous Drug Users in 1986. RICHARD D'A UILA*, A.B. WILLIAMS*, L.R. PETERSEN**, A.E. WILLIAMS*** *Yale University, New Haven, CT., **Centers for Disease Control, Hartford, CT., ***American Red Cross, Bethesda, MD., U.S.A. The rising seroprevalence of HIV infection among Connecticut intravenous drug users (IVDU) in 1986 was monitored by anonymously testing all admissions to selected drug treatment programs for HIV antibody. The largest number of sera (171) were obtained from entrants to the New Haven Substance Abuse Treatment Unit. In 1986, 22.2% (38/171) of those seeking treatment for active intraven— ous drug use were Western blot (WE) confirmed HIV seropositive. Interview questionsire data on 114 of these entrants have been analyzed. Significantly more of the blacks (81.8%-l8/22) and of the Hispanics (40%-2/S) than of the whites (10.4%-9/86) were NB seropcsitive (p<0.0001, chi-square) among this 76% white group. Seropositives were older (mean-33 vs. 30 years, p<0.007, t—test) and had a longer history of drug injection (mean—14.3 vs. 10.6 years, p-0.03, t-test). There was a non-significant trend toward more needle uses in the past year among seropositives. Sixty-eight percent (76/112) had shared needles in the past year. There was no association between sharing and seropositivity or between sharing and race. Most attempted to clean shared needles. HIV seroprevalence and interview data were assessed in an additional 147 en- trants to methadone programs in 3 other Connecticut metropolitan areas. For entrants to all program locations, including 114 from New Haven, seroprevalence decreased with increasing distance from New York City (p<0.01, Mantel test for trend). Stratified analysis, controlling for program location, showed that blacks (odds ratio-15.0, 95% confidence interval (CI)-7.l-33.0) and Hispanics (odds ratio—8.8, 95% CI-2.6-30.4) were significantly more likely to be sero- positive than whites (p<10_ and p<0.01, respectively, Mantel-Haenszel chi- square)- THURSDAY, JUNE 4 THB45 Cause-Specific Mortality Rates for the Acquired Immune Deficiency Syndrome (AIDS) Dade County, Florida 1985. DAVID G. WITHUM‘, D. HOLTZMAN*, R.STEVENS*, G.METELLUS*, J.SIMS*, J.WITTE*, et al., *AIDS Program, Florida Department of Health and Rehabilitative Services, Tallahassee, FL. Dade County, Florida, which encompasses the greater Miami metro politan area, is situated in the lower southeastern portion of the State of Florida. As of January 23, 1987, 869 cases of AIDS, with Dade County morbidity, had been reported to the AIDS Program, State Health Office, Department of Health and Rehabilitative Services, Tallahassee, Florida. To assess the impact of this disease for 1985 in Dade County, deaths attributable to AIDS were identified. The Florida AIDS case registry, death certificates, and medical examiner logs were reviewed and 145 of the 17,324 total 1985 Dade County deaths (0.83) were classified as AIDS deaths. Dade County 1985 midyear population estimates (white 1,305,282; non-white 461,670) were used to establish crude cause/race— specific mortality rates. The crude AIDS cause specific mortal- ity rate for Dade County was 8.2 deaths per 100,000 population. AIDS mortality by race consisted of 77 non—white and 68 white deaths. Population adjusted data developed a 3.2:1 non-white/ white ratio. There was a statistically significant difference between non-white/white deaths 16.7/5.2 per 100,000. (p<.05). These mortality rates were compared to other leading causes of death in Dade County. AIDS non-white deaths exceeded deaths due to motor vehicle accidents (16.7/13.4 ger 100,000) and ap roached white homicide deaths (18.9 per 100,00 ) for Dade County 985. THB46 Prevalence of Human Immunodeficiency Virus (HIV) Infection in Ethnic Minority Homosexual/Bisexual Men. MICHAEL C. SAMDEL, W. HINKELSTEIN, JR., School of Public Health, University of California, Berkeley, CA. Of 1034 participants in a randomly selected prospective cohort of single men between the ages of 25 and 54, 816 (78.9%) are homo/bisexual and of these 100 belong to ethnic minorities. We examined four minority groups and the only significant differences in prevalence or incidence of infection were between black and white men. We observed a higher proportion of HIV infection among blacks, 19 of 29 (65.52) than among whites, 341 of 700 (48.7%). Blacks also experienced a higher rate of HIV seroconversion than whites during the 2A months of follow-up; among the 10 HIV seronegative blacks who entered the study, two (201) became infected while among 359 seronegative whites, 23 (6.4%) became infected. To explain these findings, three established risk factors for the transmission of HIV infection—-needle sharing, multiple sexual partners and frequent receptive anal/genital contact--were examined. Whereas a slightly higher proportion of whites shared needles and had multiple sexual partners than blacks and a slightly higher proportion of blacks had frequent receptive anal/genital contact than whites, none of the differences were significant. Available measures of socio-economic status also did not differ by race. Other reports have indicated that blacks are disproportionately represented among AIDS cases nationally, and they have suggested that the findings are due to increased prevalence of IV drug use. Here, needle use does not explain the difference; our findings suggest the need for further investigation into the role of race and HIV infection. THE47 Risk Factors for Seroconversion with Human Immunodefiency Virus Among Homosexual Men in San Francisco, 1983-1987. RUTH M. GREENELATT’, M. SAMUEL**, D. OSMOND***, W. WINKELSTEIN**, J.A. LEVY***, A. MOSS***, *Robert Wood Johnson Clinical Scholars Program, San Francisco, CA, **U.C., Berkeley, CA, ***U.C., San Francisco, CA. Two prospective studies in San Francisco have identified 37 homosexual or bisexual men who developed serum antibodies to human immunodeficiency virus (HIV) during study surveillance, 1983-1987. In the year prior to acquisition of HIV antibody, 74% of seroconverters reported receptive anal intercourse, 77% reported insertive anal intercourse and 100% receptive oral intercourse. Sixty-eight percent reported using drugs during sexual activity. when compared to HIV seronegative controls, men who acquired antibody had a greater number of male intercourse partners (p(.0001), and were more likely to have reported: receptive anal intercourse (p-.009), receptive oral intercourse (p-0.04) and use of either cocaine, amphetamines, depressants, or hallucinogens during sexual activity (p=.0005). When entered into logistic analysis with number of sexual partners and specific sexual practices, use of the above drugs was significantly associated with antibody to HIV (odds ratio 3.29, p=0.01). of nine men who denied receptive anal intercourse in the year prior to HIV infection, seven reported insertive anal intercourse. The two men who denied both practices recalled receptive anal intercourse in the preceding 18 months. Eight of these nine men acquired antibody late in the studies. The proportion of men who acquire HIV infection through receptive anal intercourse may be decreasing, and less efficient modes of transmission may become more apparent. Use of drugs during sexual activity may contribute to risk of HIV infection. N1 THP48 Male-to-Female Transmission of Human Immunodeficiency Virus (HIV): Current Results, Infectivity Rates, and San Francisco Population Seroprevalence Estimates. NANCY PADIAN*, J. WILEY*, W. WINKELSTEIN*, *U.C., Berkeley, Berkeley, CA. Eighty-nine female partners of men who were infected with HIV or diagnosed with AIDS or ARC have been interviewed and tested. More than 502 were the partners of bisexual men. Overall, 201 of the women were infected (95% confidence interval: 131-302). Based on the reported number of sexual contacts with the infected partner, we were able to calculate a per exposure infectivity rate of .001 (95% confidence interval: 0-.0024). However, the infectivity rate was almost 1.8 times higher for women who practiced anal intercourse than for those who practiced only vaginal and oral sex. This higher rate is comparable to the anal—receptive infectivity rates reported for male-to'male exposure. Using these estimated infectivity rates in conjunction with survey data on the number of male partners of heterosexually active women in San Francisco, combined with estimates of seroprevalence in their male partners, we project that approximately 4 of 1000 such women may have been infected by these men. We conclude that penile-vaginal contact, a well documented risk, is a less efficient means of transmission than is penile—anal intercourse. Higher rates of heterosexual transmission reported elsewhere are probably attributable to factors such as greater numbers of exposures (sexual contact with an infected partner), parenteral exposures, or to other co-factors and behaviors not prevalent in this sample. THR49 Natural History of HIV Infection in a Cohort of Homosex— ual Men from Los Angeles. ALEXANDRA H. LEVINE, PARKASH S. GILL, MARK KRAILO, MARK U. RARICK, CARMEN LOUREIRO, SURAIYA RASHEED et al. University of Southern California School of Medi— cine, Los Angeles, California. 63 patients with biopsy—proven persistent, generalized lymph— adenopathy (PGL), and 67 asymptomatic gay control men were evalu— ated every six months with serial repeat node biopsies, HIV and EBV serology and virology, and immunologic function. Median follow—up interval is 1.3 yrs (0-53 mos). Mean age of pts was 32.4 yrs, vs. 34.7 yrs in controls. In the PGL cases, 73% were white, 13% black, and 15% Hispanic. At study entry, 62/63 (98%) PGL cases were HIV seropositive, vs. 36/66 (55%) of gay controls (p<.05). With follow—up, 2 additional controls have become HIV positive and all PGL cases are HIV positive. Rates of conversion are as follows: Conversion from Conversion from Conversion from HIV— to HIV + Control=7.1%/person—year HIV + control to any ARC=17.3%/person-year HIV + control to PGL=7.4%/person-year Conversion from PGL to any AIDS condition=9.2%/person—year Conversion from PGL to lymphoma=3.9%/person—year Two variables were significantly (p=.01) associated with increased risk of conversion from PGL to lymphoma: increased gamma globulin fraction, and increased IgG level at PGL diagnosis. Three variables significantly associated with increased risk for conversion from PGL to AIDS were (1) decreased T4, (2) decreased T4/T8 and (3) increased IgA, at time of PGL diagnosis. Laboratory and Clinical Manifestations of HIV Infection in Patients wuth Congenital Clotting Dlsorders (COD) THRSO GEORGE L; G R ETI, The TranstSIon Safety Study Groups II, uPuget Sound Blood Center. Seattle. WA, USA, Inother partucnpatnng Institutions. The Transfusion Safety Study is a multicenter cooperative evaluatnon of factors InfluenCIng risk of transfusion-transmitted fill infectuon and pro- gressnon. TSS has clinical and laboratory data on 456 treated 060 patients (426 male. 20 female). of whom 552 are antl-flll(+). We recorded clinical signs (unexplained weight loss or diarrhea. generalized lymphadenopathy thrush or roster) and laboratory findings (platelets < (00K. lymphocytes < 1000 or T4 lymph: < 200). A higher percentage of anti—fi11(#) patvents (l9Z vs 2%. P<.OO1) had one or more abnormal findings. Three patients had AIDS. Lymnnadenopathy was the only clinical sign sugnufvcantly more frequent In anti—flii(+) patuents (P=.007). Among laboratory findings both lymphopenia and low T4 counts were more fre- quent an anta-fii1(~) patients (p<.001). Anti-fil1(+) patients were IiKeller to have lymphopenla If 15+ years and low T4 oountl If 35+ years. The likelihood of manifestation: In anti-HIV(+) patients did not appear to depend on type of treatment (factor B or 9 concentrates or single donor components). These data show that, thus far, most anti-HIV(+) CCD patients are clinically well though they may have laboratory manifestations of H V Infection. (Supported by Con- tract No. NOl-HB-4-7003 o? the National Heart. Lung and Blood lnstntuteJ THURSDAY, JUNE 4 THP51 KEEEAEENCE OF HIV ANTIBODIES AMONG INTRAVENOUS DRUG USERS IN LOS L LOREN LIEB*, L. MASCOLA*, L. WUODARD**, D. MC ALLISTER**, M. GILES*, S. FANNIN*, ET AL., *Los Angeles County Department of Health Services, Los Angeles, CA, **Los Angeles County Drug Abuse Program Office, Los Angeles, CA, USA Although Los Angeles County has the third largest number of AIDS cases nation- wide, the percent of AIDS cases who are Intravenous drug users is low (11%) com- pared to the East Coast rate of approximately 70%. To assess the prevalence of HIV antibodies in our intravenous drug addict population a random sample of 728 individuals, enrolled in either methadone maintenance or detox1f1cation programs, were interviewed between April and July 1986. Detailed demographic data, medical, sexual and drug use histories were ob- tained, and blood was drawn for determination of HIV antibody status, markers for hepatitis B, and VDRL. Only 13 (2%) part1c1pants were seropOSItive. Sixty- nine percent of the positives were white compared to 5 % of the negatives; 23% were hispanio compared to 3A% of the negatives; the percentage of Blacks in both groups was the same. Seven of the HIV antibody paeltives were male, of whom 5 were homosexual or bisexual. Of the 6 pOSItive females, 3 admitted to prostitution. Although the seroprevalence is extremely low, 9 % of the sero— posltives and 96% of the seronegatives admitted to sharing needles. Therefore, timely education efforts must be targeted to modify these high risk behaviors before the prevalence rate rises precipitously. THEsz Screening of U.S. Populations for the Presence of LAV—II G. SCHOCHETMAN, PH.D.*, C.A. SCHABLE, M.S.*, L.C. GOLDSTEIN**, J. EPSTEIN, M.D.*** and T.F. ZUCK, M.D.***, *Centers for Disease Control, Atlanta, GA, **Genetic Systems Corporation, Seattle, WA, ***Food and Drug Administration, Washington, D.C. A new human retrovirus was isolated from people in West Africa and Europe by scientists at the Pasteur Institute, Paris, France. The virus, designated as LAV II, appears to be transmitted in a manner similar to Human Immunodeficiency Virus (HIV) and cause similar symptoms. A preliminary study was conducted to identify serum samples with anti— body to LAV II from populations in the 0.5. at high risk for HIV infection. A total of 533 samples was tested using an EIA kit that included microwell strips prepared by Diagnostics Pasteur and components of the Genetic Systems LAV EIA. The samples included serum from 164 prostitutes in Miami, 181 Haitians in Belleglade, Florida, 164 gay men from San Francisco, and 24 seronegative people diagnosed as having AIDS. Eighty-two of the 533 samples were positive for antibody to LAV I and LAV II. These samples were confirmed as LAV I positive by Western blot. The EIA results therefore represent cross—reactivity between the two viruses. One hundred and eighty-seven samples were positive for antibody to LAV I alone; and none of the samples was positive for LAV II alone. The results of a research collaboration between the Food and Drug Administration, the Centers for Disease Control and Genetic Systems Corporation to study the epidemiology of LAV II in populations at high and low risk to develop HIV infection in the United States will also be presented. Rapid Progression of Infection of HIV Ab+ Transfusion Recipients from HIV-Infected Donors. THR53 JANE L. GARNER*, S.SAMSON*, K.CLAUSE*, J.HAWKINS*, J.WARD**, H. PERKINS*,et al., *Irwin Memorial Blood Bank, San Francisco, CA., **CDC, Atlanta, GA. We have followed 79 previous blood recipients of HIV—infected donors. Thirty—three were negative for anti—HIV and 46 were positive (Ab+). when first evaluated, 2 of the 46 Ab+ had ARC; none had AIDS. Six to eight months later, 10 had ARC (2 dead), 3 had AIDS (all dead). By the third visit, one more had ARC and two had died of AIDS. The total number of Ab+ recipients with disease was 14 (30%), 8 with ARC and 6 with AIDS. At the time of the initial visit, the frequency of abnormal laboratory results in recipients with (1) disease, (2) Ab+ but healthy, and (3) Ab— negative were as follows: Absolute lymphocytes <1 ISOOAMI: 57.1%, 34.4%, and 29%; helper/suppressor ratio <; 1.0: 85.7%, 78.1%, and 15.1%; and beta-2 microqlobulin:78.6%, 56.3%, and 26.7%. Antibody to hepatitis B and CMV did not differ between HIV Ab+ and Ab- recipients. The results demonstrate rapid progression of infection in this group of high-risk recipients. On the initial visit the likelihood of infection and subsequent disease both correlated with the frequency of abnormal results in three tests, but the differences were of only moderate prognostic value for the individual case. All tests became more frequently abnormal when signs of disease appeared, but we do not have enough serial samples yet on healthy Ab+ patients to see whether trends in values will be more useful prognostically. U2 THRs4 AIDS in Women in the United States A.M. HARDY, MARY E. GUINAN, Centers for Disease Control, Atlanta, GA Women make up only 7% of all reported AIDS patients, but are an under-recognized source for heterosexual HIV transmission as well as the source for transmission to infants. As of January 23, 1987, 1,993 women had been reported with AIDS in the United States. Their mean age was 35.1 years; 52% were black, 271 white, and 20% Hispanic. Pneumocystis carinii pneumonia (PCP), the most commonly reported disease, occurred in 66% of women, while Kaposi's sarcoma (KS) was reported in only 3%. Fifty-one percent of female patients were intravenous drug abusers (IVDA); 271 were heterosexual contacts of persons with AIDS or at high risk for AIDS (21% were U.S.-born women, while 6% were born in countries where heterosexual transmission plays a major role); 10% had received transfusion with blood or blood products; for 111, the means of transmission was undetermined. Compared with heterosexual male AIDS patients, women with AIDS were younger (p (0.01), but were similar by race, residence, and disease. When female patients were analyzed by year of report, the following significant trends (p<0.05) were noted: an increase in U.S.-born heterosexual contact cases from 14% in 1982 to 261 in 1986; an increase in mean age from 30.0 years in 1981 to 35.6 years in 1936; a decrease in the proportion of females in the IVDA group between 1983 and 1986 from 59% to 48%; a decrease in foreign-born heterosexual patients from 181 to 51. Increases in female AIDS patients in various risk groups were predictive of increases in pediatric patients whose mothers were in the some groups. The data indicate that heterosexual transmission of the AIDS virus to women is increasing. Continued monitoring of female AIDS cases will provide an indication of future trends in heterosexually-acquired and pediatric AIDS and information essential for prevention efforts. THP,55 HIV Exposure in New York City Streetwalkers (Prostitutes) ; Christonikos, N.; Mann, J, - Foundation lor Research on Sexually Transmitted Diseases; New York . New YOlk, U.S.A. Elghlycne street walking prostitutes were studied in |985. |986. and 1987 to determine the prevalence of HIV lnlection. Two health care workers and a driver Iound the women as Ihey worked Age, number at years working, and history of drug abuse were determlned. Consent was obtained and counselling was undenaken. Arms were examined for track marks while blood was drawn. Serum samples were screened (or HIV antibodies by ELISA and confirmed by Weslern blot, The ages ranged lrom I9 lo 37 ( mean 25. ) Time spent worklng as a prosfltule on the streets ranged Irom two weeks to 20 years (mean 5.4 years. ) Three 01 the subjects were men posing as women. One 01 them was also a drug user and was infected. or the 78 female subjects, twelve admitted to intravenous drug use and six (50%) were positive. 01 the 65 female prostitutes who denied dmg use live (7%) were positive. This could possibly represent heterosexual transmission. The overall seroposltivily rate was 1.1%, There was IIIIIe difference between 1985, 1986, or 1987. These Iiguves compare with 5% in Seattle, 25% in Miami, 6% in Athens and 88% in Rwanda. The incidence of this infection among New York City prostitutes does not seem to have increased greatly since I982 when the principal investigator conducted a study 01 T cell subsets in 33 proinIuIes. funded by New York State Deparlmem ol Heallh HIV anIibody IesIs penon-ned by the New York City Depanmem of Health Decreasing Survival in Recently Diagnosed AIDS—Related Kaposi’s Sarcoma: PAUL VOLBERDI.G, D.W. FEIGAL, K. EEARST, San Francisco General Hospital, San Francisco, THR56 CUTLER. CA. USA The survival of 162 consecutive AIDS/KS patients at San Francisco N. General Hospital was analyzed for variation related to the date of diagnosis. Patients were accrued between November 1980 and March 1984. 132 Patients are known to have died and 26 were surviving in January 1937. opportunistic infections 47 patients with prior or concurrent were excluded from analysis. Mean survival of quartiles of the cohort by diagnosis date were examined (Kaplan—Meier). Mean survival was longest in the early diagnosis group (1151 days) and prolonged in the subsequent quar— tiles (709,739,466 days respectively - p<.01). This worsening prognosis was even seen when patients with systemic signs (fev— ers, night sweats, weight Loss) were excluded. Adjusting for other prognostic variables (helper/suppressor ratio, ES? and hematocrit) with Cox regressions also did not eliminate temporal trends in survjval. KS treatment had no effect on .hese trends. Decreasing survival in AIDS/KS could have resulted from changes in diagnostic practices (delayed diagnos;s), increased viral virulence, changes in host resistance (eg. through changes in exposure to "cofactors" of immune deficiency) or in alterations in therapy. Adjustment of covaria’mes suggests that the worsen- ing prognosis of AIDS/KS is due to changes in :IIV virulence or in host cofactors. THURSDAY, JUNE 4 THR57 Recreational Drug Use Does Not Cause AIDS Progression, the UCSF AIDS Registry Cohort: AARON ROLAND, D.W. FEIGAL, D. ABRAHS. P.A. VOLBERDING. H. HOLLANDER, J. ZIEGLER, ILA. CONANT, University of California. San Francisco, CA, USA. A clinical cohort of 1396 patients at the out-patient AIDS clinics of the teaching hospitals at the University of California, San Francisco, have been recruited to participate in a registry with periodic follow-up. At entry. 511 of study participants have AIDS, 36% have ARC, and the remainder are at high risk. At baseline 67% of the cohort reports smoking and 881 report alcohol use. Recreational drug use was classified into three categories: Less than once/month More than once/year to once/year once/mouth Marijuana 601 181 221 Cocaine 831 132 41 IV Drug 952 21 3X Nitrite 83X 11% 61 Progression was defined as developing AIDS, CDC class lVCZ (ARC), lymphadenopathy syndrome or systemic symptoms characteristic of HIV infection. The relationship between recreational drug use and progression was examined with odds ratios comparing the lowest level of use to higher levels. 78 individuals were known to have progressed. No significant associations were found. Thus, although some types of substance use is associated with risk of seroconversion, once infected there is no evidence in this population that recreational drug use is a cofactor for progression. THR58 Severe HIV-Related lbrbidity and Mortality in Gases not Mating the (IX: Surveillance Definition for AIDS. DAVID L. (ll-IN, K.L. mm, LA. WY, F.N. JUNON, Denver Diem Control Service (Des), University of Colorado l-halth Sciences Center, Denver, 00, U.S.A. In 1981, the Centers for Disease (bntml (GE) developed a surveillance case definition (SD) for ABE, but it is now clear that the spectrun of disease associated with HIV infection is mich broader than the original SD. In order to provide a better animate of the true merit of severe mrhidity and mortality (SM) associated with HIV infection in Colorado, DCS investigated cases not metirg the SI) but which seemed likely to rmlt from HIV infection. Fran May, 1982 to September, 1986, there were 239 cases of (DC-definai AIDS reported to DCS. Durirg the same surveillance period, there were 33 cases of 914 reported and investigated. Five cases since have been diagmsed as (DC-defimd AIDS. Nine of the retaining 28 are livirg and still may develop ADS. The reasons for ecclusion by the SD were: 17 cases (612) the disease was mt considered indicative of cellular bunundeficiemy (CID); 7 (25%) a prior or concomi— tant iumnnsuppresive condition was present; am A (14%) the diagnosis was not reliably es- tablished. Diseasu not considered indimtive of CID included bacterial pneumis, bacterauia, Candida erdooarditis, Listeria mmingitis, tuberculosis, disseminated sporotrichosis, llodgldn’s lynphma, and ADE-demotia cmplex. Therefore, there are at least 19 and as mny as 28 cases of SM outside the S), representirg 8% to 121 of reported AIDS cases. This estimate does mt include cases of 8‘“ possibly missed due to mulerneportirg. We otmclutle that the OJC SD for AIDS significantly unierestimtu SM associated with HIV infection, that me: case of 914 are due to diseases not considered specifically indicative of CID, arri that the 01: case definition shmld be amandai. In the man, inclusion of such seam and other manifestations of HIV infection in surveillance registries will provide a better stimate of the true spectrun of illness associated with HIV, as well as useful information about tle natural history and prognosis of such patients. THPsg Analysing special features of a human lentivirus (HIV) infection ' and predicting the future development using computer based modeling (ASSP, AIDS Spread Simulation Program) Michael G Koch‘, Jose J Gonzalez“, Dietrich Dornar Etehr , Ulrich v Welc§:*'**, Magne Hyrtveit'un' Vac Karlsborg, Sweden, ‘53, Grim-tad, Norway, University Bamberg’. FRG, Robert Koch~Inst, Berlin, FRG, Munich, rec, ““ Inst 5 Informatics, University Bergen. Norway :”, Johanna L'age- m"Inst f Psychol, * .tiAcs’ The AIDS epidemic is a lentivirus infection, the unusually long and varying incubation period of which gives rise to several uncommon and insidious features in the epidemic's development, such as "transients“ and delayed effects which may cause severe biases. These are described. Indications are increasing for the possible role of macrophages as primary target cells for the HIV-infection, reason enough to consider the consequences of this hitherto underestimated virus survival in phagocytotic cells and what this would mean for the seroconversion latency. Many important conclusions follow from these assumptions. Different ways of forecasting are compared to each other with regard to their efficacy for various purposes. The methods of curve fitting (extrapolation), analogous calculation (interpolation), mathematical modelling (formalising), and computer-based structural models (simulation) are applied to various countries and to short and long term predictions. The development of a compartment-based computer program for simulating virus spread in large populations is described, the multinational modelling project ASS? (AIDS Spread Simulation Progran 173 “"350 EVIDENCE FOR A CODETERMINANT or AIDS ACQUIRED THROUGH RECEPTIVE ANAL INTERCOURSE ROGER DETELS, B VISSCHER, J GIORGI, H HO, .1 CHMIEL, I. KINGSLEV, ET AL. Hu tlcenter AIDS Cohort Study, NIAID, Bethesda, MD. A cohort of 537 homosexual HIV positive men in L.A. were followed for 18 months for changes in number of CD-4 cells. Seventy-one HIV antibody posi- tive men developed AIDS. The mean slope in (ID-4 cells was -.36/day (s.d.=.42) among men developing AIDS and —.01/day (s.d.=.01) among other seropositives. The mean slope by level of CD—A cells at baseline was: Subsequent AIDS Other Seroposltlves < 700 -.7.5 (s.d. = .15) .08 (s.d. = .20) 200—499 -.36 (s.d. = .38) .04 (s.d. = .26) > 500 -.46 (s.d. = .67) -.05 (s.d. = .33) The mean number of partners with whom cases practiced receptive anal intercourse the six months preceding baseline was 12.3 (s.d.=27.8) compared to 6.2 (s.d.=11.8) among other seroposltives. The greater negative slope of CD-4 cells and the more frequent receptive anal intercourse among cases suggests that receptive anal intercourse is a route of entry for a factor(s) which increases the risk of developing AIDS among HIV seropositive men. This observation agrees with lab data that activation of 00-4 cells promotes lytic infection with HIV. It is also possible that men frequently prac- ticing receptive anal intercourse were infected earlier and have progressed to AIDS by now. Follow-up of seroconverters to onset of AIDS should differ- entiate between these two alternate hypotheses. This observation provides a rationale for identifying agents acquired through receptive anal intercourse which stimulate a further decline in CD-4 cells and/or increase the risk of developing AIDS. By June data will be incorporated from an additional 1000 seropositive men in Baltimore. Chicago, and Pittsburgh. THP61 POSSIBLE Ell—FACTORS OF HUMAN IMMUNODEEICIENCV VIRUS (HIV) INFECTION I AMONG CENTRAL AFRICAN PATIENTS. P. HERMANS, F.K. LEE, M. PUNCIN, P. VAN de PERRE, A. NAHMIAS, N. CLUMECK. (St Pierre University Hospital, Brussels, Belgium, and Emory University, Atlanta, Georgia, USA). Parasitic and viral serology were performed among A45 central African people (CAP) (sex ratio: 1:1). There were A groups matched for age and sex: 94 CAP seen in Brussels with a clinical HIV infection (PBr), 148 CAP living in a Central African city (K)Y 121 healthy CAP living in Brussels (HBr) and 82 CAP from a rural equatorial area (R). HIV antibodies were detected by ELISA and Western blot techniques. Antibodies for Trypanosomia brucei (TB), Plasmodium falciparum (PF) and Entamoeba histolytica (EH) werescreened by immunofluores- cence. Herpes type I (HSVl) and type II (HSVZ) serology was performed by immu- nodut Enzyme Assay using monoclonal antibodies against HSVl and HSVZ purified glycoprotein. HIV seroprevalence among the various groups was: 99% (PBr), 19% (K), % (HBr) and 0% (R). Previous parasitic infection was more frequently found among rural (R) than urban (K) people (p (0.001 for all parasites) inde- pendly of their HIV serologic status. HSVl was commonly found in all groups (83 to 93%). HSVZ antibodies were found in 82% of HIV positive CAP compared with 38% of the negative patients (p (0.001). HIV and HSVZ prevalence was more marked among urban CAP (K) than rural people (respectively 1 % vs % for HIV: p< 0.001; 50% vs 30% for HSVZ: p (0.005). Among CAP living in BrusselsY HSVZ seropositivity was strongly correlated with HIV seropositivity (p<:0.001). HSVZ seropositivity was similar (A % vs 29%) among HIV negative urban or rural people. This study shows that HSVZ seropositivity is strongly associated with HIV infection in Central Africa. Herpes type 11 could be a co—factor of HIV infec— tion among promiscuous heterosexual Africans. THR62 Epidemiologic observations and predictive factors for AIDS in a cohort of New York Homosexuals: 5 year follow-up. M. LANCE, E.B. MEIN. Y. INADA, G. MoKINLEY. W. RAMEY, M.H. GRIECO, St. Luke's/Roosevelt Hospital Ctr, Columbia University, New York, N.Y. USA. 104 Hamsexml Volunteers (H/S) have been followed at 6 month intervals for 5 years. Of 56 volunteers seropositive for the human inmunodeflciency virus (HIV-pas) at entry into the study, 24 (42.8%) developed AIDS (1 in ’82, 4 in '83, 8 In '84, 6 in '85, 5 in '86) and 8 developed ARC (14.3%). 0f 48 HIV seronegative (HIV—neg) volunteers, 5 serconverted to an HIV—pas state but have remained asymptomatic. Cytomegalovirus (CMV), Enlerovlruses (EV) were cultur- ed with hlgh but approximate equal frequency from both HIV-Pas and HIV-Neg volunteers from one or more of five sites (Blood, Semen, Urine, Throat, Rec- tum). of multiple laboratory parameters performed prospectively at 6 month intervals, the combined appearance of acid—labile interferon Alpha (AL-IFN), disappearance of the Erythrocyte receptor for complement 38 (E-CRI) and app- earance of a triple positive coombs test (positive for IgG, lgM, complement 38) in an HIV-Pas individual invariably heralded progression towards overt AIDS within 6 to 27 months. This combination of parameters was not‘found in HIV—neg individuals including those with CMV-viremla. Our owervutions suggest 1. Culture-positive CMV infection is frequent in N.Y.H.S. and is unrelated to the HIV infectious status. 2. The appearance of AL-IHV, triple positive direct Coombs'lest and absence of E—CR1 in llIV—pos subjects reflects active pathogenic processes directly related to the progres- sion towards AIDS that are not dependent on the reactivation of CMV. THURSDAY, JUNE 4 THP63 HIV Antibody Prevalence in Pregnant Haitian Women ' NEAL A. HALSEY, R. BOULOS, J.R. BRUTUS, T. QUINN, E. HOLT, C. BOULOS, Johns Hopkins University School of Hygiene and Public Health and School of Medicine, Baltimore, MD, Tulane University School of Public Health and Tropical Medicine, New Orleans, LA and Port-au-Prince, Haiti. Pregnant women residing in an impoverished urban slum were screened for antibodies to HIV. Of 1240 women tested in 1986 by ELISA, 114 (9.2%) were positive and 104 (91%) were confirmed by Western blot with antibody to both env. and gag. proteins for an 8.4% confirmed antibody prevalence rate. Four additional ELISA positive specimens contained antibody to env. or gag. only and were considered indeterminant. The prevalence rates of antibody in the 55% of married women was 11.5% versus 4.5% to 7.6% in women with less formal bonding to men. The prevalence rates by age groups were: Age in Years Age in Years Age in Years 15 — 19 7.5% 25 - 29 8.6% 35 - 39 8.9%. 20 - 24 11.2% 30 - 34 6.5% The 8.4% prevalence rate of MB confirmed antibody to HIV in 1986 was only slightly higher than the 7.6% rate observed in a sample of 533 mothers of young infants bled in 1982. Aliquots of sera tested in 1982 were retested with second generation ELISA and NB assays and found to give virtually identical results. Thus, the rate of increase in HIV antibody prevalence in this population does not appear to be as rapid as reported in other high risk populations in Africa or in the U.S. THR64 Incidence of AIDS Related Clinical Manifestations in a Large Cohort of Gay/Bisexual Men RICHARD A. KASLOW, W.C.BLACKWELDER, J.P.PHAIR, D.I..YTER, R.FOX, B.VISSCHER for the MULTICENTER AIDS COHORT STUDY(MACS), NIH, Bethesda, MD, USA _ Few studies have documented the incidence of new AIDS related clinical manifestations. We analyzed these clinical features in a prospective study of gay/bisexual men examined semiannually. Combinations of symptoms, physical signs, and lab abnormalities that correlated best with a low CD4 count or eventual AIDS were used as an index of clinical involvement. Within 18 months of follow up, at least 231 HIV+ men newly developed substantial clinical involvement (a high clinical index score). Life table probabilities of reaching this threshold score are shown for men who were HIV+ (Initial N=1809) and men who were HIV- (Initial N=2864) throughout the interval. 2 with substantial AIDS related clinical involvement At Newly reached in: Cumulative entry lst 6 mo 2nd 6 mo 3rd 6 mo Z HIV(-) 1.3 0.7 0.9 1.1 2.7 HIV(+) 5.3 4.1 6.0 8.1 17.2 (+). Entry CD4=700+ 3.2 2.4 1.9 6.7 10.8 (+), 400-699 3.7 2.7 6.5 7.4 16.1 (+), 0-399 11.9 7.8 14.1 14.4 32.3 The 18 month cumulative incidence of substantial clinical involvement in seropositives was 17.22 and varied with initial CD4 count from 10.81 to 32.32. The data also suggest that the probability of reaching a high clinical index score in a 6 month period was not constant but rose with time regardless of initial CD4 count. It is not yet clear whether this steadily increasing incidence of AIDS related manifestations correlates with the likelihood and rate of progression to AIDS. THP65 MW Sera to Human Immunodeficiency virus (HIV) and Simian T-Lymphotropic Virus DI (STLV-III). JULIUS AIA. MINGLEL, M. HAYAW“, M. OSEI-KWASI**, Y. ISH]:KAWA***,A. R. NEEQUAYE“, V.NETTEY***, et.sl. *University of Ghana Medical School, Accra, *‘Noguchi Memorial Institute for Medical Research, Legon, Accra, "*Institute of Medical Science, University of Tokyo, ****St. Joseph Hospital, Koforidua, Ghana. Acquired immunodeficiency syndrome (AIDS) in Africa which was previously confi- ned to the East and Central African countries is now in West Africa. The. disease in Africa may take an epidemic character if measures are not taken to check its spread. Prevalence rates and the risk groups therefore need to be assessed and identified. Detection of antibodies (Abs.) to HIV and STLV-III antigens (Ags.) was carried out in human sera from blood donors, prostitutes, sickle cell disease patie- nts and others. The ELISA and Immunofluorescence (IF) techniques were used for HIV Ags. and IF for STLV-III. out of a total of 997 samples (226 from prostitutes) examined for HIV and 737 for STLV—III. Abs. 93 including 57 prostitutes were positive for HIV and 18 for STLV- 111. Abs. Some of the sera reacted better to STLV-IlI Age. Western blotting test al- so confirmed these differences. Reports on Senegalese showed that some reacted to STLV-III Ags.without any di- sease. The Ghanaians reacting to STLV-III showed disease. The Western blotting reaction suggests that some of the Ghanaians have been exposed to a virus which may be closely related to STLV-IlL A new virus HTLV—IV has been reported from Senegal. Retrovirus infection in Africa may therefore be more varied than in the Western Hemisphere. Isolation and characterization of local strains of HIV and their inclusion in tests as Ags. may be necessary to determine the incidence rates in some of these African countries. Work is currently going on in this direction. 174 THP66 Epidemiologic Characteristics of women with AIDS in New York city ' EAR! Am! CHIASSON, E. FLEISHER, D. PETRUS, B. MILLER, New York city Department of Health, NY, NY. The annual. death rate due to AIDS per 100,000 women 25—4A years of age in New York City (NYC) has increased from 0.4 in 1981 to 15 in 1986 (based on the AIDS case registry). In order to identify women most at risk for infection, the characteristics of women with AIDS in NYC were determined through an analysis of surveillance data. The 867 female cases in NYC represent 101. of all NYC cases and 451. of all female cases reported nationally. In 1986 the incidence of AIDS per 100,000 women 25—44 years of age in NYC was 48 for blacks, 8.5 for whites, and 36 for Hispanics. The major risk behavior reported was IV drug use (IVDU) by the women (611.) or their sex partners (181.). In addition, 31. were sex partners of other at risk individuals, 4.51. were from countries where risks are unclear, 3.51. were recipients of blood or blood products, 2.5". had no identified risk factor(NIR), 2.51. were lost to follow—up, and 51. were under investigation. The average age of the IVDUs, the sex partners of at risk individuals, and women from countries where risks are unclear was 33, while that of transfusion recipients was 50, and that of the NIRs was 38. In NYC, 511. of the female IVDUs with AIDS are black, 151. are white, and 341. are Hispanic. Among the female sex partners of at risk individuals, 411- are black, 161. are white, and 431. are Hispanic. 0f the female transfusion cases, 25% are black, 681. are white, and 71. are Hispanic. In 1985 AIDS was the leading cause of death amng women 25 to 29 years of age in NYC. These data show that in NYC AIDS is a leading cause of morbidity and mortality mug women 25—“ years of age and that women Mac are IVDUs or sex partners of IVDUs are at greatest risk of infection with HIV. THP67 Evidence for a Causal Association Between HIV Infection and I Increasing 'mberculosis Incidence in New York City. RAID 1.. STOHEBURHBR". 1). Des Jeri-is“, J. Hilberg*, 5.x. Priedman’fl", J.L.Sotheran***. The New York city Depart. of Health‘. The I.Y.s. Div. Substance Abuse Svcs.**, and Narcotic and Drug Research Inc)“, NY. IY. Concurrent with the AIDS epidemic, New York City tuberculosis (1's) incidence rates have increased 60%, from 20/100,000 in 1900 to 32/100,000 in 1986. The groups with the largest increase in incidence have been males aged 25—44 who are black (from 96 to 231 cases per 100,000) and Hispanic (from 35 to 103 cases per 100,000). These groups also account for 521. of all “C AIDS cases aged 25—“. In order to investigate the association between HIV infection and TB. two studies were undertaken: we matched the NYC TB and AIDS surveillance registries to determine TB incidence mug AIDS cases; and we used the TB registry to determine TB incidence in 519 intravenous drug users (IVDU) enrolled in a study of risk factors for HIV infection and AIDS. Of 6,365 AIDS cases diagnosed from 1982 through April. 1986, 266 (6.21.) also matched with the TB registry. Compared to AIDS cases with the lowest risk for TB (whites and gay men). groups at high risk for I'D were blacks (on 4.5.951. CI-3.2—6.2), Hispanics (OR 2.9 951 cl:2.0—4.3), and IVDU (OR 3.6 95% c1=2.1—4.8). Among the 519 “DU, 12 cases of TB were identified and all occured mug 279 persons with serologicsl evidence of HIV infection or clinical AIDS (p<.001). These data support the hypotheses that persons co—infected with TB and HIV are at a higher risk of TB disease than similar persons without HIV infection. and that AIDS and HIV infection are causally related to increasing TB incidence in IYc. Areas with populations that have a high prevalence of TB and HIV infection should anticipate similar increasing TB trends and plan prevention and control strategies accordingly. of THPSB Genital Ulceratian As I Risk Factor For Human ' Immunodeficiency Virus Infection In Kenya RUTH H. GREENBL TTD, SL. LUKEHART’, FA. PLUHHER'D, TC. QUINN»... CH. CRITCHLDHI, LJ. D'COSTA-HH, et al., DUniver-ity of Washington, Seattle, Washington, USA; DIUniveraity of Manitoba, Winnipeg, Hanitoba, Canadagnu Johns Hopkins University, Baltimore and the National Institute of Allergy and Infectious Diseases, Bethe-Ida, Haryland, USA; acneflairobi City Council Sexually Transmitted Dimes-ea Clinic, Nairobi, Kenya. We studied 115 heterosexual men with genital ulcer: in I sexually transmitted diseases clinic in Nairobi, Kenya and found the prevalence of serum antibody to human immunodeficiency viru- (HIV) in this population was 16.5% which is higher than the prevalence reported in other groups of men in Kenya. Our results also indicate that genital ulcer disease may increase risk of infection with HIV. Of 19 men with antibody to HIV, 12 (63.2%) reported previou- genital ulcerl, versus 30 (31.3%) of the 96 man without antibody to HIV (p=.008). Logistic regression analysis chewed that antibody was significantly associated with a past history of genital ulcers (p=.03, odds ratio 3.71, 95% confidence limit. =l.1d- 11.42) but not current or previous episodes of other nexunlly transmitted diseases, or the etiology of current genital ulcers. Genital ulcers are a common sexually transmitted disease in Africa and may contribute to the increased risk for HIV apparent among heterosexual. in this region. THURSDAY, JUNE 4 1'”ng Cohort stgdy of New York City male hgmosexuals, 1981-8 . * H. MA R , NN U - AC T , S. ZOLLA-PAZNER , N. EL- SADR , P. THOMAS , T.J. SPIQA , et al., New York University Medical Centg;* New York, NY, USA, New York City Department of Health, New York, NY, Centers for Disease Control, Atlanta, GA, USA. Eighty-six male homosexuals who participated as controls in case-control studies of AIDS have been followed prospectively. Minimum cumulative HIV infection was 30% (21/69) in 1981—2, 39% in 1982-3 (31/79), 48% (41/85) in 1984, 48% (41/86)in 1985, and 51% (44/86) in 1986. Seven cases of AIDS have occurred. The longest follow-up of AIDS-free, HIV-infected subjects was for 8 persons who were seropositive in 1981-2. The median 0KT4/0KT ratio of these 8 in 1986 was 0.36 (mean 0KT4 cells-421, SDsI78 cells/mm ); 7 of the 8 have shown continual declines in 0KT4/0KT8 ratios. Another 8 AIDS—free subjects have seroconverted. In the combined group of 8 subjects who were seropositive on enlistment and 8 seroconverters mean 0KT4 cell counts de- clined with duration of follow-up. Interviews revealed that 12/65 (18%) subjects had been celibate in the 6 months prior to interview in 1986 and an additional 3 (5%) had adopted strict "safe sex" guidelines including 100% use of condoms during anal intercourse. Although the cohort as a whole showed a decline in the number of sexual partners between 1985 and 1986, subjects who eliminated all risk of sexually-transmitted AIDS were significantly more likely to be seronegative than those who continued to place themselves or others at risk. These data suggest (a) that duration of infection is associated with severity of AIDS-related immunologic abnormalities, and (b) that educational efforts to reduce HIV transmission among homosexual men have not strongly affected those who have been so ac- tive sexually as to have become HIV infected. THR70 AIDS in New York State Prisgn Inmates e . * kDALE L. HORSE , J. HANRAHAN , B. TRUMAN , J. FECK , M. HOELFEL , 5; BROADDUS , et al., New York State Department of Health, Albany, NY, New York State Department of Corrections, Albany, NY, USA. Through January 15, 1987, 3A7 cases of AIDS had been reported among prison inmates in New York State correctional facilities. This represents approx- imately half of the inmate AIDS cases in U.S. state and federal systems. An analysis of epidemiologic data on these cases has shown an increase in cases yearly from 2 in 1981 to 107 in 1986, with an incidence of 302 cases per 100,000 inmates per year over the past 2 years. Case ages ranged from 18 to 59 years: 335 (971) were male, 12 (3%) were female. Forty-six percent were hispanic, 391 black and 141 white. Pneumocystis carinii pneumonia (76%) and other opportunistic infections (17!) were the most common diagnoses, while Kaposi's sarcoma was rare (3%). To date, 228 have died and AIDS has become the leading cause of death among inmates causing > 501 of deaths. IV drug use (971) was the major risk factor and most inmates had lived in the NYC area prior to incarceration. Only 12! gave a history of homo- /bisexuality and 801 of these used IV drugs. A comparison of 52 cases with 101 matched controls, showed that inmates who developed AIDS had sig- nificantly (p >.01) lower entrance HDC counts, hematocrit, and albumin, and higher globulin and SGOT values. Logistic regression analysis of the 52 cases and 196 random controls showed previous IV drug use, low HBC count, elevated serum SGOT and globulin, and race to be risk factors for develop- ment of AIDS. No long term inmates (27 years of continuous state incar- ceration or admission prior to, 1978) have developed AIDS, but a more definitive study on risk of transmission during incarceration is needed. THB71 Evaluation of HIV IgM and Antigen Assays for Determination of Perinatal Infection with HIV. SHELDON LANDESMAN*, H. MENDEZ", B. BIGGER”, C. LANE", A. WITTEK‘I", S. ALEXANDER"**, J. GOEDERT**, et al. SUNY Health Science Center at Brooklyn", NIH“, FDA***, Biotech“**, Washington, D.C. No serologic assays are available to distinguish HIV infection during infancy from passive maternal antibodies against HIV. Coded sera from 14 third-trimester pregnant women and serial specimens from their offspring (up to 3—9 mo. of age) were tested blindly for HIV—p24 antigen (HIV-Ag), for anti—HIV IgG and IgM by whole virus Western Blot (NE) and by ELISA using recombinant env and gag proteins. By conventional whole virus ELISA and NB, 8 mother-infant sets were positive and 6 sets negative. There was serologic evidence of infection in two sick babies; one with HIV-Ag env—IgM(6 months), env-IgG and gag-IgG; the other had no HIV—Ag but transient gag-IgM (age 1 mo) and env-IgM (ages 1-2 mo) with a subsequent increase in gag-IgG and env-IgG (ages 2—6 mo). A third baby had no HIV-Ag or IgM by ELISA, but at ages 2—6 mo did have a modest increase in gag-IgG, env—IgG, WB-IqG (p17 p24 p55). The remaining 5 infants of seropositive mothers had no HIV-Ag, no IgM by ELISA, and declining IgG by ELISA and WE: one of them is symptomatic. All 14 babies had faint WB-IgM bands especially at p24. Two seronegative mothers had env-IgM and gag-IgM without HIV-Ag, IgG, subsequent seroconverison (after 3-6 mo) or evidence of HIV in their babies. These data suggest either that relatively few (perhaps 2/8) babies of HIV-seropositive mothers are infected or that HIV assays for IgM and Ag require improved sensitivity and specificity to distinguish HIV infected babies during the first 6 months of life. 175 THE-’2 Heterosexual Transmission of AIDS in Canada - National Surveillance KIMBERLY D. ELMSLIE, Alastair J. Clayton, Laboratory Centre for Disease Control Department of National Health and Welfare, Ottawa, Ontario, Canada. Between February 1982 and January l987, 843 adult AIDS cases were reported to the national surveillance program in Canada. Risk factor data indicate that al- though homosexual men have accounted for an increasing proportion of the total reported cases, heterosexual AIDS cases were observed very early in the course of the epidemic, and have been reported consistently over time. In 3.6 percent of all AIDS cases reported, heterosexual activity was considered the probable risk factor for HIV infection. Nine cases were white males aged 35-57 years (median 45 years); ll were white females aged 24-58 years (median 40 years);and l0 were Haitian females aged 25-32 years (median 29 years), who had emigrated to Canada prior to l980. Six of the males reported sexual activity with female prostitutes, two had multiple female sex partners, and one had a sex partner who developed AIDS. The female cases were attributed to sexual activity with individuals who later developed AIDS or whose lifestyle included activities known to increase the risk of exposure to HIV. The first AIDS case in Canada attributed to heterosexual activity was diag- nosed in 198l. In each of the five subsequent years to the end of 1986, 2 per- cent to 4 percent of AIDS cases reported this risk factor. These surveillance data indicate that heterosexual transmission is not a new phenomenon in this country and this mode of transmission has accounted for a small but consistent proportion of AIDS cases diagnosed each year. Bidirectional sexual transmission of the infection is supported by the sex distribution observed among these cases. The cases were reported fromthe large urban centres where HIV infection is most prevalent. THR73 Cohort Study of HIV-seronegative Homosexual Men: Predictors of Seroconversion and Clinical Course of Early HIV Infiction ANN c.co;LIER , V.L.Murp yl, P.L.Robertsl, H.H.Handsfieldl'2 Univergity of Washington and Seattle-King Co. Dept. of Public Health , Seattle WA, USA. Most data on factors associated with HIV infection in homo— sexual men(HM) are based on case control studies comparing HIV— seropositive(HIV+) with HIV-seronegative(HIv-) men. We have followed a cohort of HIV-HM and prospectively examined factors associated with HIV seroconversion. Among 92 HM without clinical problems suggestive of HIV infection examined in 1982-85, 25(27%) were HIV+. of 67 HIV-HM, 45(67%) were followed for 18-47 mo(med—ian 39 mo). Among these, 14(33%) became HIV+ after 2—44 mo(median 21 mo). Compared with the 29 persistently HIV-HM, the 14 ser-oconverters had more sex partners in the interim before serocon-version(median 6 vs 2 partners,P=o.017); more commonly had a new partner in the preceding 1 mo(ll/13 vs 11/28,P=0.009): and more commonly participated in receptive anal intercourse with rectal ejaculation(10/11 vs 13/28,P=0.012). There was no difference in overall secretion exchange during sex(11/12 vs 23/29, P=NS). Nine seroconverters developed generalized lymphadenopathy(GL)(detected when first HIV+ in 6, and 3—24 no later in 3). GL persisted >3 mo in 8. These results support the hypothesis that receptive anal intercourse and increased numbers of sexual partners are specific risk factors for acquisition of HIV in HM, and suggest that most recent HIV infections are associated with clinical findings. THPJ4 Statistical analysis of Mopean AIDS surveillance data: trends and predictions. AREA 11. ME‘, R.A. m, J.C. Jam“, J—B. W. “Collaborating Centre on ADS, Paris, France, “National Institute for Public Health and mvirotmtal Hygiene, Bilthoven, Netherlands. Duxxcan AIDS surveillance data have been analysed statistically to assess incidence trout and to provide short-term predictions. After adjustment for estimated reporting delays, the data (cases per half-year of diagnosis) me fitted to an exponential model. For the Duopean Calamity (E.C.) as a whole (90% of Hiropean cases reported) and for 10 individual countries (those with at least 50 reported cases by 30 dime 1986), the temporal evolution of the epidenic was assessed by performing regressicn analysis over a succession of time intervals (window). For 3 countries, separate analyses have also bee) carried out for the two main risk groups (hm/bi—samal men: IV drug abusers) . Predictions to mid-1988 have been made by extrapolation based on estimated current dwbling tins. Available results are based on data reported as of 30 June 1986. Reportim delays were found to show considerable between-«xmtry variation. For the D.C. overall and for most individual countries (with the exception of Italy, Spain and Switzerland), dmblzing times were found to be increasing with time (for the E.C., from 6.5 mnths to 9.4 mantis over 2.5 years), as observed in the U.S.A. Preliminary analyses by risk group straigly suggest that the different evolutim in Italy and Spain may be related to the much larger proportion of cases allmg IV drug abusers in time countries, but this result is not yet statistically significant. ktimatas of current doubling times range from 4.3 naiths (Italy) to 17.7 moths (Delmark) . If the dwhlim time for the D.C. as a whole were to remain at its curraitly estimated value of 9.4 over the next two years, the mmulated total of cam diagnosed in the D.C. could reach around 19,000 by mid-1988. Hopefully, this shmld represent an overestimate as doubling times are likely to omtime to increase. Results will be up-dated to include all cases reported as of 31 Decsnber 1986. THURSDAY, JUNE 4 THR75 Seroepidemiological Study of HIVl and HIV2 Infection in Guinea— Conakry Christine KATLAMA”, M. HARZIC*, K. KOUROUMA**, M.C. DAZZA*, F. BRUN-VEZINET*‘ *Hdpital Claude-Bernard, Paris, France,‘*Comité SIDA, Ministers de la Santé, Guinée—Conakry LAV2/HIV2 is a human retrovirus recently described in patients from Western Africa. To evaluate the presence of HIV infection in Guinea—Conakry, sera were collected, in october 1986, from 914 subjects (518 males, 396 females) in two areas - Conakry, the capital (756 subjects) and Labbe, a city of the north-east country (158 subjects). Sera were tested for antibodies to HIVl (HIVl-Ab) and HIV2 (HIV2—Ab) by Elisa (Diagnostics Pasteur) and confirmed by Western blot(WB) In Conakry, HIV seropositivity was found in 8/756 subjects : 2/81 were patients hospitalized in medicine ward, 5/121 patients with tuberculosis and 1/277 was hospital health—care worker; 6 were HIVl—Ab 0 and 2 HIV2-Ab 0. No HIV-Ab were found neither in 167 females attending gynecology/obstetrical clinics nor in 110 military recruits. In Labbe, 1 hospitalized patient had HIVl—Ab 0 while 127 subjects from general population were HIV seronegative. This study shows a prevalence of HIV infection of — 1% (9/914) in this tested population; the highest rate was found in tuberculosis patients (4/121). Besides.4 sera were repeatedely HIVl—Ab 0 by Elisa; when analysed by WB. they exhibited only antibodies to gag (p18—p25—p40—p56) and pol (pad-p38) gene products with no Ab to the envelope glycoproteins of HIVl (gp160.110.41) or HIV2 (gp130.105). Presence in Guinea of both HIV1 and HIV2 is evidenced by this study; a low prevalence of HIV infection in countries as Guinea is an argument to undertake rapidly management for prevention of transmission, such as blood— bank screening, before the extent of retroviral infection. We thank C.E. DE TSERCLAES for assistance. THP76 Predictives of AIDS in a clinical cohort of HIV infected patients. ' VICTOR DE GRUTTOLA*, J. LIVARTOWSKI**, W. ROZENBAUM“*, P.SETTE**, B. AUTRAN**, F. DE VATHAIRE**‘. “HARVARD MEDICAL SCHOOL USA, *“PITIE SALPETRI- ERE HOSPITAL, ***GUSTAVE ROUSSY INSTITUTE PARIS FRANCE. Since 1983, over 500 patients with confirmed HIV infection, without AIDS, have been followed. Of these patients, 22 developed clinical AIDS in follow—up of 1 to 3 years. Of these, I“ had ARC at their examination 6 had lymphadenopathy, and 2 were asymptomatic. To determine the power of a variety of laboratory tests to predict the development of AIDS, a matched case-control study was performed. Each patient who developed AIDS in the course of follow—up was matched with a control who had the same initial clinical findings at that time. These data were analyzed using matched logistic regres- sion analysis. The variables analysed were the numbers of white blood cells, lymphocytes, TA and T8 cells, the levels of serum B2 microglobuline IgG and IgA level. The most important predictor for the development of AIDS was the absolute number of T—helper cells(Tu) followed by the level of betaZ—microglobu line(BZ). From univariate analysis, the crude odds ratios for the development of AIDS were .08 for T4 > “00 vs. T” <400(p=.02) and .18 for B2 4 350 vs BZ > 350 (p=.09). When both variables were entered simultaneously in the logistic model, the regression coefficients were not much changed although the signifi- cance levels associated with them were higher. Thus, level of betaZ-microglobu- line appears to provide more information than does T—helper count alone concer— ning the risk of developing AIDS, but larger sample sizes will be needed to confirm this hypothesis. Linear regression analysis demonstrated that the most important predictor of the level of T“ cells 6 months after the initial clinical visit was the level of T4 at the initial visit but the level of 82 microglobuline also had a predictive value. but initially Is HIV Infection Increasing in the United States? A Review of THE-l7 Evidence from Sentinel Populations TIMOTHY J. DONDERO", J.R. Hanson)“, J. BIch-IER”, my. mnn***, J.D. SCHORR AIDS Program, CID, Centers for Disease Control, Atlanta, GA, MDepartment of Defense, Washington, D.C., ***Amarican Red Cross, Washing— ton, D.C. It is widely assumed, though without evidence, that human immunodeficiency virus (HIV) infection is increasing in the United States, since reported AIDS cases continue to increase. We reviewed divergent infection trend information from two large volunteer groups: military recruit applicants and American Red Cross blood donors. To date, approximately 900,000 recruits and 7,000,000 donors have been tested for HIV antibody by ELISA and, when reactive, confirmed by Western blot. Overall, 1.5 of every 1,000 recruits tested were positive (1.2/1,000 when sex adjusted). Infection rates vary by age (17-20 yrs., 0.6/1,000; 21-25 yrs., 2.5/1000; Z 26 yrs., A.1/1,000), sex (males, 1.7/1.000; females, 0.7/l,000), race/ethnicity (whites, 0.8/1,000; blacks, A.1/1,000; Hispanics, 2.1/l,000), and geographic area. However, during the observation period, the level of infection did not significantly change either in the aggregate or by demographic or geographic subgroup. Blood donors averaged 0.23 per 1,000 tested, varying by sex (males, 0.29/1,000; females, 0.07/1,000) and geographic area. Detection rates decreased from the initial 0.38/1,000 level, due to the elimination of previous positives among repeat donors. However, preliminary analyses of first-time donors suggest that rates in that group doubled over a l-yesr period. Reasons for the apparent divergence between recruit and new donor trends are unclear. The groups differ in socioeconomic, geographic, and age composition; degree of exclusion of persons with exposure risks; and likelihood that some participated specifically to determine their HIV— antibody status. Evaluation of these trends by a monitoring system indepen- dent of self-selection bias, such as the sentinel hospital based sur— veillance, is essential. U6 THR78 B. BUTTIGER, I. BERGGREN, J. LEITE DA COSTA, M. MARLENE, L. LUZIA, G.BIBERFELD. National Bacteriological Laboratory and Danderyds hospital, Stockholm, Sweden. Ministry of Health and the National Blood Bank, Luanda, Angola. A seroepidemiological study of HIV and HTLV-IV infection was performed in the capital Luanda and in the Cabinda district, which is situated as an enclave be- tween Kongo and Zaire, in Angola in October 1986. Until October 1936 five cases of AIDS had been registered in Angola. During this study another three cases with clinical AIDS, as defined by the Bangui criteria, were found and confirmed by HIV-serology. Sera from groups of healthy persons and groups of patients were screened for HIV-antibodies by ELISA(Drganon-Teknika) and for HTLV IV-anti bodies by immunofluorescence on HTLV IV—infected HUI-7B cells or by dot immuno- binding. All screening positive sera were tested by Western blotting with HIV- and/or HTLV IV—antigens. In Luanda HIV-antibodies were demonstrated in 2/452 (0.4%) male blood donors, in 1/357 (0.3%) pregnant women, in 1/100 ( %) pati- ents hospitalized with tuberculosis, in 4/94 (A%) patients at medicine wards and in 0/22 women hospitalized with pelvic infections. Two known male AIDS- patients and two of their three wifes were also HIV-seropositive. In Cabinda 4/38 (11%) women at a maternity ward were found HIV-seropositive, but only 1/52 (2%) of other hospitalized patients and none of 31 male blood donors or 59 heel thy persons in a village on the border of Zaire. Specific antifiwiies to HTLV IV were not found in any of 177 blood donors or 100 patients from Luanda. However, eight out of nine HIV positive sera crossreacted with HTLV IV by immunofluore- scence and with HTLV IV gag proteins by Western blotting. HIV infection exists in Angola, but not to the same high extent as in some neighbouring countries in Central Africa. Prevalence of HIV- and HTLV IV-infections in Angola. THE79 Differential Participation Rates and Epidemiologic Estimates of AIDS. LAURA DEAN, J.L. MARTIN, Columbia U.,School of Public Health, N.Y.C. Studies on AIDS among gay men and IV drug users show a high degree of vari- ability in prevalence rates of HIV infection, ARC and AIDS, and it is clear that a significant amount of this variation is due to methodological biases, including recruitment procedures and attrition rates. This presentation begins to address this problem by describing the relationship between differential rates of participation and attrition and ethnic and sexual behavior factors in a gay male NYC cohort of 745 men recruited for a longitudinal AIDS study in 1985. This group was selected from diverse community channels with special efforts made to recruit black and Hispanic men. Even with these efforts black and Hispanics made up only 13% of the sample. Surveillance data at that time indicated that 33% of gay/bisexual AIDS cases in NYC were minority group members. This initial bias was compounded by differential attrition rates of whites and non-whites at one year follow-up. The overall attrition rate was 11%. However, black and Hispanic men were more than three times as likely to be lost to follow—up (25%) as were white men (8%) due to more often refusing to be reinterviewed, posing insolvable logistics problems and being ill or dead due to AIDS. This difference is problematic because men who declined to be reinterviewed reported having more than twice as many sex partners in the year before they learned about AIDS (mean=2Al) than did men who were inter- viewed at both times (mean=108). These men were also more than five times less likely to have enrolled in the HIV antibody evaluation component of the study compared to those who were reinterviewed (9% vs 50% respectively). ‘These results suggest that the highest risk individuals, the highest rates of HIV infection, and the highest rates of AIDS are to be found in the subset of individuals who never enroll or are unwilling to continue participation in behavioral and serologic AIDS studies. THEBO IV Drug Abusers with Homosexual Activity: of Subtypes of Men with Two Risk Factors Ronald Stall*, W. Wiebel**, Ostrow ***, *Rutgers University, New Brunswick, NJ, **University of Illinois, Chicago, IL, ***University of Michigan, Ann Arbor,MI. Men who are IV drug abusers (IVDA) and have male sexual partners are of spec— ial interest in texns of the epidendology and prevention of HIV transmission since they are at high risk of exposure through two independent nechanisms and may serve as a link to heterosexual transmission. A nethodologically rigorous estimation of the absolute numbers, social characteristics, and behaviors of such men is difficult to obtain. We will present information obtained from several ethnographic studies which support the existence of at least 2 sub- groups of such non: 1. Men with primary identification with the IVDA subculture: Such men share the general characteristics of inner city IVDAs, including lower SES, chronic use of drugs such as heroin, regular sexual contact but a low level of social identity with the gay subculture, homosexual contacts are highly stigmatized and often are furtive and include the exchange of money, poorly informed about the sexual transmission of HIV and are unlikely to be reached through research and educational outreach to the gay connmnity. 2. Men with primary identification with the gay subculture: Such men are relatively rare and tend to be older and of higher SES than the first group of nen. They are relatively well inforned about the sexual transmission of HIV but may be uninforned about the risks of needle sharing. Their IVDA tends to be of an episodic and recreational nature, often associated with sexual activi- ties or gay social settings. Drugs used IV tend to be cocaine, anphetanines and MDA rather than heroin and they tend to View nessages aimed at IVDAs as irrelevant. Designing interventions ained at these two subgroups appears warranted. An Ethnographic Study THURSDAY, JUNE 4 TH281 AIDS Surveillance in Europe R.A. ANCELLE, J-B. BRUNET, A.M. DOWNS, WHO Collaboraté ing Centre on AIDS, Paris, France. A WHO Collaborating Centre on AIDS was set up in April 1984 at Claude Bernard Hospital in Paris (France) in order to collect epidemiological information from the AIDS surveillance systems in European countries. The Centre uses the CDC case definition; the data are provided by one source per country which is recognized by the respective national health authorities, and quarterly reports of the situation are published. By December 1986, 27 countries were reporting to the Centre. Although France reports the greatest number of cases (1350), the rates per million popu— lation are higher in Switzerland and Denmark (29.5 and 25.7). The trends of these rates show that most countries are now facing an epidemic. Overall, the majority of cases have been diagnosed among homosexuals (69%) but a steady increase is noted in the IVDA group (14%). There are geographic variations between the northern countries (predominance of homosexuals) and southern countries (predominance of IVDA). The majority of the paediatric cases are children whose mothers belong to one of the groups highly represented in the country of diagnosis. This network enables comparative views on specific problems (e.g. public health), initiation of collaborative studies, and information exchange for ongoing studies in the European region. An update of the situation by March 1987 will be presented. THEBZ Risk of Heterosexual and perinatal transmission of Human Immunodeficiency Virus Infection (HIV) Among Spouses and Children of Hemophilic Patients with AIDS Hugh C. Kim. K.Raska. Jr.. J.Eise1e. L.Matts. K.Raska. P.Saidi. UMDNJ-Robert Wood Johnson Medical School. New Bran-wick, NJ. The risk of heterosexual and perinatal transmission of HIV infection is a major public health concern and still not fully understood. From 1981 to 1986 ten hemophiliacs were diagnosed to have AIDS with a latency period of ranging from 27 to 60 months (median of 36 months) as determined by the time from the seroconversion to HIV to the onset of AIDS. Their spouses and children who were conceived and born during the latency period of AIDS are at risk for HIV infection. Five wives and 4 children conceived during the time of their fathers' seroconversion to HIV were identified and tested for HIV antibody and immune status following the diagnosis of AIDS were established. Four of 5 wives were negative for HIV antibody with normal ranges of T4 (729:133/cmm mean:s.d.). T8 (430:152).and T4/T8 ratio(2.0:0.6). One spouse with a history of multiple sclerosis and immunosuppressive therapy. but no other risk factors for HIV infection. was tested positve for HIV antibody by ELISA and Western blot technic. and reduced Tb (82/cmm) count while remaining asymptomatic. Your children from 2 families conceived while their fathers were positive for HIV antibody were also seronegative for HIV while maintaining normal T4 and T8 counts. This finding suggests that a large number of hemophiliacs through their exposure to contaminated clotting factors are at risk for HIV infection. but the risk of transmission to their spouses and children conceived during the the period of seroconversion to HIV may be small. Nevertheless. until the real magnitude of this risk is defined. a judicious measure to prevent the risk of transmission is warranted. THR83 Opportunistic Diseases in Florida AIDS Cases: Risk Groups and Time Trends DEBORAH HOLTZMAN, S. LIEB, R.A. STEVENS, G. METELLUS, J. SIMS, J.J. WITTE, Florida Department of Health and Rehabilitative Services, Tallahassee, FL, USA As of January 23, 1987, 2,050 cases of AIDS meeting the Centers for Disease Control definition were reported from Florida, of which 1,213 were homosexual] bisexual (HO/BI), 286 IV drug users, 251 persons born in "No Identified Risk" (NIR) countries, and 300 in other risk groups. For the total cases, 2,569 op- portunistic diseases were reliably diagnosed. An analysis of surveillance data was conducted to describe changes in the occurrence of selected opportunistic diseases by risk group. Five diseases accounted for 861 of the total: Pneumo— cystis carinii pneumonia (PCP) 461, Kaposi‘s sarcoma (KS) 16%, candida esopha- gitis (CC) 142, toxoplasmosis (TP) 51, and cytomegalovirus (CMV) 5%. The dis- tribution of each disease within the three largest risk groups was as follows: Disease PCP KS CMV Risk Grou (N-1201) (N-406) (N-hOS) (N-IGZ) (N-lol) Homosexual7315exua1 Male 56% 76% 421 All 501 IV Drug User 132 31 19% 141 8% Persons Born NIR Countries 91 61 14% 25% 102 From 1981-1986, the cumulative incidence of KS showed a slight decrease rela- tive to the other opportunistic diseases (17 to 141), a decline which was most pronounced among persons born in NIR countries. PCP increased over this time period (32 to 48%), mostly due to an increase of PCP in HOIBI males. GC showed a decrease after 1983, primarily as a result of a decline among persons born in NIR countries. Persons born in NIR countries also showed a decrease in TP and CMV. The clinical diagnosis and treatment of AIDS will benefit from maintaining a high index of suspicion for risk group-specific opportunistic diseases. 177 THRs4 Rapid spread of HIV infection in a rural district in North Uganda. F. DE LALLA*, MASSIMO GALLI, F. CIANTIA**, P.L. ZELI”, G. RIZZARDI— NI**, A. SARACCO et al., Clinic of Infectious Diseases, University of Milan, ”Infectious Diseases Department, St. Anna Hospital, Como, Italy, **Kitgum and Kalcngo Hospitals, Uganda. Spread of HIV infection in Central Africa is rapidly increasing: a rising nu! ber of AIDS cases and a high prevalence of anti-HIV antibodies have been receg tly demonstrated both in urban and rural areas. Results of a sero—epidemiologi cal survey in a rural district in North Uganda (East Alcholi) are reported. During 1984 sera were collected from 111 subjects living in a rural area of the disctrict and mainly affected with malaria or dracunculiasis. In 1986 another group of sera was obtained from 491 subjects including 50 inpatients affected with TB, 246 inhabitants of 2 small villages, 37 soldiers from an army settle— ment, 158 members of 3 hospitals staffs of the district (Kitgum, St. Joseph am Kalongo hospitals). Sera were tested by 2 commercially available ELISA methods and by IFA. In the ones resulting positive by at least one method, w.B. confi: mation was sought for. In the first group (1983-84), only 1 out of 4 ELISA po- sitive samples was WB confirmed (0.9%). In the second group (1986), overall pg sitivity rate was 13.2%. No significant differences were observed between the different groups: soldiers 17%, pregnant women 12%, TB patients 10%, Hospital staff 13.2%, rural population 13.8%. The great increase of anti—HIV seropositi vity in such a short time indicate the dramatic spread of the epidemic even in remote rural areas of Central Africa. THRBS HIV antibodies in blond bank donors, hamophiliacs, homosexual men, prostitutes and hemodialysis patients, in Brasil EQEMA_E;_E§I§IMHQ*, N.F. MENDE5*, A.S.D. NUNES*, C.C.C. GUERRA**, L.G. ROSEN- FELD**, N. HAMERECHLACK**, at al., *Escola Paulista de Medicine, Division of Immunology, 550 Paulo, SP, Brasil, **Centrd de Hematologia de 850 Paulo, 550 Paulo, SP, Brasil. In 22,245 serum samples from 550 Paulo City blood bank donors obtained From June 1985 to November 1986, studied by HIV ELISA test and H9 control plates (Electro—Nuclennics) and Abbott HIV Confirmatdry EIA, 40 (0.18%) were positi- ve. In 1986, 73.21% (41/56) of patients with hemophilia A (treated with local and/or imported factor VIII concentrate) and 30.9% (17/55] of homosexual. men From 850 Paulo were positive. No antibodies to HIV were found in 176 prostitu tes From 550 Paulo. The study of 938 serum samples from polytransfused hemp: dialysis patients from 550 Paulo, tested retrospectively From 1986 to 1976,re vealed that 1.51% (2/124) of the samples obtained in 1986 and 4.80% (5/104) in 1985 were positive; no positiveness was observed in sera from 1984 or pri- or to it. There were 6.18% (58/938) of False positive reactions due to antibo dies against H9 antigens.Serum samples obtained from patients with hemophilia A in Rid dE Janeim City during 1983—1984 revealed 98.24% (56/57) of positive ness to HIV antibodies (treated mainly with Factor VIII concentrate prepared From locally collected plasma). THPBG Tuberculosis and the Acquired Immunodeficiency Syndrome - ' Florida Hans L. Rieder*, A.E. Bloch*, C.H. Cole**, J.J. Witte**, D.E. Snider, Jr.*, *Centers for Disease Control, Atlanta, GA, **Department of Health and Rehabilitative Services, Talshassee, FL. To determine the impact of AIDS on tuberculosis morbidity in Florida, the State AIDS and tuberculosis registries were matched. of the first 1,094 AIDS cases reported from Florida through December 1985, 109 (10%) were determined to also have had tuberculosis. Tuberculosis preceded the diagnosis of AIDS in 572, was concurrent with in 28% and followed the diagnosis of AIDS in 16%. Patients with AIDS and tuberculosis (AIDS/TB) were younger than AIDS patients without tuberculosis (AIDS/non—TB) (median age 34 years vs. 35 years); were more likely to be black (81% vs. 21%) and less likely to be white (11% vs. 50%); were less likely to be homosexual/bisexual men (21% vs. 62%); and were more likely to be foreign—born (601) than AIDS/non—TB patients (25%). The 105 tuberculosis patients with AIDS (TB/AIDS) who were reported to have tuberculosis from 1981 to 1985 were compared to the 7,136 tuberculosis patients without AIDS (TB/non—AIDS) reported during the same period. TB/AIDS patients were found to be younger (median 33 years vs. 49 years) and were more likely to be black (791 vs. 51%) than TB/non—AIDS patients. They were less likely to have pulmonary tuberculosis (62% vs. 89%); were less likely to have pleural tuberculosis (0.1% vs. 3.01); and were more likely to have lymphatic (191 vs. 2.32) and miliary tuberculosis (9.5% vs. 1.3%) than TB/non-AIDS patients. These data suggest that tuberculosis is common in AIDS patients in Florida and that AIDS/TB patients differ in many demographic and clinical aspects from AIDS/non-TB patients and TB/non-AIDS patients. THURSDAY, JUNE 4 TH287 Descriptive Epidemiology of Acquired Immune Deficiency Syndrome Cases Among Native Born Black Persons in the United states Reported June 5, 1981- April 14, 1986 MENCER DONAHUE EDWARDS, Spectrum AIDS Education Project, Wash.,D.C. Research was undertaken to determine the descriptive epidemi— ology of AIDS cases among native Black Americans. From June 5, 1981 - April 14, 1986, 4,362 cases of AIDS were reported among Black persons born in the U.S. 4,195 were adults/adolescents, and i67 children. 2,510 of these are known to have died, a case fatali ty rate of 57.5%. Among adult patients, 41% were gay/bisexual males, and 39.31% intravenous drug abusers. Patients with Pneumoc stis carinii Pneumonia only accounted for 65% of all cases Over 40% resided inthe North-East SMSA. The annual incidence rate in this selected sub—population of Black cases was 0.85 cases per 100,000. Comparison with a control group consisting of the remain— ing 15,198 cases as of April 14, 1986 yielded statistically significant differences: the study group included 9.1% more females; 2.4% fewer cases age 30—49; 32.3% fewirgay or bisexual male patients; and 1.8% more cases in the 'no known risk group' category and 11.1% fewer and 10.6% more diagnoses of Ka osi's Sarcoma and Pneumocystis carinii Pneumonia only respectively. Implications of these results are‘dlscussed in light of recently described epidemilogy of all AIDS cases among Black persons ,native and non—native, in the U.S. THP88 HIV infections in rural areas of West Africa(duinea Bissau) F.ANTUNES‘,M_.QQEJ.E.§.ANIQ;EERREIRA*1M.H.LOURENCO*$C.COSTA***,M.PE- DRO****,*lnstituto de Higiene e Medicina TropicaI,Faculdade de Medicina de Lisboa, “Faculdade de Farmacia de Lisboa,***Ministerio da Saude,Bissau,****Hospital de San- ta Maria,Lisboa. In November 1985,5era from 98 individuals has been taken in two rural areas in Guinea Bissau,used for trypanosomiasis studies,and stored until now.ln the first area,Biombo,we studied «a sera from the inhabitants of village("tabanca")Cupedo,50 km from the capital Bissau.ln the second area,$.Domingos,in the north of the country,a few kilometres from the border of Senegal we studied 50 sera from the inhabitants of two villages,26 from "tabanca" Djugul and 24 from "tabanca" Colage. We used the ELISA and the Western blot both to HIV type 1 and HIV type Z,and the IFAT to HIV type 2 in the 98 Sara. HIV 1 antibodies were detected in 6 of 148 inhabitants of Cupedo(12.596),5 males and l female;in Djugul HIV 1 antibodies was detected in 1 female over 26 inhabitants(3.8%), and in Colage in 1 female over 24 inhabitantsill.296). In Cupedo we have finded 5 positive cases over ll8(lo.ll%)for HIV 2,1 male and 14 females; in Djugul HIV 2 antibodies were detected in 7 individuals over 26(26.996),l male and 6 females,and in Colage HIV 2 antibodies was detected in I female over Z‘I individualdlfisl. These findings indicates that HIV 1 and HIV 2 may be endemic in certain West Africa countries. THP89 Acute Infection by.H.I.V. in DrugfiAddicts. ' fl ' RAFFAELE PRISTERA' , C. SEEBACHER M. CASINI , A. LAZZARIN , *Department of Infectious Diseases, Bolzano, ‘ University Clinic of Inf. Dis., Milan; Italy The diagnosis was established in 17 out of 365 DA for onset of mononucleosis—like syndrome and of H.I.V.-Ab seroconvarsion. The duration of the acute illness ranged from 15 to 66 days. The incubation period was 2—3 months in 4 DA with chain transmission (syringe sharing among them and subsequent infection during this phase), but unknown in the other 13 for previous repeatedly sharing. Seroconversion occurred about 1 month after disease onset. The acute phase was characterized, when compared with control seronegative DA, by an increase of WBC (E: 9350), lymphocytes (not as relative countl) and especially of CD8 (i: 1626, 451) and by a moderate reduction of CD4. This picture might stand for the immune response to the infection, particularly characterized by the increase of the cytotoxic portion of CD8, as it happens during other viral infections (CMV, EBV, HSV). On the other hand, 3 patients did not show this picture: neither NBC, nor lymphocytes, nor CD8 (i: 935) were increased, whereas CDA were even more reduced. They had all a severe post-infectious chronic active hepatitis and thus likely a pre-existent alteration of the immune system (IS), which might have prevented CD8 from their cytotoxic response. Consequently the CD6 increase lack might suggest a functional failure of the IS, particularly of CD4, and predict an unfavorable evolution. As a matter of fact these 3 patients showed later on a CDk fall, which was considerably stronger, if compared with that of the other 13. 178 "“290 Comparison of a novel RIPA/SDS-PAGE to immunoblottinq and virusculture HAN HUISMAN, M.TERSME'ITE, N.LELII, C.V.d.POEL'. J.M.A.LANGE' and LIKED“. Central Laboratory of the Netherlands Red Cross Blood Transfusion Service, incorporating Lab. of Exp. and Clin. Immunology University of Amsterdam; 'Blood Bank Amsterdam; “Dept. of Med. Virology, University of Amsterdam. A RIPA using l~25I--labe1ed HIV antigens, enriched for gplZO/dlen" (GRIPA) was compared to immunoblotting (ID) for sensitivity and specificity for HIV antibodies. Sequential sera from 8 seroconverted homosexuals were tested. In all cases antibodies to gplZo/ll and more prominent to p24, were found. In two cases these antibodies were detected earlier than by In. It appeared that the GRIPA was 10 times more sensitive for anti-p24 in serial dilutions of eight serumsamples, while the detection of anti-gplzo/ll was similar in 13. In one of 78 randomly chosen BIA-negative sera from homosexuals, antibodies to p24 could be detected. This early seroconversion was confirmed three months later by ID. The specificity of the GRIPA was demonstrated by analyzing 10 EIA- negative sera from homosexuals collected during two years. All sera were found negative in the GRIPA and the persons revealed no signs of HIV infection. Six blood donors reactive for p24 in IE for two years but negative in the GRIPA, were also studied. Virusculture was attempted with six seropositive asymptomatics as a positive control group. 'flle six p24 13 positive persons were culture negative, while a 100‘ correlation existed between GRIPA and virusculture. It is concluded that reactivity in ID to p24 may be false positive, whereas reactivity in the GRIPA to p24 only is highly suspicious. This feature in addition to the high sensitivity for gplZO/il makes the GRIPA an useful confirmatory assay in sera with conflicting results in other HIV antibody assays. THP91 Mothers of Infants with HIV Infection: ' Pregnancies CHENDOLYN B. SCOTT. M.T. MASTRUCCI. S.C. HUTTO. W.P. PARKS, Department of Pediatrics. University of Miami School of Medicine, Miami. FL One hundred and thirty-four cases of perinatal HIV infection have been identified in South Florida between January 1981 and December 1986. These infants were born to 109 HIV infected women. Risk factors identified include drug abuse in 221 of the mothers and the remainder had no identifiable risk factor other than heterosexual contact with an infected person. All but one of the mothers were clinically well at the time of delivery of their first infant with HIV infection emphasizing that the infected child is frequently the first member of a household to be identified as infected. Subsequent to the birth of the index pediatric case 33 (302) of the 109 women have developed ARC or AIDS and 18 (171) have died. Twenty-five women have had ‘02 subsequent infants after the index case. Two women and their 3 children have been lost to follow-up. The remaining 23 women and their infants have been followed prospectively. Length of follow—up families ranges from 6 months to 5 years with a mean of 32 months. Fifteen women have more than 1 infected child. of the subsequent siblings. 21 (541) are infected and 18 (1061) are not infected. 0f the 21 infected siblings 12 have died (601). None of the unaffected siblings have died. Family patterns of disease include families that have 2 children with encephalopathy, one family that has 3 children with wasting syndrome and 1 family that has 2 children with severe lymphoid interstitial pneumonia. Infants born to HIV infected women who have delivered a previous HIV infected infant are themselves at significant risk for infection. These results may reflect a special population of women and further studies are required to determine also the risk of having an infected child in women without previously infected children. Outcome of Subsequent THRgz Heterosexual Transmission of Human Immunodeficiency virus (HIV): Relationship of Sexual Practices to Seroconversion. MARGARET A FISCHL, GM DICKINSON, A SBGAL, S FLANAGAN, M RODRIGUEZ. University of Miami, Miami, Florida. To evaluate the efficacy and potential role of condom use in the prevention of heterosexual transmission of HIV, spouses of patients with AIDS and AIDS- related complex were evaluated. Evaluation included a medical history, physical examination, standardised interview, and blood tests. All spouses were counseled and followed every lo months. Forty-seven eeronegative spouses were studied. Twelve were men and 35 were women. Hone had risk factors for HIV infection. The median length of followup was 18 months. Seventeen (361) developed antibody to HIV; 4 (331) were men and 13 (371) were women. The relationship of sexual practices after enrollment to the development of antibody to HIV is shown below. number HIV antibody percent positive negative converted abstinence 12 0 17 07. condom use 18 3 15 177. no condom use 17 ll. 3 827. The frequency of sexual intercourse and types of sexual activity were not different for spouses using condoms compared to those not using them. In evaluating couples who used condoms, breakage. improper use and fellatio without condoms was not uncommon. Although condom use appeared to decrease the rate of HIV transmission, seroconversion occurred. These data suggest that condom use may not afford complete protection against the heterosexual transmission of HIV. THURSDAY, JUNE 4 THEga Prevalence of HIV-1 and HIV—2 antibodies in a selected Malawian population LUTZ G. GURTLER, G. ZOULEK, G. FR'O‘SNER. F. DEINHARDT et a1., Max Von Pettenkofer Institute. University of Munich, Federal Republic of Germany and G. LIOMBA, H.J. SCHMIDT et al., Queen Elizabeth Central Hospital, Blantyre, Malawi Screening for HIV infections in Malawi was began in 1986 to evaluate the prevalence of HIV—1 and HIV—2 in this part of Africa. 96 antenatal mothers, 265 female prostitutes and 32 male prisoners were screened with a commercially available ELISA for HIV—1 and an ELISA prepared in our laboratory for HIV—2 using LAV-2, kindly provided by L. Montagnier. Positive reaction in the ELISA tests were confirmed by immunofluorescence and immuno- blot. In addition, the presence of markers of infection with other sexually transmitted agents, i.e. hepatitis B virus (HBV) and treponema pallidum (TPA) was determined. In: results are given in the table as positive/number tested (percent). markers for HIV—1 HBV TPA antenatal mothers 4/96 (4%) 67/96 (70%) 26/96 (27%) female prostitutes 148/265 (56%) 219/265 (83%) 143/265 (54%) male prisoners 10/32 (31%) 18/32 (56%) 11/32 (24%) 5046f the sera of prostitutes positive for anti—HIV—l also were screened for anti—HIV-2. Antibodies specific for HIV—2 antigens were not detected. However. crossreactions of anti—HIV-l with HIV—2 antigens were observed, particularly reactions of anti—HIV—l-p24 core with HIV—2-p27. The results show that infections with HIV, HBV and TPA are common in this part of Africa; but it is not justified to calculate from only 393 individuals investigated so far the prevalence of anti—HIV in the 7 million inhabitants of MalawL Ongoing studies should clarify this further. THP94 Berlin prospective Stuiy on 35 HIV (human immodeficiency virus) Antibody—Positive Newborns ILSE GROSSH—WURNER*,S.KOCH*,B.STUCK**,J.Woweries***,B.ZORR****,A.SCHAFER*****, et a1.,*Univer51t5ts-Kinderklinik Berlin,**Kinderklinik RVK Berlin,***Kinder— klinik Neukolln Berlin,****1nstitut far experimentelle Virologie Berlin,***** Universitdts—Frauenklinik Berlin The presence of HIV-IgG-antibodies (AB) in newborns (NB) of HIV-AB-positive mothers does not provide conclusive evidence of an actual infection with the virus. This is determinable only by longterm observation of the patients, con— cerned in accordance with immunological, virological and clinical criteria. Consequently, since July 1985, all NB of HIV-AB-positive mothers are being kept under close observation at the Berlin University Children' Hospital and 35 newborns have so far been icluded in the study. During an observation period of now over 18 months, none of the children ha- ve as yet contracted AIDS. A slight neurological abnormality was apparent in Z children.0ne child who suffered a bacterial meningitis at 11 months of age had become seronegative at 6 months of age. The HI—virus was identified in CSF at the time of meningitis despite further seronegativeness. One child whose clinical course was extraordinary (weight stagnation, re- currences of dandidiasis) died at 7 months(sudden infant death). As expected, 15 children whose virus culture was negative, became seronega- tive at between 3 to 7 months, however also 4 children with a positive virus culture became seronegative. The results clearly show that AB-Screening is not a sufficient method of course control, but that longterm observation is essential for accurate classification of HIV—AB—positive newborn children. THEgs The Geographic Distribution of Human Immunodeficiency Virus (HI!) Antibodies*in Parenteral Dig; Abusers (PD¢§2* W. ROBERT LANGE , B.J. PRIMM , F.S. TENNANT , J.T. PAYTE , c.u. Lunar”, J.H. JAEFE‘ et a1., 'NIDA-ARc, Baltimore, MD, “*ARTC, Brooklyn, NY, * Community Health Projects, w. Covine, CA, ****Drug Dependence Associates, San Antonio, TX, #DACCO, Tampa, FL. Opioid dependence treatment programs in 5 regions of the US collaborated in a study aimed at monitoring trends in seroprevslence of HIV antibodies. After informed consent, 1,650 PDAs volunteered to provide blood specimens and data on health history and patterns of drug use. While this sample cannot purport to be representative of PDAs in the region, nor even of PDAs in treatment within the region, the wide disparities in HIV seroprevelence in the face of similarities In drug using behavior have important implications for prevention. In the New York ere: (Harlem, Brooklyn), 611 of samples (N-280) obtained in late 1986 were positive, up from 501 of samples (N-SBS) from the same program taken In early 198A. In Baltimore, 29% of samples (N-IBB) representing 11 programs were positive. Significant sex and ethnic group differences were apparent. In contrast, samples from programs distant from the Northeast corridor had for lower rates: San Antonio, 21 (N-loo); Tampa, 01; Southern Csllfornis, 1.51 (N-AIS, with samples from programs from Fresno to San Diego). Contrary to expectations, there was no corresponding difference in lifetime needle sharing experiences, which ranged from a low of 701 in New York to 992 in San Antonio. Because needle sharing is practiced by FDA: in areas where seroprevalence is still relatively low, these areas are vulnerable to the same catastrophic spread seen in the Northeast. But a window of opportunity where prompt, vigorous, and aggressive efforts at prevention could have major Impact. 179 0 ROSENGREN, M O'SHAUGHNESSY, THPQB IgM Antibodies to HIV in Sera from HIV-Infected Homosexual Men in Montreal SNEE—LENG TAN, D EYMARD, N GILMORE, M ROZAKIS, S JOTHY, E GOLDBERG, R LEBLANC, P GILL. Division of Clinical Inmunology and Department of Pathology. Royal Victoria Hospital, McGill University, Montreal; Laboratory Centre for Disease Control, Ottawa, Canada Sequential sera from 163 homosexual men, infected with HIV confirmed by 196 seropositlvity, were assayed for lgM antibodies to HIV. They were selected from a private practice, and consisted of 28 men who IgG-seroconverted; 12 men who reverted from IgG—seropositive to negative; and 123 men who were persist- ently IgG-seropositive. 133 men were asymptomatic at the time of serum collec— tion; 30 men had ARC; and 10 later developed AIDS. Duration between serum samples was 9.8 months i 4.6 (SD). IgM antibodies were detected by IgM-ELISA after rheumatoid factor adsorption. Cut-off for this assay was 7 SD above the mean of IgM-seronegative controls. Specificity of IgM antibodies was confirmed by IgM-western blotting. IgM antibodies were detected in the sera of 14 men, or 8.6% of this cohort: 2 of 28 men who IgG-seroconverted, including one man who had IgM antibodies when IgG antibodies were undetectable; none of 12 men who IgG-seroreverted; and 12 of 123 men who were persistently IgG-seropositlve, including 3 men who develop— ed IgM antibodies when already IgG—seropositive and 6 men who remained persist- ently IgM-seropositive. 8% of asymptomatic men, 10% of men with ARC and 10% of men who subsequently developed AIDS had IgM antibodies detectable in their sera. western blotting showed IgM antibodies reacted with recognized HIV anti- gens but with a different pattern than that of IgG antibodies. These data show that IgM antibodies to HIV are detectable at low frequency in sera of HIV—infected homosexual men, and appear unrelated to 196 antibody responses or to HIV disease manifestations. THB97 High Prevalence of Serum Antibodies to HTLv-III p66/p51. A.L. DeVICO', P. diMARZO VERONESE’, R.C. GALLO", M.G. SARNGADHARAN', 'Bionetice Research, Inc., Rockville, MD; **Lab. of Tumor Cell Biology, NCI, Bethesda, MD. The reverse transcriptase of HTLV—III is detected in immunobloc assays as a pair of 66 RD and 51 kn proteins (p66/p51). These proteins share a common NH; terminal amino acid sequence; whether both proteins are enzymatically active has not been determined. A preliminary study indicated a high seroprevalence of RT antibodies in HTLV-III antibody—positive individuals tested by the viral immunoblot technique. Further, some individuals had serum antibody reactivity with only p66. To more accurately determine the frequency of serum antibody reactivity with RT, the results of 700 immunoblot assays of HTLV—III antibody-positive sera were examined. Seropositivity was determined by reactivity with gp4l, p24 or both. of the sera selected, 79% were positive for antibodies to p66/p51. Such immunogenicity for RT has not been demonstrated for any noncytopathic mammalian retroviruses including HTLv-I and —II. The seroprevalence of reactivity with RT seems to vary with the stage of the disease. out of the 700 sera 360 for which a diagnosis was available were divided into 4 groups consisting of asymptomatic individuals at high risk, ARC patients, AIDS patients and AIDS patients with Kaposi sarcoma. Seroreactivity to p66/p51 was found in 75%, 85%, 771, and 78% of the individuals in each group, respectively. Serum from the individuals with antibody reactivity to only p66 were retested in an immunobloc assay using purified enzyme bound to nitrocellulose. All of the individuals tested had serum antibody reactivity with p51 but the level of reactivity remained much lower than that for p66. THPgs Recreational Drugs and HIV Infection: Relationsh1p to Risk of Infection and Immune Deficiency. Cladd E. Stevens, Patricia E. Taylor, Santiago Rodriguez and Pablo Rubinstein. New York Blood Center, 310 East 67th Street, New York, New York, U.S.A. In early 1984 the Laboratorles of Epidemiology and Immunogenetlcs at the New York Blood Center began a prospective study of the acquired immune defi- ciency syndrome (AIDS) in a cohort of 850 homosexually active men in New York City. At the time of entry into the project in 1984, each participant com- pleted a self—administered questionnaire which contained quantitative questions regarding use of 21 recreational drugs or categories of drugs, including amyl and butyl nitrite. Participants have returned every four months at which tlme an interim hlstory is obtained and cellular immune function is assessed. At the time of entry 42.3% of the men were anti-HIV positive. Anti-HIV prevalence at that time correlated with the use of each of the 21 recreational drugs for which we solicited information. However, recreational drug use also correlated with sexual activity, Including numbers of sex partners and fre- quency of high risk sex practices, factors which were the strongest predicters of anti-HIV positivity. No consistent association between hlstory of use of any drug and defects in cell mediated immunity detected among anti-HIV positive men at entry was observed. Over the past two-and-a-half years, 47 of the participants have been diagnosed as having AIDS. No association was found among the anti-HIV positlve men between history of drug use and the subsequent development of AIDS. These preliminary data suggest that the relationship between recreational drug use and the risk of HIV infection ls secondary to the association with sexual activity and that drug use had no subsequent influence on the develop- ment of defective CMI or AIDS. THURSDAY, JUNE 4 THEgg Correlation of HIV Isolation Rate and Stage of Infection. E REDFIELD, DC WRIGHT, NC mu, DS BURKE, mm, Washington, DC. HIV infection causes a spectrum of disease which can be placed in a working framework of progressive stages of viral-induced immune dysfunction as proposed by the Walter Reed Staging Classification. We investigated the ability to isolate HIV from perphsral blood mononuclear cells (PBMC) of patients with different stages of HIV infection. All retroviral cultures were performed and interpreted blindly with respect to clinical status. Cultures were performed using patient PBMC obtained by Ficol hypaque separation from 30 ml of whole heparized blood which were co cultivated with FHA-stimulated normal donor PBMC. Cultures were monitored for viral production by both reverse transcriptase and HIV antigen- specific assays for 30 days. Results are summarized in tables below. TABLE 1 TABLE 2 WR STAGE N #POS ZPOS TM: N 508 ZPOS l 3 0 OZ >800 8 i 131 2 34 9 262 600-799 16 2 131 3 3 1 331 400-599 13 6 461 4 3 l 332 200-399 6 3 50% 5 6 5 831 100-199 5 3 602 6 5 4 80% (100 6 5 831 TOTAL 54 20 372 TOTAL 54 20 37% These data demonstrate a significant correlation (P<0.001) of the ability to isolate HIV from PMBC with (1) Walter Reed stage and (2) T-helper cell number. The biological explanation of these differences is currently under investigation. THE‘IOO Serial T Cell Phenotypes in Homosexual Men Who Did or Did Not Progress to AIDS. JANET K.A. NICHOLSON, T.J. SPIRA, B.M. JONES, J.S. MCDOUGAL, Centers for Disease Control, Atlanta, GA. A cohort of 75 HIV-antibody-positive homosexual men with chronic lymphadenopathy has been studied serially for the last 3-4 years in Atlanta. As of January 1987, 21 have developed acquired immunodeficiency syndrome (AIDS). To determine whether those who developed AIDS are immunologically different from those who did not develop AIDS, we retrospectively examined the distribution and number of subpopulations of CD4 and CD8 lymphocytes in 5 men who progressed to AIDS and 10 men who did not over the last 3-4 years. Two-color immunofluorescence studies were done with combinations of monoclonal antibodies to detect functionally defined subpopulations of CD4 cells (helper-inducer [CD4+ABA+], suppressor-inducer [CD4+2H4+], and "activated" [CD4+HLA—DR+]), CD8 cells (cytotoxic [CDBILeuIS'], suppressor [bright CD8+Leu15+], "reactive" [CD8+Leu7+], and "activated” [CD8+HLA-DR+]), as well as phenotypes associated with natural killer (NK) activity (dull CD8+Leu15+ and Leu7'Leull+). c134 cells declined more rapidly in patients who progressed to AIDS, than in those who did not. None of the CD4 subset, CD8 subset, or NK-associated subset enumerations clearly distinguished progressors from nonprogressors. However, each progressor had a unique phenotype change that progressed with time, such as a severe depression in Leuli+ cells, increases in CD8+HLA—DR+ cells, increases in the proportion of CD3 cells that are Leu7+, and the proportion of CD4 cells that are 534+ or 2H4+. These changes were seen in only 2 of the 10 nonprogressors; the remaining 8 had stable phenotypes. These unique changes may reflect a failing immune system. TliP101 Abnormal Lymphokine Activated Killer Cell iLAK) Induction in - Peripheral Blood Mononuclear Cells (PBMC) in Patients Infected with the Human Immunodeficiency Virus (HIV) ALAN LANDAY‘, J. HARRIS‘, L. FALK**, D. PAUL**, H. KESSLER*, D. BRAUN‘, et a1. *Hush Medical College, Chicago, IL, and **Abbott Laboratories, North Chicago, IL The ability to generate LAK cells from the PBMC of asymptomatic homosexual males (AHM) with serologic evidence of HIV infection (n=25) was evaluated. HIV infection was determined by the presence of antibodies (Ab) to HIV proteins or by the presence of HIV core antigen (Ag). LAK cell generation was normal in HIV Ab+ Ag‘ AHM (mean $ cytotoxicity = ”6:13 compared to a control group of seronegative AHM where mean 1 cytotoxicity s ”5116). In contrast, the LAK cell induction was significantly impaired in AHM who were HIV Ab+ Ag+ (mean I cytotoxicity = 1629, p<0.01 compared to controls). The mechanism for suppressed LAK induction was evaluated and found to be due to an indomethacin (indo) sensitive suppressor function. Thus, the addition of indo to cultures of cells from Ab+ Ag* AHM restored their LAK function to control levels (mean % Cytotoxicity = u6:9). The presence of this indomethacin sensitive suppressor in Ab* Ag+ AHM was also documented in mitogen stimulated blastogenesis and IL—2 production assays and was correlated with significant depression of monocyte HLA-DR expression (321111 LeuM3+ HLA-DR+ monocytes vs 821155 LeuM3+ HLA—DR+ monocytes in controls, p<0.01). The deficits in LAK cell induction and mitogen stimulated blastogenesis which were observed in the group of patients who were Ab+ Ag+ were associated with HIV recovery from the monocytes of these individuals. These findings have important implications for our understanding of the pathogenesis of HIV infection and may point the way to new methods for therapeutic intervention. 180 THR102 Immune Response and Challenge of chimpanzees Immunized with a gplol Synthetic Peptide. W“, ’l‘.C. CHANH‘, P. KANDA*, J.W. EICHBERG*, R.C. KENNEDY*, J.S. ALLEN**, et 31. *Southwest Foundation for Biomedical Research, San Antonio, Texas, **Harvard School of Public Health, Boston, Massachusets. Two chimpanzees were immunized with a synthetic peptide containing amino acid residue 735-752 of gpbl transmembrane glycoprotein of HIV coupled to KLH. A third animal was inoculated with an unrelated peptide KLH conjugate. Both animals immunized with the gp51 peptide produced an antibody response which reacted with native gphl and gplGO. The three animals were challenged with HIV-NYS isolate after injections of immunogen and have been studied for 24 weeks post challenge for antibody response and virus isolation. Antibody response to viral protein p2h and gplZO was similar between the con- trol animal and the first peptide immunized animal. However, antibody to these proteins were delayed approximately 4 - 6 weeks in the second animal. Virus isolation studies are in progress e "“3103 Pediatric HIV infections in HIV-ELISA negative individuals: a report of 10 cases. W.BORKOWSKY,K.KRASNSKLD.PAUL*,T.MOORE,D.BEBENROTE AND S. CHANDWAN'L NYU-Be‘flevue Hoqital Ctre. New York, NY, *Abbott Laboratories, North Chicago. 11. The presence of HIV specific antibody has been used mdowment HIVinfection in patients. Both ELISA and im mumfluoresoence (IPA) have been used for screening. Rarely, sera considered negative by HIV-ELJSA assay is found to be reactive with vbnss ' bandson Wemn Blot asay (WE). Although these asayscangoduoe false positive reams in children below 1 year of age due to the presence of trargflaoenfany derived maternal HIV specific 196, we have found that false negative rm may be more com men than previously saspecbed. we have identified about 90 children infected with HIV. Ten of these were considered to be HIV-ELISA negative but found to pm HIV antigen in their plans, as memed by an antigen capmre ELISA way, with estimated viral antigen ooncentratiom of 13 to 756 pg/ml. Five of the ten have died of AIDS. Nine of the ten were born to drug abusing mothers. Five of the mothers had HIV- ELJSA antibody tests performed on their sera and all were positive. Nine of the children had decreased helper T cells. IPA performed on 6 of the sera was negative. WE asays performed on 5 of the sera were negative. Four of the children had axpporfing evidence of HIV infection as determined by the presence of and p121 antibody found with a com mercial any which employs recombinant antigen (ENVACOR). Since HIV infected infams have impaired primary antlbody responses to other antigens. a comparably imgxfired response to HIV antigens niay resultin negative antflxady assaysr HIV anthgen measurement appears to be an important bonito identify these infants. THP104 viruses of Human Immunodeficiency Virus Family Induce Expression ' of Class II Major Histocompatibility Complex Structures on Infected Target Cells 52 Vitro MARI KANNAGI, NORVAL W. KING, NORMAN L. LETVIN, Harvard Medical School, New England Regional Primate Research Center, Southborough, MA. The human immunodeficiency virus (HIV) and the closely related simian immunodeficiency virus (SIV) induce profound immune dysfunction in primate species. We have now shown that cell populations infected $3 vitro with these viruses exhibit increases in major histocompatibility complex (MHC) class II antigen expression. Cell lines chronically infected with both the monkey and human viruses express substantially more MHC class II but not more lineage—restricted or activation antigens on their membranes than do uninfected cell lines. No serologic cross-reaction was observed between MHC class II and viral specific antigens. MHC class II induction does not appear to be mediated through the production by infected cells of a soluble factor such as gamma interferon. Studies of the kinetics of antigen expression by cell lines following SIV-infection indicate that induction of MHC class II structures is a late event. Immunoelectronmioroscopy revealed that MHC class II antigen is expressed not only on the surface of the SIV-infected cells, but also on the envelope of virus particles derived from those cells. MHC antigen expression on virus infected cells and expression of those determinants by the virus may play a role in the pathogenesis of AIDS and the autoimmune abnormalities observed in HIV infected individuals. THURSDAY, JUNE 4 Tl'E105 CORRELATION 0F DELAYED HYPERSENSITIVITY SKIN TESTING AND ABSOLUTE T4 NUMBER AND T4/T8 RATIO. D.L. Birx, J. Rhoads, L. Smith, C. Wright, D. Burke, R. Redfield. Walter Reed Army Medical Center and Walter Reed Institute of Research, Washington, D.C. USA. We have evaluated 400 consecutive HIV ELISA and Western Blot confirmed seropositive patients who presented for evaluation and staging. Each indivi- dual underwent anergy screening with simultaneous, absolute lymphocyte and T4 counts, and T4/T8 ratio. The anergy panel consisted of PPD STU, two concentration of tetanus toxiod (TT) and candida albicans (CA) 0.1Lf, 1.0 Lf and 1:10 w/v 1:100 w/v respectively, mumps, and trichophyton. 5x5 mm indur- ation was considered positive at 48 hrs. Complete data is presented on 337 patients in tabular form. skin test results (n) T4 (#lmm3):SDx2 T4/T8 ratio 1 SDx2 1. energy 45 172 t 152 .27 i .20 2. TT (lLf)CA(l:10 w/V) 39 412 i 237 .56 1 .39 3. 1/5 61 481 i 299 .64 i .41 4. 2/5 77 530 i 250 .64 1 .29 5. 3/5 TT (0.1 Lf) 71 637 i 263 .84 1 .46 6. 4/5 CA (1:100/v) 39 614 i 374 .75 i .46 7. 5/5 5 550 i 160 .67 i .31 There is statistical significance between the T4 counts and ratios of those who are anergic and all other categories p<0.01, as well as, those who are only positive to the higher concentration of TT and CA (# 2 vs # 5) p( 0.05. A trend can be seen between the number of positive skin test responses and T4 counts and T4/T8 ratios. All individuals are being followed for correlation with disease progression. TliE106 Anti Nucleo-Capsid antibodies and S-HIV antigenemia: correlations with blood T4 cell counts and clinical status. D. MATHEZr. D. PAULsr, G. SAIMOTris, D. JAYLE**r*. g. EEIEQHIIQHt- *HOpital Ragmond Poincare, Garches, FRANCE: **ABBOTT Research and Developpment. Abbott Park, III, USA; ***HOpita1 Claude Bernard. Paris, FRANCE: ****H0pital Tarnier,— Paris. FRANCE. Serum HIV antigen concentration was measured bg immune capture where untrea- ted serum is incubated with solid phase human anti-HIV IgG and further reacted with rabbit IgG recognizing HIV (mainlg) core antigen (P24).Anti-Nucleo-Capsid antibody aesag used recombinant (mainly) P24 protein (solid phase) and competing human anti-HIV lgG. Inhibition > 65% that of anti-HIV IgG arbitra- rilg defined a high (affinity/titers) NCA antibodg specimen (H-NCA— Ab). A reciprocal distribution between S-HlV-Ag and H-NCA‘Ab was found: 71 S-HIV- Ag positive among 98 without H—NCA—Ab compared with 6/57 with H—NCA— Ab (60% versus 11.5%). S—HIV—Ag was detected in 41/72 patients with T4 7UU while H-NCA—Ab were detected in 16/62 and 53/90, respec- tively. Among patients without H—NCA—Ab. S-HIV-Ag distribution was independent of T4 counts. These results suggest that S-HIV-Ag may contribute to declining anti-Core antibodg (in our seriallg tested patients) but that it is not a main factor in the pathogenesis of T4 lymphopenia. In contrast. 12/18 Kaposi patients with T4>200 had detectable 5- HIV-Ag compared with 36/111 non-Kaposi patients. Conversely H-NCA-Ab were found in 3/20 Kaposi patients vs 102/195 non KaposillSZ vs 52%).Soluble viral products could play an active part in pathogenesis of Kaposi independentlg of the process leading to T4 lgmphopenia. Accordinglg, H-NCA-Ab would act as anti— kaposigenic factor. THR101 The Thymus-AIDS Connection: HIV p17 Protein Contains an Epitope Immunoreactive with Antisera to Thymosin a1 and HGP-30, a Synthetic gag Peptide Analogue PAUL H. NAYLOR*, A.L. GOLDSTEIN*, P.S. SARIN**, M. BADAMCHIAN*, S. WADA*, C.W. NAYLOR* et al., *The George Washington School of Health Sciences, Washington, D.C., **National Cancer Institute, Bethesda, MD. The p17 protein of Human Immunodeficiency Virus (HIV) contains an epitope which.has a 44-501 homology with an 18 amino acid region of thymosin a (To ), a thymic hormone. Using solid phase peptide synthesis we have syn hesized a 30 amino acid analogue of this p17 epitope which we have termed HGP-3O (HIV p17 gag synthetic peptide - 30 amino acids). Using high performance liquid chromatography, redioimmunoassay (RIA), and Western blot analysis, the presence of this immunoreactive epitope in a 17,000 dalton protein from an HTLV-IIIB viral extract has been identified. No significant immunoreaotivity was found in a number of other retroviral extracts including those obtained from feline, bovine, simian and murine retroviruses. These results, coupled with our previous studies demonstrating immunoreactive but non-authentic To -like material in serum from viral infected individuals at risk for or wi h frank AIDS confirms our hypothesis of a Thymus-AIDS connection. The demonstration that an antisera to HOP-30 cross-reacts with HGP-30 but not with To , and identifies the same protein as a p17 monoclonal antibody suggest ihat an ELISA or RIA can be developed that would be diagnostic for the presence of antibodies or antigens in individuals that are seropositive for the AIDS virus. (Supported in part by grants and/or gifts from the NCI (CA24974), Alpha 1 Biomedicals, Inc. and Viral Technologies, Inc.) 181 THP108 Intrathecal Synthesis of IgG Ollgoclonal Bands with Specific Activity Against Human Immundeficiency Virus (HIV) in AIDS Patients with Encephalopathy MAURO CERONL G.STONE,P.HCCARDO,D.MADDEN,J.SEVER,MNCD& NIH, Bethesda, MD. Involvement of the nervous system, including encephalopathy, is increasingly recognized as a frequent finding in AIDS. Evidence is accumulating that the HIV virus not only attacks the immune system but also affects the central and peripheral nervous system. The pathogenesis of the neurological damage however is very poorly understood. It has been demonstrated that HIV antigen and specific antibodies can be found in cerebrospinal fluid (CSF) with and without signs of encephalopathy. Usually encephalopathy is accompanied by lntrabhecal synthesis of IgG as demonstrated by quantitative indices of IgG and appearance of ollgoclonal IgG bands in CSF. Our studies using lsoelectric focusing of serum and CSF from patients with AIDS-related encephalopathy confirmed the presence of oligoclonal IgG banding. Some bands were common to serum and CSF and others present only in CSF. Using an immunoblot technique employing HIV precoated nitrocellulose paper, we have also demonstrated the presence of several HIV specific IgG bands in the sera and CSF of patients with AIDS-related encephalopathy. Most HIV antibody bands are present in both serum and CSF; some are present exclusively in the serum or CSF. Negative controls included sera from patients with gammopathy and HIV antibody positive samples blotted to nitrocellulose paper precoated with control, non-infected H-9 cell culture preparations. These findings demonstrate that HIV antibodies develop in the CNS and specific B-lymphocyte clones are stimulated to produce monoclonal IgG antibodies to HIV in the CNS. These findings strongly support a direct causative role of HIV in AIDS-related encephalopathy. THR109 Differential Susceptibility of CD4+ T Lymphocyte Clones to HIV Infection GERALD LINETTE*,S. KOENIG**,F. ROBBINS*,T.FOLKS**,R. HARTZMAN***,A. FAUCI**; *Georgetown Univ., Washington, DC; **NIH, NIAID, and ***NMRI, Bethesda, MD. It has been reported that only 10-15% of normal circulating lymphocytes will avidly bind and support replication of HIV in vitro. To evaluate the differ- ential susceptibility of T4 cells to HIV infection, a panel of 10 CD4 CD8 , IL-Z—dependent alloreactive clones were generated from a healthy HIV seroneg— ative volunteer. The clones were infected with HIV-1 at a multiplicity of in- fection of 0.1 and 1.0. HIV infection was monitored for 21 days by examination of cultures for cytopathic effects and by assay of supernatants for reverse transcriptase (RT). Eight of 10 clones showed no evidence of HIV infection. Two clones, one supporting HIV replication (CL62) and another showing no evidence of infection (CL40), were used for subsequent studies. Prior to exposure to HIV, both clones expressed similar levels of CDA, HLA-DR, and TAG antigens 3nd showed comparable levels of alloantigen specific-proliferation in a 4 hour H-TdR incorporation assay. Fourteen days following HIV infection of CL62, peak RT activity was measured. Ten to 50% of these cells were infected as detected by in situ hybridization for HIV RNA. No viable cells were present in these infected cultures after 30 days. In contrast, CL40 produced no detect- able RT activity or HIV proteins in an antigen capture assay and continued to proliferate and expand 2-3 fold over the same time interval. However. 0.1% of CL40 cells contained HIV RNA by in situ hybridization and virus from the cell free-supernatants of these cultures could be passaged to normal FHA-stimulated lymphocytes. Differential susceptibility to infection of normal T4 cells with HIV may be determined by cellular factors exclusive of specific receptor expression (CD4) and cellular activation. 1112110 Abrogation of Mitogen Response of Normal Lymphocytes by Anti- lymphocyte Antibody Positive Sera of AIDS and ARC Patients. BRENT DORSE'I'I‘, DAVOR SKLIZOVIC, WILLIAM CRONIN, HARRY L. IOACHIM, Department of Pathology, Lenox Hill Hospital, New York, H.Y. We have previously reported the presence of elevated levels of antilymphocyte antibodies (ALA) in the sera of patients with acquired immune deficiency syndrome (AIDS) and AIDS related complex (ARC). In addition we have demonstra- ted that ALA are statistically linked to disease progression. In order to determine whether sera containing elevated levels of ALA might affect lymphocyte function we have examined their effect on the mitogen response of normal peripheral blood lymphocytes. Whole blood from healthy volunteers was cultured in RPMI 1640 in the presence of mitogenic levels of Phytohemagglu- tinin (PHA). Cultures were treated with.ALA positive AIDS and ARC sera as well as ALA negative control sera. At various intervals galls were harvested and hypotonically lysed in the presence of Propidium Iodide. After treatment with Ribonuclease the relative level of lymphocyte stimulation was determined by flow cytometric measurement of the proliferating cell compartment. The mitogenic effect of PI-IA on normal lymphocytes was substantially reduced by treatment with ALA positive sera. Reductions varied from 40 to 95%. Treatment with ALA negative sera failed to affect mitogen response. THURSDAY, JUNE 4 T|1R111IDENTIFICATION AND CHACTERIZATION OF AN IMMUNODOMINANT EPITOPE ON THE GPAl HIV ENVELOPE PROTEIN. R. WISNIEWOLSKI, P. D. CHEN, J.G. WANG, W.WALTERS AND C.Y.WANG. United Biomedical, Inc. Lake Success, N.Y. We have previously identified a peptide 21 residues in length corres— ponding to a highly antigenic segment of HIV gp41 envelope protein(PNAS 83: 6159,1986) and included this peptide in a synthetic mixture as the solid phase immunoadsorbent for the detection of anti-HIV in individuals with HIV infection. When this peptide was conjugated to a protein carrier (HSA) and used as an immunogen, high level of antibodies directed against this peptide was found to cross-react with the whole HIV lysate. When attenuated HIV was used as the immunogen, after fusion with NS-l myeloma cells, a high frequency ( 80%) of monoclonal anti—HIV antibodies screened out by Enzyme Immunoassay on HIV lysate fixed plates were found to be negative by Western Blot (WB) analysis. These BIA—positive WB—negative HIV antibodies, frequently discarded by investigators due to their seemingly low affinity nature, were found to react specifically with the Zlmer antigenic peptide. Further analysis of these monoclonal anti-HIV gphl antibodies, developed through immunization with either the peptide-conjugate or the HIV lysate, with peptide analogs of this Zlmer has enabled us to precisely delineate each of their corresponding epitopes at a single amino acid level. Although no inhibition of HIV binding to CEM-T cells were observed with these antibodies, preferential recognition of this gphl epitope may indicate an important functional role of this region in the initiation of an immune response through antigen presentation or T cell activation. THR112 UV—HIV Immunosuppression of Mitogen Responses by Normal PBL Can Occur in the Absence of Cytopathology NASAR QURESH , R.F. GARRY, and L.A. HENDERSON, Department of Microbiology and Immunology, Tulane Medical School, New Orleans, LA. Decrease in T4 cells cannot account for the full extent of the immune defects seen in AIDS or ARC patients. Immune defects can be demonstrated in seropositive patients with T helper/T suppressor cell (TA/T8) ratios in the normal range. Normal peripheral blood lymphocytes (PBL) incubated with PHA and uv-inactivated HIV (UV-HIV) were examined with specific monoclonal antibodies to various T cell subsets by flow cytometry. Three out of 7 individuals tested exhibited a 25-30‘ decrease in Leu 3a positive cells, and a marked decrease in T4/‘I‘8 ratios over a 7 day incubation period. This decrease was accompanied by a varied but consistent increase in Leu 2a positive cells. Preactivation of PBL's with FHA alone and subsequent ex— posure to UV—HIV in the presence of FHA exhibited inconsistent Leu 3a killing and T4/T8 ratio changes in susceptible individuals tested in repeated experi- ments. The effects of UV-HIV on the proliferation of normal PBL's cultured in the presence of PHA were studied. UV-HIV, intact or detergent solublized, suppressed PHA stimulated proliferation of donor PBL's over a broad range of PHA concentration even in the absence of cell killing. This effect was dependent upon the quantity of UV-HIV or solublized UV-HIV. The elaboration of a putative suppressor factor from cultures of UV-HIV treated PEL's in the presence of PHA will be discussed. Demonstration of marked immunosuppression in the absence of Leu 3a killing and changes in T4/TB cell ratio, indicates the possibility that the two phenomena may be mediated by two different proteins or the same protein may serve several functions. TllR113 Patterns of Lymphocyte Subset Alterations in SIV/Delta Infected Rhesus Monkeys. LOUIS N. MARTIN, M. MURPHEY-CORB, E.A. WATSON, G.B. BASKIN, Delta Regional Pri- mate Research Center, Tulane University, Covington, LA. U.S.A. Simian Immunodeficiency Virus (SIV/Delta) infection of rhesus monkeys induces immunodeficiency, opportunistic infections (OI) and death. 01 manifestation postinoculation varies from 2 to 21 months. Studies of lymphocyte subsets by staining with monoclonal antibodies revealed two patterns of alterations in SIV/Delta infected monkeys, one of which may be prognostic of imminent OI. Monkeys dying with OI by 8 nths after SIV/Delts inoculation geveloped in- creased percentagee of T—ll (erythrocyte receptor) and Leu 25 (suppressor/ cytotoxic) cells. Depressed helper/guppressor (H/S) ratios resulted from the increase in the percentag of Leu 2a cells. Although these animals had nor- mal percentages of Leu 38 (helper/inducer) cells, the percentages of these cells staining with 434 was decreased, indicating a defect in s more restricted helper/inducer subset. Five of the 7 inoculated monkeys which exhibited this pattern of subset alterations died within 8 months postinoculation, and 4 of the 5 monkeys which died also had progressive decreases in serum IgG concentra— tions. Monkeys phich survivsd longer than 8 months developed decreaged per— centages of T-ll and Leu 3a cells and increased percentages of 3—1 cglls. Depressed H/S ratios in this group resulted from the decrease in Leu 33 cells. Although the percentage of Leu 33 cells was depressed, the percentage of these cells staining with 434 was normal. All 6 inoculated monkeys which exhibited this pattern of subset alterations. including increased B-cell percentages, had progressive increases in serum IgG. One monkey in this group died 309 days postinoculation with a B—cell lymphoma. Seven of 9 monkeys tested had defec- tive antibody responses to tetanus toxoid. 182 THP114 Cellular Pathogenesis Induced by Human Immunodeficiency Virus DOROTHY B. LEWIS“, B. YO?FE°. C.G. BOSHORTH‘. F.B. HOLLINGBR°. & R.R. RICH“. *Howard Hughes Medical Institute. Departments of Microbiology & Immunology and °Virology, Baylor College Medicine. Houston. TX. USA. He developed an in vitro system to study cytopathology induced by human immunodeficiency virus (HIV). We mixed an irradiated infected tumor cell line. H9. with peripheral blood mononuclear cells (PBHCs) and monitored the phenotype of lymphocytes. Rapid reduction of CD4+ numbers occurred after 3-5 days in cultures containing irradiated H9/HIV. In contrast, no depletion occurred after incubation with K562 or uninfected H9 cells. Similarly, no depletion occurred after incubation of H9 cells with free virus in 5 days. Because we thought that antigen activation might play a role in the rapid CD4 depletion and because the quantity of free HIV may be different from that associated with H9/HIV cells, we examined the response to irradiated infected PBHCs. Allogeneic or autologous mixtures of PBMCs from person "A" or 'B' were examined in cultures containing irradiated infected cells from person "B". In some A + B/HIV cultures, we noted dramatic depletion of cells within 5 days; in others only a modest reduction occurred. In B + B/HIV cultures, however, no reduction in CD4+ numbers occurred after 5 days in culture although surface interleukin-2 receptor expression did occur. We, therefore, used PHA or CD3 Sepharose to provide a T cell receptor signal to the B + B/HIV cultures. We found that dramatic depletion of CD4+ numbers occurred after PHA addition. coa also induced CD4 cellular depletion but to a lesser extent than did PHA. These results suggest that HIV must be associated with cells for optimal cytopathology and that lymphocyte activation, perhaps via allogeneic recognition. may be a primary mechanism involved in the acquisi- tion of HIV in vivo. Supported by NIH grants A122549 and A121289. "“3115 Antibodies to HIV are produced within the Central Nervous Systan of ' all subjects with all categories of HIV Infection ANDREI] LLOYD, J.M. DIIYER, P. ROBERI'SOI, D. WAKEFIELD, Departments of Clinical Innunology and Pathology, The Prince Henry/Prince of wales Hospitals of the University of New South Wales, Sydney, Australia. Anti—HIV antibodies were found in the cerebrospinal fluid of all 41 subjects tested whose serum contained these antibodies. 1b ensure that locally produced antibody was being detected, a sensitive assay was used to demonstrate the integrity of the blood—brain barrier. Antibodies to ubiquitous adenovirus group antigens were sought, sinultaneously, in CSF and serum. A lack of adeno— virus antibodies in CSF of subjects seropositive for adenovirus was required before CSF anti—HIV antibodies could be considered to be produced within the central nervous system. of the forty-one subjects tested eight were asymptomatic, eight were clinic— ally well but had significant lynphadenopathy, fourteen were immunodeficient and had constitutional synptcms (AIDS—related conplex or ARC) and eleven had AIDS. Oligoclonal banding was detected in the CSF of sixteen subjects and a pleocytosis was present in twenty-four. Neither finding clustered with a particular stage of infection. It appears that serological evidence of HIV infection of T lynphocytes and of the central nervous system occurs simultane- ously. All HIV infected subjects are at risk of developing prinary neuro- logical as well as immunological sequelae. Sindlarly, currently poorly under- stood resistance factors nust protect both lynphocytes and nervous system tissue frtnldanage by the HIV virus, as to date, the najority of infected subjects have not become innunodeficient or developed neurological disease. T'1E116 IMMUNOLOGICAL PARAMETERS IN HIV—INFECTED SPANIARDS:HIGH MONOCYTE NUM: BERS IN PERSISTENT LYMPHADENOPATHY PATIENTS. Arnaiz-Villena A, Alcaml J, Regueiro JR,. Inmunologia,Hospital Primero Octubre, 28041 MADRID. SPAIN. The paleo-North African origin of the Spanish population makes it an interesting eth nic group for the study of AIDS in Caucasians.We have thus established the immu— nological status of the different stages of HIV infection in Spaniards. One hun- dred HIV+ patients (as assessed by both Elisa and Western blot tests) were stu- died(81 drug addicts, 7 homosexual, 4 post-transfusional, 2 heterosexual transmi ssions,2 mother/child infected couples and 2 belonging to no obvious risk group) The following parameters were studiedzperipheral blood mononuclear leukocytes (PBML) subpopulations (CD3,CD4,CD8,CD11 and CD20),serum immunoglobulins, in vi- tro proliferative response to phytohaemaglutinin (PHA), anti-CD3 and pokeweed, EEG anti—HIV proteins (p15,24,31,41,53,55,64 and 120) serum IgG antibodies. CDC clasification criteria Were used:27 asymptomathic(AS),27 with persistent lympha- denopathy (LAP),26 with AIDS-related complex (RC) and 20 full—blown AIDS were ob served.RESULTS:all patients had high polyclonal serum IgG levels and high CD8+ PBML (p< 0.05) as compared to healthy controls.Intersstingly,LAP patients showed high monocyte numbers (510 25 331, p (0.05) and CD11 PBML (594 :5 282, p< 0.001) as compared to AS group, but both variables were back to normal values in RC and AIDS subsets; this may be pf value for assessment of illness progress,and,in LAP individuals, dropping CDll PBML may indicate a poor prognosis.Compared to AS and LAP groups,RC and AIDS patients had lymphopenia (p <0.001),low CD4 PBML (p<().001), low CD4/CD8 ratio (p< 0.001) and low lymphoproliferative responses (PHA,p< 0.001; anti—CD3,p (0.01). Lastly,compared to all other groups,AIDS pa— tients had high serum lgA levels (583 ya 250 mg/dl, p (0.001) and lower p15 (p (0.05) and p55+ (p (0.01) anti-HIV antibodies. The use of these variables for the diagnosis and prognosis of HIV-infected patients is discussed. THURSDAY, JUNE 4 THP117 The Existence of an Inhibitory Factor(s) against HIV-Reverse Trans- ' criptase in Sera from AIDS and ARC Patients. ROBERT J. PETRELLA, Y. SEI, M.M. YOKOYAMA, J.G. BEKESI, Mount Sinai School of Medicine, New York, New York 10029 USA We have investigated inhibiting and enhancing effects of HIV infected indi- viduals' sera on HIV-reverse transcriptase (RT) activity in vitro. The modula- ting effects were not observed in assays containing sera taken from HIV-unin- fected homosexuals and heterosexual controls, suggesting that the inhibitory and enhancing phenomena are associated with HIV infection. The presenting study has focused on the inhibitory function of the sera. h of 20 (20%) AIDS and 5 of 33 (15%) ARC patients sera showed the inhibitory effect. The effect was not observed in either 20 HIV(-) homosexuals or 28 heterosexual controls. Enzyme kinetic study showed that sera with the inhibitory property lowered the maximum velocity attainable with a given amount of enzyme (Vmax), but did not affect the dissociation constant for the enzyme with its RNA substrates. The result suggests the presence of one or more non-competitive inhibitory factor (s). Furthermore, the inhibitory function of sera was completely absent in the eluates of protein A-agarose affinity chromatography columns. These re- sults indicate that the inhibitory factor is probably an antibody that binds at a site on HIV-RT other than the RNA binding site. In addition, sera from AIDS subjects that displayed RT-inhibiting effects showed significantly greater neutralizing activity than non-inhibitory sera, implying that the inhibitory antibody may contribute partially to the sera's neutralizing activity against HIV infection. The existence of this inhibitor points out several diagnostic problems and therapeutic possibilities. THP_113 Defective T Cell Mediated Natural Anti—Bacterial Activity in HIV— Infected Patients GUIDO POLI*, L. NENCIONI**, M. ROMANO**, A. LAZZARIN***, A. MANTOVANI*, and A. lAGEIAEUE**, *Istituto M. Negri, Milano, Italy, **Centro Ricerche Sclavo, Siena, Italy, *** Istituto Malattie Infettive, Milano, Italy. Circulating mononuclear cells (PBM) of healthy subjects possess an in vitro natural activity (NA) against enteropathogenic bacteria, including Salmonella. The effector cell is characterized as a CD4(+)/CD8(—)/Leu8(+) T lymphocyte, acting against bacteria by an ADCC mechanism, via cytophilic IgA. Because AIDS is a profound immunodeficiency caused by human immunosuppressive virus (HIV) involving primarily CD4 lymphocytes, it was of interest to assess NA of HIV-infected subjects at various stage of disease. Results indicate that NA against Salmonella t hi is significantly decreased in AIDS as well as ARC and LAS patients. WortEy of note, CD4(+)/Leu8(+) lymphocytes were previously demonstrated to be the most susceptible subpopulation of T lymphocytes to HIV infection. Anti-S. t hi IgA levels were studied in HIV-infected population and in healthy suEJects. Despite an increased level of total IgA, AIDS and ARC patients show a profound depression of specific anti-S. typhi LPS IgA. Therefore, both the cellular and humoral components of anti-5a omonella NA are profoundly depressed. These data can provide an explanation for the increased incidence of bacterial infections in AIDS and ARC patients, including Salmonellosis. T}{E119 Randomized Clinical Trial of Plasma and Recombinant Hepatitis B Virus Vaccines in Gay Men N. Ddaka*, L. Eldred*, S. Cohn*, A. Munoz*, H. Fields**, F. Polk*, et al., *Johns Hopkins School of Hygiene and Public Health, Baltimore, MD, **Centers for Disease Control, Atlanta, GA. A randomized, double-blind comparative study of plasma (20ug/dcse) versus recombinant (10ng/dose) hepatitis B virus (HBV) vaccine (both provided by Merck Sharp and Dohme) was conducted in 186 gay men without serologic evi- dence of prior HBV infection. Vaccine was administered intramuscularly in the deltoid at 0,1, and 6 months; serum was obtained at 0,1,6 and 9 months and assayed for anti-HBs by radioimmunoassay. HIV serologic status was determined by EIA and immunoblot. Results among 158 who received all 3 doses and from whom 9-month serum was available were: Plasma Recombinant HIV neg. HIV go . HIV neg. HIV pos. Seroconversion 60/69 (.87) 2/8 (.25) 51/72 (.11) 1/9 (.17) (>20 mIU) ln anti-HBs level 0 0 0 0 0 1 mo. 0.46 0.09 0.38 0.01 6 mo. 3.09 1.34 2.43 0.67 9 mo. 4.11 1.63 3.48 0.99 Multivariate analysis of data from all 186 participants, with an autoregressive model, demonstrated that the plasma derived HBV vaccine was significantly more immunogenic than the recombinant vaccine, and that HIV infected men were significantly less likely to respond to either vaccine than were HIV seronegative men. 183 THB120 Cross—Reacting Neutralizing Antibodies Against Three Different strains of Human Immunodeficiency Virus (HIV). LUBA K. VUJCIC. D.H. SHEPP, AND G.V. QUINNAN. JR.. Division of Virology, OBRR, FDA. Bethesda, MD, USA The cross—reactivity of neutralizing antibodies against different strains of HIV is of interest with regard to potential vaccine efficacy. Sera from patients infected with HIV were tested against the IIIB, LAV. and RF-II strains of HIV for neutralizing antibodies. The IIIB and LAV strains are closely related, but both are distantly related to the RF—II strain. The methods used for this rapid microneutralization assay have been described previously. Briefly, sera and virus were incubated for 90 minutes followed by the addition of Holt—3 cells as the indicator cell line. Four to five days later neutralization was determined by a 50% reduction in giant cell formation. In this system giant cell formation correlates with other parameters of viral replication. To date 15 healthy asymptomatic patients and 8 patients with AIDS have been tested against all 3 strains of HIV. Of these sera, 86% neutralized the IIIB strain with a geometric mean titer (GMT) of 1:79 for the positive samples. 78% neutralized the LAV strain with 3 GMT of 1:75. and 59% neutralized the RF—II strain with a GHT of 1:17. The results obtained with the IIIB and LAV strains were 95% concordant. The results obtained with the RF—II strain were 68% concordant with those obtained with the other strains in terms of presence or absence of neutralizing antibodies. The results indicate that HIV often induces cross—reactive antibodies. It is unclear whether a vaccine based on antigens of a single strain would induce immunity protective against distant variants of HIV. THE121 Increased B-Cell Activation and Immaturity Associated with Human Immunodeficiency Virus (HIV) Infection W.“ E. CRABB*, R.T. MITSUYASU**, J.L. FAHEY*, AND J.V. GIORGI**, *Depts. Micro. & Immunol. and **Medicine, Jonsson Comp. Cancer Ctr., UCLA School Medicine, Los Angeles, CA 90024 The expression of phenotypic markers on B lymphocytes in patients with AIDS, in HIV-sero(+) individuals, and in healthy HIV-sero(-) donors was examined by two—color flow cytometry. Patients with AIDS and HIV-sero(+) individuals showed an elevated percentage of B cells (Leu 16+, CD20) bearing an activation marker, the transferrin receptor, when compared to donors not infected with HIV. A decrease in the percentage of resting (Leu 8+) 8 cells was also seen in AIDS patients and HIV-sero(+) individuals. An increased percentage of circulating, immature (CALLA-positive, CD10) B cells was seen in AIDS patients. These phenotypic changes were accompanied by an increased level of spontaneous IgG and IgM secretion, and increased cell size within the total B cell population, and within some B cell subpopulations, in patients with AIDS and in HIV-sero(+) subjects. These results demonstrate that phenotypic changes indicative of in vivo B cell activation and immaturity accompany the polyclonal production of Ig seen in HIV-infected individuals. This work was supported by NIH grants AI15332, AI52573, and CA00132, grant 86LA012 from the California Universitywide Task Force on AIDS, and funds from the will Rogers Memorial Fund. This work is based on work supported under a National Science Foundation Graduate Fellowship to E. Crabb. THE122 Human Imunodeficiency Virus (HIV) Antigen (Ag) and Antibody (Ab) Profiles in Children with HIV Infection: Correlation with Clinical Status. N. KAMANI", L.R. KRILov", an. email“, A.E. WITTEK**, and 0.3. QUINNAN**. *SUNY Stony Brook & Schneider Child Hosp of Long Island Jewish Med Ctr, Dept Peds, New Hyde Park, NY, **Div of Virology, FDA, Bethesda, MD. HIV Ag and Ab profiles were determined on sera from 25 children (160”, 93) with HIV infection. 6 children (ages 4-84mos; median 5mos) had CDC-defined AIDS with opportunistic infections (01); 2 children (ages 12 5 75mos) had his— tologically confirmed lymphoid interstitial pneumonitis (LIP); 17 children (ages 4-108 mos; median 39mos) had AIDS-related complex (ARC) with persistent generalized lymphadenopathy. HIV p24 Ag was detected in serum by enzyme immuno- assay. Western blot analysis of Ab responses to multiple HIV Ags revealed 3 patterns of response: (A) strong total IgG and IgGl responses to all viral Age including p24 and detectable IgA, IgM E/or Ing—A responses to multiple viral Age; (B) weak or absent IgG and 1301 response to p24 Ag with significant Ab responses to other Age; (C) weak or absent IgG and IgGl response to p24 Ag and at most minimal Ab response to other viral Age. Clinical status and Ag/Ab pro- files are tabulated below. Clinical Status 224 Ag Ab profile pattern ++ + NEG (A) (B) (C) AIDS with OI 2 3 1 l - 5 AIDS with LIP 2 — - - 1 1 ARC — 5 11 14 1 l The presence of Ag in the absence of a significant Ab response to p24 corre— lates with AIDS and a strong Ab response to p24 Ag plus detectable Ab to other HIV Age in multiple Ab subclasses correlates with a more stable clinical status. The longitudinal evaluation of Ag/Ab profiles may help in the assess- ment of clinical prognosis for children with HIV infection. THURSDAY, JUNE 4 TiiP123 Frequency and significance of serum monoclonal IgG at various stages ' of HIV-1 infection. D. EOUSCARY, R, FIOR, L. INTRATOR, C. PICARD, A. SOBEL. Département d'immunolo- gie, Faculté de médecine, Créteil 94010, France. A number of HIV—associated abnormalities, such as alteration of regulatory T—cell functions, viral reactivations, B-cell hyperreactivity and B-lymphomas, suggest the possible emergence of B cell derived monoclonality. Indeed, oligo- clonal bands have been occasionaly reported in patients with AIDS. A systematic investigation was realized in 150 consecutive patients with HIV-1 infection. Monoclonal immunoglobulins were detected by electrophoresis and immunofixation in agarose. A monoclonal IgG was found in 18 cases (12 Z). 20 Z of these had at least a second peak. Most of the peaks were IgG K (95 Z) and did not exceed 2 g/l. The patients with M—IgG (group I) were compared to the 132 patients withom M—IgG (group II), for a 4-15 months observation period. Both groupsdid not dif- fer in terms of clinical status (asymptomatic carriers, LAS, ARC or full-blown AIDS), above 70 Z of the individuals being in both former categories. M-IgG was not related to the presence of Kaposi sarcoma. Blood transmitted HIV (drugs u— sers and transfusions) were slightly more frequent in group I (72 Z vs. 42 Z)s Polyclonal hypergammaglobulinemia was more frequent in grOUp I (71 I vs. 44 Z). Mean lymphocyte counts, T4 (760 vs. 618), T8 (930 vs. 757) counts were compara— ble in both groups. Viral serologies were similarly distributed. During the ob- servation period the M—Igc persisted in 3 patients, disappeared twice. None of the 150 patients had lymphoma. These data confirmed the high frequency of M—ng even at early, poorly symptomatic stages of HIV-1 infection, when immune defi— ciency is likely to be limited. B-cell hyperreactivity was commonly associated without evidence of EBV reactivation. Nevertheless, this study supports the hy- pothesis that genetic rearrangements of B-cells occur early and frequently,pro- viding favorable conditions for a multistep process of lymphomagenesis. THR124 Alpha Interferon of a Marker and a Secondary Pathogenic Factor in AIDS BERNARD BIHARI, F. Drury, V. Ragone, G. Ottomnelli, E. Buimovici—Klein Several prospective studies of high risk groups have suggested that alpha interferon (alpha IFN) in an acid labile form, is a narker for the future devel— opnent of AIDS. In our low dose naltr one study reported elsewhere at this conference, the nean admission alpha I level was 160 i.u. Sixty percent of the patients showed a gradual sequential decline in alpha IFN levels, plateauing at 8 i.u. and 40% showed no such drop. The first group, called responders, had a nuch higher lZ—nDnth survival rate than the nonresponding group, (83% vs 19% p4:.Ol) and fewer najor O.I.'s (p<:.01). The results suggest that lowering the pathologically high levels of alpha IFN has a protective effect. Of interest was the finding of an inverse relationship between the adnission absolute nunber of T4's and the adnission alpha IFN level in the responder group (p<:.01) not exhibited in the nonresponder group. These results support the hypothesis that alpha TIN is an inportant nerker both for disease progression and for treatnent response. They also suggest that alpha IFN is a najor secondary pathogenic factor in the disease. This is supported by the experience with recombinant alpha IFN in aninal studies and in clinical trials with cancer patients, dennnstrating significant suppression of cellular innmnity, including TA nunber and function. In addition, alpha IFN acts in vivo as an opioid, and in high levels is likely to down regulate opiate receptors on innmnocytes and pituitary beta endorphin production, thereby disturbing endorphinergic cor— rection of innune systan dysfunction. THR125 Recombinant HIV fl Gene Products Induce Human Immune—Specific Lym hocyte Rasponigs In Vitro. ‘ 1 JOHN H. TORSETH , r.w. BERMAN , AND T. C. MERIGAN . Stanford University School of Medicine, Stanford, CA, Genentech, Inc., South San Francisco, CA Peripheral blood mononuclear cell cultures were established from 56 patients with antibody to human immunodeficiency Virus. Asymptomatically infected patients (7/ll) had significant immune responses induced in culture by an immunoaffinity purified, recombinant glycoprotein (gp—IBO) from the virus. In addition to stimulating the production of gamma interferon, this recombinant version of gp—iZO protein induced transformation responses which predicted clinical disease status as well as correlated directly with circulating levels of helper/inducer lymphocytes (r-O.43, p 0.01) and indirectly with virus antigen (p-0.025). Three of 27 patients with AIDS- related complex (ARC) also responded to this protein. However, these responses occurred significantly less frequently than responses to herpes simplex virus and cytomegalovirus antigens in the same seropositive patients. Neither this protein, nor two other immunorsactive, recombinant HIV proteins induced such in vitro responses in 11 seronegative subjects, thus the antigenic responses are immune—specific. Our findings suggest that HIVvspecific cellular immune responses to gp-130 decline in association with disease progression, and become undetectable in frank AIDS. In addition, they appear to serve as a marker for immune responses important in prevention of blood borne dissemination of free virus (as detected by serum HIV antigen assay). 184 THB126 Abnormal leukocyte functions in HIV—infected asymptomatic homosexual men with normal CD4+ T—cell numbers FRANK MIEDEMA, A.J.C. PETIT, F.G. TERPSTRA. J.K.M. EEFTINCK SCHATTENKERK*, F DE WOLFF**, P.Th.A. SCHELLEKENS et al., Central Lab. Netherl. Red Cross Blood Transfusion Service, incorporating the Lab. of Exp. and Clin. Immunology of the Univ. of Amsterdam, *Dept. of Internal Medicine of the Univ. of Amsterdam, **Municipal Health Service, Amsterdam, The Netherlands To investigate early effects of HIV infection on the immune system, we stud- ied leukocyte functions in HIV+ asymptomatic homosexual men (n-lh) classified in group II, compared to HIV- homosexual men (n-ZO). All HIV+ men, except one, had normal absolute CD4+ T—cell numbers, in 7 men CD8+ cells were elevated. CD20+ B cells were low in 5 HIV+ men, monocyte numbers were normal. Compared to HIV- homosexual men, the HIV+ men showed decreased T-cell proliferation in- duced by CD3 Mab in the presence of normal accessory cells. T-helper activity for polyclonally (PWM)-stimulated normal 3 cells was decreased in HIV+ but not in HIV— men. Accessory cell function of monocytes in CD3 Mab-induced prolifera— tion of purified normal T cells was decreased in HIV+ men compared to HIV- men. Immunoglobulin (Ig) synthesis in the PWM-driven system by B cells of HIV+ men was severely deficient and was not restored by addition of normal CD4+ T cells or depletion of CD8+ suppressor cells. In the microculture system (80,000 MNC/well) only MNC of HIV—homosexual men showed spontaneous Ig production. Both HIV- and HIV+ homosexual men showed a decreased abnormal in-vivo antibody response to immunization with Keyhole- limpet hemocyanin. Our results suggest that HIV induces immunological abnorma- lities before CD4+ T-cell depletion occurs. THR127 T8+Leu15' Cytotoxic Cells in AIDS-related Diseases in Hemophil'iac Patients ALAN P. KNUTSEN. J.D. BOUHASIN, J.H. JOIST, S.T. ROODMAN, St. Louis University Védica Center, St. Louis. MO, USA. The purpose of this study was to quantitate T cytotoxic cells in HIV sero- positive hemophiliac subjects and to correlate these to disease state. Defic- ient T cell cytotoxlcity to viral-infected target cells has been reported in patients with ARC and AIDS. Recently, Nicholson et al reported elevated num— ber of cytotoxic T cells in the blood of HIV-seropositive asymptomatic homo- sexual men. In our study, the percentage of T8 suppressor/cytotoxic cells were elevated in HIV-seropositive hemophiliacs who were asymptomatic (N=41), had ARC (N=6), or AIDS (N=7) compared to seronegative hemophiliacs (N=24), 44.9, 45.3, 51.8 vs 31.4% (P<0.01, <0.01, <0.01, respectively). However, the absolute number T8 cells were not statistically different among these groups of hemophiliacs. Phenotypic analysis of dual-labelled T8Leu15 cells revealed that seronegative hemophiliacs (N=7) compared to normal controls had increased percentage of T8+Leu15- cytotoxic cells, 94.2 vs 69% (P<0.01). Similarly, se— ropositive hemophillacs of all 3 groups had increased percentages of T8+Leu15' cells though not statistically different from sarnnegative hemophiliacs. Se- ropositive asymptomatic hemophiliacs (N=30), however, had increased number of T8+Leu15‘ cells gompared to seronegative hemophiliacs and controls, 704 vs 488 and 301 cells/mm (P<0.01, <0.01, respectively). Furthermore, T8+Leu15' cells were decreased in hemophiliacs with ARC (N=5), 531 cells/m3 (P=NS), and with AIDS (N=4), 259 cells/run3 (P<0.01). In sunmary, T8+Leu15' cytotoxic cells may be important in controll‘lng HIV infection, evident as an increase in our seropositive asymptomatic hemophiliacs. A decrease of T cytotoxic cells may have predisposed some to develop AIDS or be a reflection of disease activity. THR128 DIRECT DETECTION OF HTLV-III ANTIGENS 0N LYMPHOCYTES FROM PATIENTS WITH AIDS AND AIDS RELATED COMPLEX. Denis Burger, Mark Loveless, Patricia Watson Martin, Randy Hodges, Sue Caouette, Paul Yoshihara, and Andrew Goldstein, Epitope, Inc., Portland, OR 97006. Monoclonal antibodies were produced against HTLV-III, the etiologic agent of AIDS and ARC. One of these monoclonal antibodies, designated 3D8, was reactive with the viral core protein (gEgL by Western blot analysis against viral lysates and by ELISA assay versus cloned gag product. Antibody 3D8 was used to detect expression of HTLV—III antigens on the H9 cell line following viral infection as well as on lymphocytes from seropositive patients. Virally- infected H9 cells were found to be highly reactive with antibody 3D8 by FACS analysis. Forty-five Western Blot—positive patients representing AIDS, ARC and an asymptomatic group were studied using flow cytometry. A significant percentage of T4-positive lymphocytes from individual patients were stained with antibody 3D8. The highest percentage of HTLV—III positive cells came from patients with AIDS (up to 502 staining of T4 cells) although patients with ARC and patients without symptoms also demonstrated significant expression of HTLV-III antigens. Moreover, there was a correlation between the number of patients expressing HTLV-III antigens on T4 cells and clinical grouping. These data suggest that a higher percentage of TA-Iymphocytes express HTLV-III antigens than has been predicted by detection of intracellular HTLV-III mRNA. THURSDAY, JUNE 4 A IKNGITUDINAL STUDY IN HEALTHY INDIVIDUALS PHILIPPE C. BISHOP, D.C. BOQIE, J.W. PARKER, USC School of Medicine, Los Angeles, CA. The study was undertaken to assess the variations in the innunological phenotypes of peripheral blood lymphocytes and monocytes in repeated samples from five healthy volunteers who were not at risk for AIDS. Weekly sanples were obtained for 13 weeks. Monoclonal antibodies to seventeen lynphocyte and five mmcyte antigens were evaluated using two color flow cytometry. Individual and group mean (s.d.) differences were calculated from data for consecutive weeks to determine overall variation. Average week to week differences were less than 5% with the exception of 12+ (17.1%, s.d. 14.7), NKH+ (6.2%, s.d. 4.3), m1+ (9.8%, s.d. 6.6), and 102+ cells (7.2%, s.d. 5.4). During the course of the study, one subject had synptcms associated with a commn influenza-type viral infection and showed a tanporary reversal in the helper/suppressor ratio (0.82) which reverted back to normal (1.83) the following week. Overall, most of the phenotypes retained relatively constant with the exception of those associated with activated lynphocytes, natural killer cells, and nonocytes. The observed variations presumably reflected both technical inconsistencies and responses of the inn-me system to daily environmental stinuli. Because patients also undergo the same types of environmental insults, but may have a more labile irnmne system, serial phenotypic measurements are essential to adequately assess their inlmnological status. THR130 Uligoclonal IgG bands on Serum-electrophoresis in a Cohort of Homo- sexual Men in Stockholm, Sweden. GURAN BRATT, L WALDENLIND, G v KROGH, A KARLSSUN, L MOBERG, E SANDSTRDM. Dept. of Clinical Chemistry and Venhalsan, Dept. of Dermato-venereology, S'ddersjukhu- set, Stockholm, Sweden. As part of a health screening project for asymptomatic gay men in Stockholm, sera from 145 men collected 198} and 1984 were examined with agarose electropho— resis and immunofixation with 1913, 19A, 19M and kappa/lambda antisera (Dako- patts, Denmark). HIV-seropositive men were reexamined in 1985 and 1986. 1130 age matched healthy male blood donors served as controls. The results were as follows: HIV-serology 3 Individuals with oligoclonal bands, (198 level (9/1)) 1983 1984 1983 19811 1985 1986 NEG NEG 110 1 (11.2121) 0 (10312.1) — — NEG P05 10 2 (10.6 :1.0) 1 (11.41 11.9) 4 (13.6 I 2.1) 5(121 0 :15) P05 P05 25 14 (111.8 1 2.8)15 (15.4: 2.9) 11 (16.0 1 3.4)11 (16 3 1 L9) CONTROLS 100 o (11.5 _+_1.6) All the oligoclonal bands consisted of 198 with either kappa or lambda light chains. During the 3 year follow—up 3 of the 25 men, who were HIV—positive in 1983, developed AIDS. All had oligoclonal bands and 1913 levels >15.4 g/l in 1983. Dligoclonal bands seem to be a common finding that parallel high lgG levels in HIV-positive gay men. It is not an early finding after seroconversion. Over 5 9.4 of the men who were HIV-positive in 1983 had oligoclonal 1913 bands and this finding seemed to be constant over the follow—up period. T|{R131 Antibody Response to a Recombinant Hepatitis B Vaccine in Anti-HIV Positive vs. Anti-HIV Negative Persons MICHAEL GESEMANN*, N. BROCKMEYER**, N. SCHEIERMANN*, E. KREUZFELDER*, A. snrrrvrss, E. SIMOEN***, et al., *Institut fur Medizinische Virologie und Immunologie, Universitatsklinikum, Essen, FR Germany. **Dermatologische Klinik, Universitatsklinikum, Essen, FR Germany, ***SmithK1ine-RIT, Rixensart, Belgium. To determine the influence of HIV (Human Immunodeficiency Virus) infection on the outcome of hepatitis B vaccination, 19 homosexuals seronegative (group I) and 8 persons anti-HIV positive (group II) were vaccinated with 20 mcg doses of a yeast-derived hepatitis B vaccine (SmithKline-RIT, Belgium) at months 0, l, and 6. Another 12 anti-HIV positive persons (group III) with evidence of past exposure to HBV (Hepatitis B Virus) (anti-HBc positive, HBsAg negative; RIA, Abbott) also received a full course of vaccination. Anti-HBs (RlA, Abbott) levels were measured at months 0, 1, 2, 6, and 7. By month 7, 89 % of group I, but only 3 of 8 anti-HIV positive vaccinees (group II) had seroconverted (p=.005; Chi square test). Increases of anti-HBs levels from month 6 to month 7 averaged 230fold in group I (n=10) but only by factor 8 in groups 11 (n=2) and III (n=10) (p=.002;/Ni1coxon, Mann and Whitney rank sum test). Total and T4 lymphocyte counts determined at least once during the course of study were significantly higher in anti-HIV negative than in anti-HIV positive vaccinees (mean t std. dev.; total Iymphocytes:/2926 t 918 vs. 1562 t 736, p=.002; T4: 1048 t 413 vs. 398 t 206, p=.002; respectively). These data show that this yeast-derived hepatitis B vaccine is immunogenic in population at risk for acquiring HBV and HIV infection, but immune responses as measured by anti-HBs production are impaired in parallel to the decrease of T4 lymphocytes in the course of HIV infection. 185 THR132 Lymphocyte circadian cycles in HIV infected individuals: abnormalities of both CD4 and C08 cells. ’,C, DOINEL’*,J.Y. MULLER',CH.$ALI10N' ' CNTS-Instltui. *INSERM. Paris, Franco. Physiological circadian variations are observed In peripheral blood lymphocytes counts. The nadir occurs around 8.00 am. and the peak value at mimlght. ln HIV Infected Individuals, lymphocyte function abnormalities are frequent, So, we developed a prolwol to search for modifications in the CD4 and 008 Iymphowie cycles. Peripheral blood samples were obtained from 9 healthy controls and 16 HIV Infected patients : 9 were mmptomalic or lymphadenopathic seroposilive pallents (CDC group II-IIl), 7 were ARC or AIDS palients (CDC group IV), CDZ-OKTI I,CD4-0KT4 and CD8-0K18 cells were determined using fluorescein labelled monoclonal antibodies and a flow cyiomeler (Spectrum III wllh a 2 I 40 analyzer, Ortho Diagnostic Systems). Samples were oblained at 8.00 am. 4.00 pm, and midnight Using absolute number of cells, results were expressed In terms of a "hyclhemeral rallo"( NR) Le. mianghi count : 8.00 cm, count In controls. variations were noted for all lymphocyte subpopulallons ; CD4-NR wasl.6:0.4 and CD8- NR l.4:0.2. In CDC woup IV patients, cycles were always Impaired : CD4-NR were less than H and CDB-NR lesclhan I. In lhe9CDC group II - Ill patients, 5 had cycles comprised In the normal range. 4 had both CD4-NR and CDB-NR decreased. It is of Interest that there Is no correlation between the absolute number of any lymphocyte subset and any NR value. So, CD4 lymphocyte cycle abnormalities were observed even in patients with normal CD4 absolute count Furthermore, even for CD8 cells (that are not Infected by HIV) NR values were low. Independently of their absolute count Because all CDC group IV patients had lymphocyte cycles abnormaliiles, the evaluation of NR might become an early progmsls factor. This would be of great interest to CDC II—III group In keeping wIih their nyclhemcral cycles. THR133 Zinc Deficiency and Human Immunodeficiency Virus Infection. JULIAN FALUTZ, C. TSOUKAS, J. WOLSKA, J. SAMPALIS, P. GOLD. McGill Univemal, Quebec, Canada. The role of co—factors, including malnutrition, in the observed immuno- suppression associated with the human immunodeficiency virus infection (HIV) is unknown. Zinc deficiency predisposes to reversible abnormalities of cell- mediated immunity, as well as thymic atrophy and dysfunction. To assess the possible role of low zinc as a co-factor in the severe immunosuppression characteristic of advanced HIV disease, we measured serum zinc, albumin, and T cell numbers in CDC determined subgroups of HIV infected individuals. Zinc was measured by atomic absorption spectrophotometry. T cell subsets were measured by monoclonal antibodies. Comparisons were for groups versus controls. Results are expressed as mean t 3.0. Control Group II Group III Group IVA Group IVC1_ Group IVD n = 22 7 19 5 14 6 Zinc meg/d1 1.17:0.2 1.32:0.3 1.05:0.1c 0.96:0.1c 0.79:0.2e 0.92:0.1d r helpers Imma 9351376 53112264“ 6752330b 289:317d aotaod 104:128d Albumin g/dl 5.12:0.3 4.520.533 4.9:0.5a 4.310.613 3.820.6e A.2:0.6b '1‘ Test a=p<0.05 b=p<0.01 c=p<0.005 d=p<0.001 e=p<0.0001 Group IV patients had significantly decreased zinc levels, which correlated with the decline in immune status, as assessed by T helper cell numbers (r-0.43, p<0.002) Albumin was significantly decreased in all Group IV pa— tients. The etiology of the decrease in zinc with progressive HIV disease is likely mltifactorial. We hypothesize that low zinc may exert an addition— al immunosuppressive effect in HIV disease, and that zinc repletion may have a beneficial role in retarding an otherwise progressive decline in impunity. THP134 Human Monocyte Cytotoxicity for Candida Albicans Can Be Augmented ' with Gamma Interferon and MuramyI TrIpeptIde. Phillip D. SMITH, R.A. CALDERONE, L.M. "Al-IL and S.M. WAHL. NIDR, NIH, Bethesda, MD 20892 and Dept. of Microbiology, Georgetown University, Washington, DC 20007. Candida albicans (CA) is an opportunistic fungus commonly found in the oral cavity and esophagus of AIDS patients. Monocytes, which may exhibit impaired functional activities in AIDS patients, contribute to host defense against E. To explore possible mechanisms for augmenting monocyte antifungal activity, we developed a new microassay for measuring cytotoxicity of CA. Monocytes, purified by countercurrent centrifugal elutriation, were cocultured for 4 hr at varying effector to target (EzT) ratios with pulse—labeled (38—leucine) CA yeast cells (strain 4918). Increasing the E:T ratio correlated directly with— increased all release and inhibition of g. colony formation. Inhibitors of oxidative metabolism, myeloperoxidase, and phagocytosis caused a marked reduction in monocyte cytotoxicity for C_A, confirming in our assay that killing of Q was dependent upon reactive oxygen {intermediates and phagocytosis. In experiments designed to determine whether this cytotoxic activity could be augmented, we found that recombinant gamma interferon or muramyl tripeptide (delivered in liposomes) alone did not increase monocyte cytotoxicity for CA but acted synergistically to augment cytotoxicity several-fold. _ Thus, the ability to enhance monocyte antifungal activity of g may have clinical relevance for immunocompromised hosts, in particular AIDS patients with E and other fungal infections. THURSDAY, JUNE 4 THB135 The Generation of Natural Killer and Lymphokine Activated Killer Cells in HIV—Infected Individuals. JAMES REUBEN, A. RIOS, G. BREWTON, AND P.W.A. MANSELL. ".0. Anderson Hospital and Tumor Institute, Houston, TX., U.S.A. Individuals infected with HIV usually lack natural killer (NK) cell activity; however, NK activity can be restored in vitro by the addition of interleukin-2 (IL~2). The addition of IL—2 also gives rise to another effector , the lymphokine—activited killer (LAK) cell. We investigated the ability of IL—2 to restore NK as well as to generate LAK activity in 15 patients with AIDS-related symptom complex (ARC) or lymphadenopathy syndrome (LAS) and 8 controls. Freshly isolated peripheral blood lymphocytes (PBL) were assayed for NK against the target, K562, and for LAK against the NK-resistant, Daudi cell line. In addition, PBL were incubated in vitro for 3 days with 50 units of recombinant IL—2 (rIL—Z, Cetus Corporation), harvested and assayed for NR and LAK activity. The results show that freshly isolated PBL from patients lacked NK when compared to control (4.8% vs 25.2%, respectively; p<0.01). NK activity was augmented by rIL—Z in all patients and controls; rIL—Z generated LAK in all cases but one patient. There was a high degree of correlation (r-0.91) between the increment in NK by rIL—2 and the generation of LAK. These data suggest that the same cell may mediate NK and LAK following incubation with rIL-Z. Studies are in progress to explore the generation of NR and LAK by HIV antigens as well as to investigate their effectiveness in the lysis of HIV—infected targets. THE136 A study of some immunological parameters in relation to HIV anti— genemia in patients infected by HIV P.5CHELLEKENS**, M.ROOS*, J.EEFTINCK SCHATTENKERK**. J.LANGE**, F.MIEDEMA*°; AND F. DE WOLF**, *Central Lab. Nether1.Red Cross Blood Transf.Service. in- corporating the Lab. of Exp. and Clin. Immunology of the Univ. of Amsterdam, **Dept. of Internal Medicine of the Univ. of Amsterdam, Amsterdam, The Netherlands The relation between infection with HIV and various immunological parameters was studied in the following groups of individuals: a) healthy controls; b) homosexual individuals from the AIDS risk group without anti-HIV antibodies; c) idem, but with anti—HIV antibodies; d) patients with lymphadenopathy syn- drome; e) patients with ARC; f) patients with AIDS and opportunistic infec- tions. Each group, consisting of 15—20 individuals was tested for: absolute numbers of TA- and T8-positive cells; ratio T4/T8; and cellular immunity both in vivo and in vitro. Healthy HIV—antibody positive individuals and patients with LAS showed aready a decreased ratio TA/TB, mainly due to an increase in the number of TB-positive cells. The ratio in ARC and LAS was even lower but now due to low numbers of T4+ cells and with normal numbers of T8+ cells. The lymphocyte proliferative response, low in the HIV-antibody positive group. was normal in the LAS group but profoundly decreased in the ARC and AIDS group. In the HIV-antibody positive group the severity of the impairment of the various parameters of immunocompetence was not related to the presence of antigenemia. Compared to healthy controls the antibody response after immunization with KLH was depressed (although not absent) in all groups studied. Prevalence of HIV among the Infectable Drug Using Population in South London and Factors Influencing its Spread. THP.137 G WEBB“, M BURGESS*, S SUTHERLAND", J STRANG‘, T J MCMANUS‘ *King's College Hospital, London, ** Public Health Laboratory Service This study surveys the HIV antibody status of 250 infectable drug abusers in South London and includes a more detailed analysis of 100 of those tested. evolved from a clinically perceived need to identify rapidly common risk factors when HIV antibody testing to include in local health education cam- paigns. The subjects are a mixed sample comprising those who are or were involved with various agencies and those still on the street. It The overall study also looks at the general drug taking behaviour of the sub- jects, with particular reference to their injecting and sharing habits, together with other facts which could influence or facilitate the transmission of the virus within the population. The more detailed survey focuses on past and continuing drug abuse and its associated behaviour, together with an analysis of changing sexual behaviour and behavioural modification linked to the awareness of the virus and its differing modes of transmission. This gives insight in the way the virus has passed from particular at risk communities to the more general non-drug abus- ing population. The surveys are being conducted over an 18 month period. They demonstrate a five—fold increase of HIV infection in this previously HIV-free population, over the first 12 months of the study alone. Revised figures will be included in the survey in time for the Conference. 186 THR138 Financial Analysis of AIDS Programs in the Americas DONALD S. SHEPARD*, Y. KOURI*, F. ZACARIAS**, C. CAMERON*, P. ROSE— LLO',"L.G.M.RODRIGUES , et al,. -Harvard Institute For International Develop— ment, Cambridge,MA, **PAHO, Washington, D.C.,'Health Departnent, San Juan,PR, " Ministry of Health, Brazil PAHO and WHO expect to receive approximately $200 million in fiscal year 1988 for AIDS control in developing countries. To be able to make and evaluate finag cial commitnents of such funds there is need to develop a financial system with national program and activities components. The national system compiles the 15 vel and uses of funds by year for all activities in the country, while activi- ties monitoring systems compile these data for individual program activities, and relates funding to outputs. For the national system a matrix reporting sys- tem is proposed for each year with sources (international and domestic agencies) and uses of funds (types of AIDS program activities such as case finding, con— tact tracing, screening, treatnent, education, and research). The activities monitoring system relates expenditures to the country's reporting system on the magnitude and trend of the AIDS problem in the country (cases diagnosed and num ber of deaths) and to specific indicators (e.g. number of repeatedly positive serological tests). A preliminary application to San Juan, Puerto Rico and Sao Paolo, Brazil, suggests that AIDS case management and treatnent is being financed primarily from general operating expenses of public hospitals, with the likelihood of re- ducing funds for all other treatnents. This framework is proposed as a tool for donors and national and state go— vernments to monitor uses of funds, target requests to needed areas, and cons- tantly improve the productivity of their expenditures. 1112139 HIV Infected African Patients With a Negative HIV ELISA Serology? ROBM L. OOLEBUNDEIS", H. FRANCIS“, M. IXJMA", T. WINN", G. VAN DER GROEN**i, F. PI5T***, et a1., * Projet SIDA, Kinshasa, Zaire, 3* NIH' Bethesda *** Institute of Tropical hbdicine, Antwerp, Belgium. In both healthy carriers and AIDS patients commercially available ELISA kits will not detect all Western blot(o) persons. Sera of all HIV(-) (Organon Teknika) patients with persistent diarrhea (n-ZS), a history of herpes zoster (n=15), a generalized pruritic papular eruption (n-9) or a generalized aggressive Kaposi's sarcoma (n-l), observed at Mama Yemo Hospital, Kinshasa, between June 1985 to October 1986, were tested by Western blot. The sera of 10 (20%) of the 50 HIV ELISA(-) patients with AIDS-like symptoms or signs had at least the protein band p 24 on Western blot (Du Pont strips). In 2 (4%) of these 50 patients, Western blots showed the presence of at least the p 24 and the gp 41 band. In one ELISA and Western blot(-) patient with persistent diarrhea, esophageal candidiasis was found endoscopically. In the 3 HIV ELISA(-) patients in whom cultures were performed, HIV was isolated. The sets of two of these patients were Western blot(-) and in the other, only a p 24 protein band was present. Antibody tests using other ELISA methods, LAV II and HTLV IV serologies are pending. Performance of Western blot tests should be considered when evaluating suspected HIV(-) cases of AIDS. Furthermore patients may be HIV virus carriers without the presence of HIV antibodies detectable by either ELISA or Western blot. \ THP140 The Effect of Pregnancy on Progression of HIV Related Disease. I ELLIE E. SCHOENBAUM*, PA SELWYN*, AR FEINGOLD*, K DAVENNY*, V ROBERTSON*, M ROGERS**, et. a1., *Montefiore Medical Center, *Albert Einstein College of Medicine, Bronx, N.Y. and **CDC, Atlanta, GA., U.S.A. It has been suggested that pregnancy adversely affects the outcome of HIV in- fection due to the physiologic immunosuppression that occurs late in pregnancy. We are prospectively studying the effect of pregnancy on the natural history of HIV infection in intravenous drug abusers attending a NYC methadone program. Women of child bearing age without AIDS or oral thrush(0T) are serially tested for HIV antibody(Ab), T-cell analyses and viral culture. Physical examinations and standardized interviews are performed. Pregnancy is identified early by routine monthly urine testing. Seropositive(SP) women delivering livebirths or carrying 724 weeks are compared to women who did not become pregnant or who terminated pregnancy by 13 weeks gestation. Of 276 women tested since July 1985, 96(382) were SP. Of these. 34 have been rescreened over a mean 12 mos. of follow—up. Among the rescreened, 15 (Group’l) had pregnancies carried ’24 weeks and were followed a mean of 6 mos. post-partum and 19 (Group II) either did not become pregnant (lb) or had pregnancies ter- minated by 13 weeks gestation (5). The two groups were stratified by the ab— sence or presence of generalized lymphadenopathy (GL) initially and followed for progression to CL, GT, or AIDS. Group Baseline Status No. Subjects No. Progresaed Mean Mos. F/U I without CL 12 6/12 GL only* 11 with GL 3 1/3 0T** 10 II without GL 7 2/7 GL only* 15 with CL 12 2/12 OT** 12 *p>.05 **p >.05 No subject developed AIDS, although 7/1S(47Z) in Group I vs. h/19(21Z) in Group II advanced in their HIV status (OR-3.3, p<.07). These preliminary data suggest that pregnancy was not associated with the occurrence of AIDS. Further study may confirm the trend of greater HIV disease progressiondue topregnancy. THURSDAY, JUNE 4 THP141 Pancreatic Disturbances and AIDS : an Anatomopathological Study ' FRAMIOIS BRICAIRE. C. MARCl-IB, D. 2011131, B. REGNIER, AG. SAIMUI‘. JM. DBCAZES. Hdpital Claude Bernard, Paris, France. A systematic analysis from autopsy of 113 AIDS patients has enabled us to confirm the existence of alterations of the pancreatic gland in about half of then. The cases studied were 99 men and 14 women whose average age was 36.8 years (22-71). Among them were 82 homosexuals. 25 Africans or Haitians. 3 drug abusers. l transfused patient. 2 without risk factors. An average of 12.4 montln elapsed between the discovery of the disease and death. Sixty seven patients had had isolated opportunistic infections. 7 a isolated Kaposi sarcoma of lym- phoma. and 39 had had both. Macroscopically the pancreas was normal in 59 cases : 54 patients showed alterations of the gland such as oedema and increase of volume (40). fibrous aspect (5), cytosteatonecrosis lesions (8), kaposian of lymphomatosis aspect (5). Histopathology revealed that in 16 cases the pan- creas could not be interpreted because of necrosis, alterations were found in 49 cases. aspects was normal in the remaining 49 cases. The main alterations were largely disseminated. The forms were cytosteatonecrosis (8) or subacute pancreatic disorder with inflammatory lesions (oedema. polymorphic granuloma) (33). fibrosis (14), metaplasia and dedifferentiation of the ducts (14) or vas- cular lesions (haemorrhage. thrombosis) (8). Specific lesions were observed in 21 cases. though non could be found in 28 cases. Such lesions. disseminated both in the exocrine and endocrine tissues and in the interstitial and ducti< cal ones, were as follows : cytcrnegalic inclusion cells testifying to CMV in- fection (10), cryptococcal (2). tuberculous lesions (1), kaposian sarcoma or lymphoma (8). In 19 cases specific lesions demonstrated were correlated to the clinical findings. The pathological processes observed histologically can be regarded as artial- 1y responsible for the disorders of the diystive system characteristic of IDS. THP142 The l-Iumoral Immune Response in HIV-Associated Periodonn'tis. EA. ' W.G. Grieve, J.R. Winkler. Univ. of California, San Francisco, CA, USA. We have recently observed an acute, painful and rapidly progressive periodontitis in HIV- infected individuals, which we have termed AIDS-virus associated periodontitis (AVAP). Little is known about the etiology and pathogenesis of this infection. The purpose of this investigation was to vide insight into the oral microbioata associated with the lesion. Since direct culturing of e associated flora is time consuming, expensive. and complicated, we chose to evaluate the systemic immune response to potential pathogens of AVAP. For this prupose we studied the immune response to the following potential periodontal pathogens: ’ ' ' ' ' and . An indirect ELISA assay was used to measure the level of antibody (Ab) in HIV-seropositive homosexuals, HIV-seronegative homosexuals and HIV-seronegative heterosexuals. Formalinized, whole bacteria were used as antigen in wells of polystyrene microtiter plates. After blocking unbound antigen sites, serial dilutions of serum were incubated, washed and blocked. The secondary Ab was Mouse Anti-Human IgG [Fc] Fragment, and the tertiary Ab was alkaline phosphatase conjugated Goat Anti-Mouse IgG F(ab')2. Substrate was added and measurements taken at OD405. A reciprocal dilution of serum required to provide a reading of 0.4 at OD405 was calculated for each patient Means with smdard deviations were then calculated for each group tested, and a t—test was applied to determine si ificance. Results for ‘ ' ‘ indicawd a significantly higher antibody titer for HIV-positive homosexuals than for HIV-negative homosexuals (p<.05), and heterosexuals (p<.001). For the same groups of people, results for . 1 indicated a higher titer, p<0.005 and p<.01 respectively. Interestingly, the results indicated no significant difference between the same groups of individuals for i W i ' V ' ' ' 'vi h v 'n ' ' ' V Supported by NIH Grant T35DEO7103. THP143 gzrgsyl Viglgt; A Rapid and Sensitive Stain for Diagnosing Engumogysgig ' ggrinii Pneumonia by Sputum Examination. C L M A D.A. EVANS, J. STEIN-STREILEIN, P. GANJEI, A. E. PITCHENIK, University of Miami School of Medicine, Miami, FL. The detection of P. carim‘i cysts in the sputum of patients with the Acquired Immuno- deficiency Syndrome (AIDS) has been useful in diagnosing P. carinii pneumonia noninvasive- ly. Gomori Methenamine Silver (GMS) has the advantage of staining the characteristic cyst (which is the most commonly recognized form). However, it is time consuming, technically involved and may be relatively insensitive for detecting small numbers of cysts in sputum. One hundred and ten expectorated sputum samples were collected consecutively from 90 patients with AIDS and unexplained pulmonary infiltrates. Each specimen was cytocentri- fuged onto two slides. One slide was stained with GMS and the other with Cresyl Violet (CV). All slides were read by two independent observers in a double blind fashion. Of 110 specimens, 27 (25%) were positive for P. carinii cysts by CVI and l7 (l6%) were positive by GMS. In 6 of the 10 patients whose sputa were positive by CV, but negative by GMS, P. carim'i was confirmed (by histology in 5 patients and by a typical clinical picture with response to specific therapy in 1 patient). In 4 of the 10 patients, 3 had no follow- up and one had no clinical evidence of P. carinii pneumonia. These results suggest that CV is more sensitive and as specific as GMS in detecting P. carinii cysts in sputum. CV staining of sputum is technically simple and takes only 30 min. to perform, while GMS is technically more difficult and takes 3 hrs. to perform. Since CV stains the easily recognized P. carinii cyst form (and not the much smaller trophozoite), it requires less special expertise than other rapid staining techniques for P. carinii (i.e. Giemsa stain). CV may be a superior stain for diagnosing P. carinii pneumonia by sputum examination. In patients with AIDS it could be easily adapted for general use to expedite diagnosis and treatment. 187 THR144 Combination chemotherapy (low dose- adriamycin,bleomycin,vincristine) for advanced Epidemic Kaposi's Sarcoma (EKS). PARKASH S. GILL,MARK U. RARICK, MARK KRAILO, CARMEN LOUREIRO, MARGORIE BERNSTEIN—SINGER, ALEXANDRA LEVINE et a1, University of Southern California School Med, Los Angeles, Calif. Thirty homosexual men with advanced EKS were treated with combination chemotherapy consisting of adriamycin, 10 mg/m2 (n=14), or 20 mg/m2 (n-lé). plus vincristine, 1.4 mg/mZ and bleomycin, 10 mg/m2,given IV every two weeks. At study entry, extensive cutaneous EKS involvement was present in 29, in whom 19 had associated lymphoedema; mucous membrane involvement was present in 17, symptomatic gastrointestinal disease in 5, lung involvement in 12. Systemic "B" symptoms were present in 17, and hx of past pneumocystis carinii pneumonia in 5. A: study entry, mean hemoglobin (Hb) was 12.7 gm/dl(r=9-22); mean absol- ute neutrophil count was 2886/d1 (r=1073-6724); mean lymphocytes were 1329 (r=377—3190), mean T4=146d1 (r-10-412); mean T4:T8 =O.2 (r=0.03—0.8). Chemo- therapy was begun at a median of 4 mos from initial dx (range=0-10 mos). Res- ponse rate was 78.6Z,with complete response in 14%, partial response in 662. An additional 18% had minimal response, while one patient had no response, and two are too early to evaluate. Poor prognostic indicators for survival include current or past hx of diarrhea (p=.03) and "B" symptoms (p=.02). Involvement of any particular visceral organ had no impact on response rates or survival. Toxicity included nadir mean Hb of 11.4 gm/dl, neutrophils of 1589/dl (324— 5530), opportunistic infections in 7 pts. Median survival was 8 mos. Because of these early results in pts with extremely advanced disease, we have begun a prospective, randomized trial of adriamycin alone (20 mg/m2) vs. ABV. Results will be presented. We conclude: (1) Low dose adriamycin, plus vincristine and bleomycin may induce remissions in 792 of pts with advanced EKS. (2) In spite of good responses, survival may be short, often due to other complications of AIDS. THP.145 KEITH KRASINSKL W. BORKOWSKY, S. BONK, R. LAWRENCE, AND S. CHANDWANL New York University-Bellevue Hogaital Center, New York, NY HIV infection in children is frequently complicated by bacterial infection, and preventive im munoglobulin (1G) therapy has been suggested. In a 3.5 year period we have cared for 70 HIV infected children (only 3 of which were treated with IG); 44 of whom had at least one bacterial culture. There were 1163 cultures performed in these 44 patients: mean = 26.5, median = 15, range 1—126 cultures per patient. There were 97 documented episodes of bacterialinfection in 26/44 (59%) of these patients (mean = 3.7, median = 2, range 1- 11). Otitis media, pneumonia, urinary tract infections and diarrhea were the predominant syndromes identified. There were 31 bacteremias among 17 patients (mean = 1.8, median = 2, range 1—5). Pneumooocci. were the most: com mon blood isolata (11/31), and types 4,6,9,“ and 19 were recovered. One patient had 3 separate episodes due no the type 6 organism. Other organisms included: 2. aeruginosa 2, E. cloacae 2, 5. meumoniae 2, s. aurets 2, g. viridans 2, enteroooocus 2; and one each of Streptococcus group A and B, s. 'erm‘ gm hilia Egg. calooaoeficgg. whamm,m diptheroids. One patient had concurrent E. cloacae and enbemooocal bacteremia. Overall 26/70 (37%) of patients with recognized HIV infection have had bacterial infection and 17/70 (24%) have had bacteremia, allof which were mutated with infection at other body sites. One of our 3 IG treated patients developed Klebsiella sepsis. Bacberialinfection could be implicated in the deaths of only 4 patients: 1 Wlth enberoooocaland varicella pneumonia, 1 with E. cloacae, fungaland CMV pneumonia, 1 with Pseudomonas and PCP, and 1 with pneumonia due to Pseudomonas only. Although bacterial infections are a frequent cause of morbidity in HIV infected children, they are usually treatable. IG therapy might have been expected to prevent the pneum infections, its' role in preventing other bacterialinfecfionsisles clear. Bacberial Infections In Human Im mmndeficiengy Virus (HIV) Infected Children. THP146 Neuropsycholog'lcal Characterization of HIV Infection. PIM BROUHERS*,M.C. HOBAN**. K. SQUILLACE“, R.T.JOFFE**, D.R. RUBINOW", ‘Georgetown University, MNational Institute of Mental Health, Washington, DC, USA. Reports that the brain may be directly and selectively affected by HIV infection has increased the importance of neuropsychological characterization of AIDS dementia in patients without opportunistic infections of the brain. He previously observed significant differences in the performance of a group of 13 patients with AIDS but without CNS opportunistic infection compared with 10 age and education matched homosexual volunteers on neuropsychological tests sensitive to alterations in attention and activation. In addition differences were found on tests measuring functions that are normally considered most resistant to global brain insult such as the vocabulary subtest of the verbal IQ. While no significant differences between the groups were found on tests assessing memory, both groups performed poorly on tests of verbal memory, scoring significantly below established norms. Similar findings have been observed in an additional 12 AIDS patients compared with 8 seropositive-only patients and 8 patients with chronic active hepatitis. These results suggest a two factorial component to the neuropsychological profile of AIDS patients, one component associated with attention and motivation, another with knowledge functions. The results additionally suggest that brain areas subserving language related functions may be selectively affected by the HIV infection, with the degree of impairment perhaps reflecting the status of the infection. Comparison of AIDS patients with Huntington's and Alzheimer's patients will be made to evaluate similarities and differences in their dementias. THURSDAY, JUNE 4 THP_14'] Assessment of Potential Chemotherapeutic Agents Against Mycobacterium avium Complex Infections in Beige Mice PATTISAPU K3. GANGADHARAM‘, V.K. PERUMAL, N.R. PODAPATI, K. PARIKH, M.D. ISEMAN, National Jewish Center for Immunology and Respiratory Medicine, Denver, Colorado M cobacterium avium complex (MAC) organisms are major opportunistic pathogens afflicting AIDS patients. Using the beige mouse model, we have investigated the chemotherapeutic potential of 20 compounds which showed high Q vitro antimycobacterial activity against numerous strains of MAC. The i_n yilg chemotherapeutic activity of each of these compounds was assessed in beige mice challenged intravenously with a virulent MAC strain, in each of 2 or 3 experiments. Comparison of the mortality and CFU counts of organisms from spleens and lungs at various periods of challenge between the drug-treated and control groups, enabled us to classify these 20 compounds into three groups: active, probably active and inactive. Activity i_n up was defined as a statistically significant reduction in the mortality and CFU counts of the organisms recovered in the drug treated group as compared with the controls; inactivity was defined as having no evidence of any difference at any point between these two groups. Drugs in the probably active group indicated some activity after prolonged chemotherapy, suggesting that perhaps with higher doses, these drugs would show more significant activity. By this classification, 4 drugs, amikacin, CQQ (gangamicin), clofazimine and rifabutin were classified as active; desoxyfructoserotonin and cyclopentyl rifampin as probably active; and the remaining 14 as inactive. These studies were extended to combination chemotherapy among these 4 active drugs. (Supported by NIH Contract No. 42544). Preliminary observations of the effect of cow's milk globulin upon intestinal cryptosporidiosis in AIDS. W L W, St. Luke's-Roosevelt Hospital Center, Columbia University, New York, NY Many of the intestinal (GI) complications of AIDS result from immune deficiency in the gut. Impaired secretory immunity in AIDS (Dig Dis Sci 32:129,1987) could affect the clearance of parasites from the GI tract. In this report, the preliminary observations of the effect of cow's milk immune globulin (stolle Research and Development Co) upon the course of chronic intestinal cryptosporidiosis in AIDS is presented. The globulin was prepared from the milk of cows that had been hyperimmunized with human enteric bacterial antigens (but not cryptosporidium) using a proprietary, slow release vaccine. The milk was pasteurized at low temperature under reduced pressure to prevent protein denaturation, then was passed through a membrane to retard molecules greater than 100,000 MW and concentrated 30 fold. Three patients were treated. All had diarrhea with cryptosporidia in stool samples and on intestinal biopsy. Patients were treated with ascending doses of the globulin given orally qid, with NaHCO . All 3 responded favorably, with the reappearance of some or all formed stools. Stool examinations reverted to negative in 2 patients tested and organisms disappeared from intestinal biopsies in l of 2 tested. While preliminary, the results strongly suggest that a large molecular weight fraction in cow's milk effectively suppresses cryptosporidiosis in patients with AIDS. THP.148 "13149 mmm IN THE morc‘ATIm or SALMONELLA IWEXII'IQE IN AIDS PATIENI'S. Dennis M. m, P.N.R. Heseltine, M.A. Appleman and $1.14. Leedom. University of Southern California, Los Angeles, CA, USA. Recurrmt episodes of salmonellosis, including recurrent life-threatening bacteremias, have been wel l-described in patients with AIDS. Because of the need to avoid sensitization to trjmethoprinVsulfamethoxazole (IMP/SEX) in AIDS patients and the high frequency of anpicillin resistance of salmonella iso- lates, alternative therapies rust be sought. We report the treatment of three AIDS patients, who had recurrent salmonellosis, with norfloxacin, a new oral fluoroguinolone which has excellait in 1119 activity against m sp. Each patient had 2-3 prior distinct clincal episodes of salmonellosis which had failed to be eradicated with standard courses of ampicillin, TMP/SFX, ceftriaxone, or cefotaxime. Microbiologic relapse occurred in each patient: within 2—4 weeks. Each of the salmon 11a strains was susceptible to norfloxa- cin. Patients were treated with norfloxacin 400 mg bid orally for 30 days. Stool cultures were negative at one week in all three patients. No adverse reactions to norfloxacin were noted during the treatment period. Patients 01 and 52 remained culture negative during a 4-6 week followup period and had no clinical recurrences until their deaths from other AIDS—related infections or neoplasm. Patient #3 had a clinical and microbiologic relapse of salmnella 1 week after norfloxacin was stopped but responded clinically to retreatment with norfloxacin. Norfloxacin appears effective in the treatment of salmonel- la infections in AIDS patients and may be more useful than standard agents in eradicating the organism and preventing clinical and microbiologic relapse. Oral administration and twice daily dosing are significant advantages. Fur- ther studies will clarify its role in the magemmt of salmnel losis in AIDS patients. 188 THR150 Disseminated Histoplasmosis in Patients with AIDS or at high risk for AIDS. WILLIAM C. CARRON, R.S. FISHBACH, R.D MEYER, Cedars-Sinai Medi- cal Center, UCLA School of Medicine, Los Angeles, CA., U.S.A. Four patients with AIDS and l at high risk for AIDS living in Los Angeles, CA. developed disseminated histoplamosis. None of the 5 patients had recently been in a highly endemic area for H. ca sulatum and only 2 patients had ever been in such an area in. the distant past. Histoplasmosis was the initial AIDS defining condition in 4 patients. All patients had constitutional symptoms of weight loss, fatigue, night sweats and unusually high fevers. Chest radiographs and liver functions tests were abnormal in all patients. Cultures of bone marrow in 2 of the 3 patients tested, blood cultures in 2 patients, and biopsies of brain, adrenal gland, and lymph node yielded H. ca sulatum in separate patients. Four patients died; only 1 patient lived more than six months despite antifungal therapy with amphotericin B. A review of the literature showed 54 patients with AIDS and histoplasmosis from all areas. Disseminated histoplasmosis was the initial AIDS defining condition in 31 of 43 patients in whom such data were given. Commonly involved sites were blood, bone marrow, liver, spleen, lymph nodes and lungs. Serological tests were of little value. Improvement during therapy with amphoter- icin B occured but outcome was very poor; relapses during ketocon- azole therapy were common. Disseminated histoplasmosis is an important cause of morbid- ity and mortality in patients with AIDS or at risk for AIDS, including those in non—endemic areas. THP151 Multiple-Dose Pharmacokinetics of Eflornithine in AIDS Patients Treated for W M Pneumonia. THOMAS M_. GILMAN, Y.J. PAULSON, LL. COHEN, P.N.R. HESELTINE, C.'l‘. BOYLEN. University of Southern California, Los Angeles, CA, U.S.A. Eflornithine (alpha-difluoromethylornithine, DFMO) is an irreversible inhibitor of ornithine decarboxylase. We have previously reported eflornithine’s efficacy in treating refractory Pneumocystis carinii pneumonia and the occurrence of severe thrombocytopenia in patients with impaired renal function. Others have reported that the elimination of eflornithine is highly dependent on renal function and so information about multiple-dose eflornithine pharmacokinetics in patients with AIDS is needed to modify dosage and avoid toxicity. The biodisposition of eflornithine was studied in detail in four AIDS patients receiving compassionate therapy for refractory Pneumocystis carinii pneumonia. Intravenous treatment with 100mg/kg IVPB every 6 h was given for 3 to 5 days. Serum for eflornithine assay was then obtained before and 0.5, 1.5, 3, 6, and 12 hours after a dose, while the subsequent dose was withheld. A high—pressure liquid chromatographic assay was used to measure eflornithine concentrations. Pharmacokinetic parameters were determined using a one- compartment model. Creatinine clearance ranged from 75.7 to 101.2 ml/min. At steady—state, peaks ranged from 196.6 to 317.9 mg/L and troughs ranged from 71.3 to 113.3 mg/L. Pharmacokinetic parameters (mean 1 SD) were: distribution volume (Vd) 32.8 : 4.4L, half-life (ti/2) 4.1 i 0.5 hours, elimination—rate constant (Kel) 0.17 i 0.02, and total body clearance (CLtb) 92.3 1 9.9 ml/min. A one- compartment model is appropriate to evaluate the relationship between eflornithine pharmacokinetics and renal function in AIDS patients. THP152 Histologic Patterns of Lymphadenopathies in AIDS: Correlations with ' Progress of Disease. HARRY L. IOACHIM, MANIMALA ROY, WILLIAM CRONIN. Department of Pathology. Lenox Hill Hospital, New York, N.Y. Persistent generalized lymphadenopathy (PGL) is one of the manifestations of infection with immune deficiency virus (HIV) which often precedes the severe opportunistic infections and neoplasias of acquired inmume deficiency syndrome (AIDS). We examined microscopically biopsied lymph nodes of 60 patients, identified characteristic histologic lesions and correlated them with the 13156551109- Of HIV antibodies, TA/Tg lymphocytes ratios and the progress of disease. There were 55 men and 5 women, with a mean age of 37 years. A follow up of 3 months to 8 years showed that 37 patients progressed to AIDS including 23 who died while 23 remained in the stage of PGL. The lymph nodes were classified in 3 types according to predominant histologic patterns: A. hyperplasia of lymphoid follicles with germinal centers showing cytolysis and phagocytosis. B. effaced follicles, diffuse lymphoid and vascular hyper- plasia. C. atrophic fibrosed follicles, lymphoid depletion and hypervascularity. The predominant lymph node pattern in 1981-83 was type A while in 1984-86 type C was more frequent. More patients with types A and 13 remained stationary PGL whereas more type C patients died of AIDS. Patients with type B and C lesions more often developed Pneumocystis pneumonia, CMV infections and lymphoma. Nine patients had repeated biopsies which in 3 cases showed persis— tance of types A and B for up to 2 years and in 6 cases progression from types A and B to C. Lymph node lesions type C consistently correlated with short survival, types A and B with better prognosis. THURSDAY, JUNE 4 THR153 Scales for the Neurological Examination and History in the AIDS Dementia Complex DONNA ORNITZ, HANNAH AMITAI, JOHN J. SIDTIS, RICHARD 14. PRICE, Memorial S oan-Kettering Cancer Center, New York, NY. The AIDS dementia complex (ADC) is a frequent complication of HIV infection which usually develops after the systemic manifestations of HIV infection, but at times will precede AIDS and apparently pursue an independent course. In order to more clearly define the epidemiology, natural history and response to therapy of the ADC, we have attempted to develop standardized neurological history and examination scales to complement formal neuropsycho— logical testing. These involve ADC-directed questions related to cognitive, motor and behavioral dysfunction that are oriented toward functional status. The neurological examination is also scaled to evaluate these same functions by mental status, motor and coordination tests. A long form of this examina- tion has been developed for detailed assessment of neurological natural history and the response to antiviral therapy, while a short form has been developed for larger—population epidemiological studies and for screening examinations. We have begun to use these scales together with standardized functional status scales and neuropsychological tests in HIV-infected indi- viduals ranging from clinically asymptomatic to severe ADC. Preliminary analyses suggest that these neurological history and examination scales cor- relate with traditional functional status scales (e.g., Karnofsky, Kurtzke and Blessed) as well as with formal neuropsychological evaluation (correla- tions ranging from r = .4 to r = .75). These instruments, which will be described in detail, have the advantage of being brief, ADC-specific scales. THP154 Prognosis and Natural History of Pneumocystis Carinii Pneumonia: Indicators for Early and Late Survival‘ CONSTANCE A. RAINIER, DM. FEIGAL, G. LEOUNG, M. CLEMENT, C. HOFSY, University of California, San Francisco General Hospital, San Francisco, CA. Prognostic indicators of 710 consecutive patients (pts) with first episode of Pneumocystis carinii pneumonia (PCP) at San Francisco General Hospital (SPGH) from March through August 1985 was reviewed, a time before AZ'I' therapy became available. All pts were in a high AIDS risk group, had no evidence of non- AIDS immunosuppression, and were men with a mean age of 36 years (range 22- 59). 231 of the group already had an AIDS diagnosis, usually Kaposi's sarcoma, at presentation with PCP. Kaplan-Meier survival analysis showed that 271 (+51) died within the first four weeks after first PCP episode. Pts with initial room air arterial blood gas P02 ( 60 torr had 4 week mortality of 501 versus 141 with P02 > 60 (p-.03). Type of initial drug therapy (trimethoprim / sulfa-methoxazole 681, Dapsone 201, Pentamidine 91, other 31) was not predictive of early or late mortality. Median survival after first episode was 9.8 months. Probability of a second episode of PCP was estimated at 181 at 6 months, 1361 at 9 months, and 651 at 18 months. The second episode mortality at four weeks was 371 (+101): overall median survival was ma months. To create a group comparable to populations eligible for clinical trials after PCP, survival and progression was recalculated for pts living at least 10 weeks after initial episode. 6 month mortality was 181 (+61) and 6 month recurrence was 181 (+61). Hhen planning sample sizes for trials of post PCP pts, the correct clinical subset must be used to estimate expected survival. THP155 AIDS Dementla Complex assoclated y‘lth Braln Rspfllve Antlbodles ' MAHENDRA KUMAR ,L.RESN1CK ,J.BERGER and C.ElSDORFER Departments of Psychiatry' and Neurology"', University of Miami, School of Medicine, Miami, FL and Mount Sinai Medical Center", Miami Beach, FL. The cause(s) of AIDS dementia complex are unknown. It has been suggested that dementia may be a result of direct neurologic infection by HIV,or an indirect effect, such as autoimmune phenomenon. Although HIV has been detected in the CNS, the target cell/s appear to be macrophages and/or glial cells but not neuronal tissue. Brain reactive antibodies (BRAS) are present in patients with dcmcnting diseases such as Alzheimer’s disease and Crucizl‘cldt Jakob disease. We present evidence that BRAs are associated with AIDS dementia. Electroblots prepared from normal human hippocampal tissue were used to analyze BRA activity. Thirty scra samples from HIV scropositivc patients,” with and 12 without AIDS dementia complex were screened for BRAs. The results reveal that 78% of patients (14/18) with dementia, and 33% of patients (4/12) without dementia were positive for ERAS (X’-4.22, p<.04).Thc brain reactive protein in hippocampal tissue has an apparent MW! of 45 kDa. We had observed earlier rho: although 16-30% of normal subjects also have BRAs,the activity is rarely directed against the 45kDa protein.The presence of antibodies in patients without AIDS dementia complex suggests that BRAs may be an early marker of dementiaflowcvcr. prospective studies nccd to be performed to evaluate the role of BRAs in AIDS dementia complex. 189 THR156 Outcome of Subsequent Pregnancies in an HIV Seropositive Woman. ANDREW A. WIZNIA, H.B. WEISS, T.A. CALVELLI, E.H. STEINHAUER, A.RUBINSTEIN: Department of Pediatrics, Albert Einstein College of Medicine, Bronx, New York. We have previously documented that human immunodeficiency virus (HIV) infected women with one infected child have a 66% of trans— mitting the virus in subsequent pregnancies. It has also been postulated that the physiologic immunodeficiency of pregnancy may exacerbate the disease process. We report a 32 year old intra- venous drug abusing woman seropositive for HIV who has a 5 year old son with AIDS. This woman has been clinically well though she was immunodeficient as documented by reversed T4/T8 ratios and abnormal in vitro lymphocyte mitogenic transformations. Two subsequent pregnancies have produced two HIV uninfected children. Her immune aberrations have disappeared and her immune studies remain normal even though she is 20 weeks pregnant. This patient may represent a self reversal of clinical and immunological path- ology. THP-157 Immunotoxicological Properties of lsobutyl Nitrite PATTISAPU R.J. GANGADHARAM‘, V.K. PERUMAL, B.T. JAIRAM, K. PARIKH, National Jewish Center for Immunology and Respiratory Medicine, Denver, Colorado Acquired Immunodeficiency Syndrome (AIDS) is frequent among homosexual men who use licit and illicit drugs recreationally. We have investigated the immunotoxicologieal properties of one such illicit drug, isobutyl nitrite (IBN), in street gargon "RUSH" in beige and C5781/6 mice. Beige mice in general tolerated a less period of exposure to [EN as compared to the C57Bl/6 mice. Beige mice were infected intravenously Mycobscterium avium complex (MAC) and exposed daily, alternate day and twice weekly. The groups having daily inhalation showed high and early mortality (90%) and high CFU counts in the spleen and lungs with progressive decrease in alternate day and twice weekly groups. Oral and rectal routes of challenge with MAC showed similar trends. Mortality with and without IBNgexposure were 90 and 4D, 3D and 0 and 30 and 0, between ISBN treated and controls respectively, with IV, oral and rectal challenges. Statistically significant differences in CFU counts of MAC were seen between IBN treated and control animals in all series. Exposure to 0 to 196 of IBN showed a dose related toxicity on viability of macrophages and lymphocytes from beige and C5781/6 mice. At the optimal concentration, It caused diminished phagocytic indices and greater intracellular growth of the organisms in peritoneal and alveolar macrophages. Exposure of beige and C57Bl/6 mice for 2 to 4 weeks caused increased release of superoxide anion (0;) and hydrogen peroxide (H20 ), decreased NK cell activity but no change in the TH:TS cell ratios. Toxicity o N may operate either through diminution of NK cell activity or through increased release of H202, which in turn, can form toxic complexes with methemoglobin which is a consequence of ISBN administration. (Supported by Research Grant NO. I’ll-21897 from NIH). THP158 Prospective Neurodevelopmental outcome of Infants of ' Seropositive Mothers and Their Controls. JOAN HITTELMAN’, A. WILLOUGl-IBY*', H. MENDEZ‘, J. SILCOTT‘, P. SHAH', S. HOLMAN’ ET AL. *SUNY Health Science Center at Brooklyn, Brooklyn, N.Y., U.S.A. and ”National Institutes of Health, Bethesda, Maryland, U.S.A. As part of a prospective neurodevelopmental follow-up, the development of 18 HIV persistently seropositive infants is compared to that of 28 seronegative controls. The sample is drawn from 2 patient populations: infants whose mothers attend a special substance abuse pregnancy clinic (13 pcs: 18 neg) or a Haitian pregnancy clinic (5 pos; 10 neg). Thirty-five infants have been assessed at 1 month of age using the Einstein Scale: 23 at 3 months and 13 at 6 months using the Bayley Scales, HIV by an examiner blind to the infants' status. Correcting for gestational age, 6 seropositive infants and no controls were found to be developmentally delayed (p<.05). No differences were found between the groups at 1 month of age. At 3 months, mental development scores were lower in the positive group (x-lol) than the controls (it-109; p<.05). The 6 month sample is comprised of infants of substance abusing women only. The seropositive infants had poorer language development (p<.025) and a trend for poorer cognitive development (p<.075) than the controls. Two additional infants, born to seropositive mothers. seroreverted before 6 months of age. Their data is not included in the above analysis; their development is within normal limits. Infants exposed to HIV appear to show specific delays and/or lowered developmental quotients by 3 months of age. THURSDAY, JUNE 4 THP159 Does Concomitant HIV Infection and Measles Infection in African Children Lead to Increased Morbidity and Mortality? MICHAEL G. SENSION*, N. NZILA**, M. DUMA P.**, R. RYDER”, T.C. QUINN***, mm, *Johns Hopkins Univ. Sch. Med., Baltimore, MD, MProject SIDA, Kinshasa, Zaire, ***NIAID, NIH, Bethesda, MD, ****CDC, Atlanta, GA. To determine if concomitant measles and HIV infection augment childhood morbidity and mortality, we are studying 300 children less than 6 years old admitted with clinical measles to Mama Yemo Hospital in Kinshasa, Zaire between Jan-April, l987. Measles cases are confirmed by IgM serology while HIV infection is established by detection of HIV antibodies by repeat ELISA with Western blot confirmation. From Jan. 8-29, 62 children have been enrolled (30 males, mean age = l5.5 months; 28 females, mean age = l8.6 months) of whom 5 are HIV seropositive (896). Of the 5 HIV seropositive children, 2 (#096) have died, and 3 (60%) have improved during hospitalization. Among the 57 HIV seronegative measles cases, 7 (12%) have died and 50 have improved. History of measles vaccination was low among both groups with l HIV positive (20%) and 8 HIV negative (10%) children having previously received measles vaccine. HIV seropositive children were more likely than HIV seronegative children to present with polyadenopathy (60% vs. 142%), a history of diarrhea (60% vs. 30%), or 2 or more of the following symptoms: pneumonia, diarrhea, laryngitis (80% in HIV seropositives vs. 37% in HIV seronegatives). HIV seropositive children were also more likely to have had previous hospitalizations than HIV seronegative patients (40% vs. 12%). The 2 HIV seropositive children who died had a mean WBC of 3,800/mm3 and a mean total lymphocyte count of 97O/mm3 which contrasted with counts of 10,600 and 3,800 respectively, in the 3 HIV seropositive children discharged with clinical improvement. Our final results in 300 children will demonstrate whether measles and HIV infection synergistically increase morbidity and mortality in African children. THR150 Detection of HIV Core Proteins in Biopsied Lymph Nodes from Patients with AIDS-Related Complex (ARC) and AIDS. NORA C.J. SUN, P. SHAPSHAK, K. SUGITA, D. IMAGAVA and G. BEALL, Harbor-UCLA Medical Center, Torrance, CA 90509 Detection and localization of HIV (HTLV-III/LAV/ARV) antigen In the biopsied lymph nodes from patients with ARC and AIDS were studied by an avIdIn-biotin- complex (ABC) method using monoclonal antibodies (MoAb) against HIV core pro- teins p24, p17 and envelope protein gp 120. It was found that all MoAb were reactive with frozen lymph nodes of some patients, but the morphology of posi- tive cells was poor. PZH and p17 were also detectable on formalin-fixed, para- ffin embedded sections, and a stronger reaction was observed when we used MoAb pzh. Eighteen biopsied lymph nodes from ARC patients and 2 from AIDS patients (both had Kaposi's sarcoma (KS) In the nodes) were the subjects for study of p2“ on formalin-fixed, paraffin embedded sections. of I3 lymph nodes which displayed follicular hyperplasia, 8 of them showed strong reaction, 3 of them weak reaction (or occasional cells being positive), and 2 of them were non- reactive. Five lymph nodes which displayed follicular regression and paracor- ticai hyperplasia showed that four of them were reactive with p2“ MoAb and one was negative. Lymph node biopsies from 2 patients with KS showed occasional cells being positive. Most positive cells were present In the follicular (ger- minal) centers, however, the interdigitating reticulum cells, histiocytes and endothelial cells were also positive in some instances. T-cell subsets (Th and T8 cells) study was done in the same specimen (but from frozen lymph nodes) from seven patients. It was found that there was no correlation between the absolute counts of TM and T8 cells in biopsied lymph nodes and the presence or absence of HIV core protein p24. THP161 C tome alovirus encephalitis in AIDS : an anatomo- ' clinlca study of 4 cases. — C. MARCHE*, ADRIEN G. SAIMOT*, S. BARTCZAK", S. MATHERON", R. VAZEUX”, C. VEDRENNE‘”. Hop.Cl.Bernard*,Institut Pasteur’”, Hop. St Anne***, Paris, France. Post-mortem examination of 90 brains from AIDS patients provided evidence of CMV infection in 4(4.4%). Neurological symptoms and signs appeared 2 to 4 months before death. Early symptoms included behavioral changes, confusion,pyramidal tract signs and ataxia. At late stage,dementia,seizures, then coma developed. A mild CSF pleocytosis with protein) 100 mg/dl was noted in 2 pts.In 3 cases CT showed cortical and subcortical atrophia. In one case CT was normal but MRI showed ventriculi- tis. At autopsy, gross pathologic findinds were a ventricular dilatation with peri-ventricular hemorrhage and a rough pattern of ventricular wall. Major histologic features were : small and large areas of polymorphic or histiolymphocytic cells with necrosis and microqlial nodules. Inclusions typical of CMV were present in numerous cells within or without the inflam- matory or necrosis foci. The major lesions were periventricular and/or disseminated in the white and gray matter. Cerebellum was also involved. In all cases immunoperoxidase staining proved conclusive for CMV, negative for I-lsv-l and 2. HIV-RNA and proteins were not detected in 2 brains tested for. EM confirmed the diagnosis in all cases. CMV encephalitis was probably the results of overwhelming disseminated CMV infection in 2 pts, but not in the 2 others. These data suggest that subacute CMV encephalitis is not as rare as reported in AIDS. 190 THB162 A COMPUTERISED NEUROPSYCHOLOGICAL BATTERY FOR THE ASSESSED”? 0!‘ HIV INFECTED ADULTS WITH BMTHASIS 0N DETECTION OF EARLY CENTRAL NERVOUS SYSTEM INVOLVEMENT Agnes Lodynski, Clemency A. Palmer and John Green. Psychology Department, St. Mary's HospitalI London ENGLAND. This paper presents a new and comprehensive psychomsntrlc aaaasamsnt battery for the detection and categorisation of tha ao—callsd AIDS Damantla Complex. The battery Includes two sets of sonsltiva computerized tests which even lll subjects find rewarding and Interesting. The performance of standardised controls, asymptomatic HIV—positive, PGL, ARC, and AIDS groups were compared in two studies, the second of which is the first stage of a two year longitudinal project. Early results indicated impairment in those tasks which demand more complex information processing and It is argued that early central nervous system involvement - the achievement of which ls aapaclally vital clinically - In most sensitively detected by using paradigms derived from experimental work on Attention and Performance. The effectiveness of this approach I: illustrated using results from a computer administered dual-attention task. THP163 Identification of Pneumocystis garinii (PC) in sputum; ' underestimation of cyst number with Giemsa. WALTER BLUMENFELD, W.I(. HADLEY, J.M. GRIFFISS, University of California San Francisco, San Francisco, CA. The diagnosis of PC pneumonia is currently based on morphologic recognition. The Giemsa stain demonstrates both the trophozoite and cyst forms. Its use has led to the impression that the trophozoite predominates in AIDS. This study was undertaken to determine which of several stains results in easiest recog- nition of PC, and to compare cyst number as seen by different stains. l6 dithiothreitol—liquefied PC-positive, frozen induced sputums were simultam - ously thawed. Each sputum was vortexed and equally distributed onto 5 slides. The following 5 stains were done: (1) Giemsa; (2) toluidine blue; (3) silver methenamine; (4) toluidine blue/Giemsa; and (5) silver methenamine/Giemsa. Each slide was evaluated for number of recognizable units of PC at 10x, and number of cysts at 100x power. With stains (1),(4), and (5), the size of each PC aggregate was measured with an ocular micrometer. There was no difference among the stains in detectable number of units of PC organisms or amount of PC aggregate area. Howsvet, median number of cysts/squint of PC aggregate area on Giemsa was 6.1 x 10 (range — 11.5 x 10 , interquartile interval 3.6-6.9 x 103), compared with 16.9 x 10 with toluidige blue/Giemsa grange 0 - 62.8 x 103, interquartile interval 7.7 — 45.4 x 10 ) and 6.7 x 10 with silver methenamine/Giemsa (range 0 - 57.6x103, interquartile interval 0.4 - 12.7 x 103). Cyst recognition with silver methenamine was hindered by the large amount of nonspecific silver staining. All the evaluated stains are equally suitable for diagnostic screening purposes. When accurate enumeration of cysts is important, the Giemsa stain, in comparison to toluidine blue, under- estimates the number of cysts. 1113164 Evaluation of Infectlous and Immunologic Status by Bronchoalveolar Lavage In Patients with AIDS and ARC. T. MAY°. CH. KOHLER '. N. DELORME °°. H. GERARD'. G. FAURE ", P. CANTON° Servlces des Maladies Infectiouses° et des lnsulflsants resplralolres“ - Laboralolres d'hislologIe-Embryologie‘ at d'lmmunologle“. CHRU Nancy Brabols FRANCE. Bronchoalveolar (BAL) was carrled out In 17 AIDS and In 10 ARC wlth the alm of establishing an etiologic diagnosls of lung opponunlst Infection and to analyse the profile of immunocompetent alveolar cells. In patients presenting with cllnlcally and/or vadlologlcally proven pneumonia. BAL revealed at least one opportunist pathogen In every case whereas II was negative In patients presenting neither clinical nor radiologlcsl slgns of pneumonla. The analysis of the cells obtained by BAL showed that ARC group of pallenls presented hypercellularlly (meantSEM) : 295x103 c i108x103 (ARC); 164x103 c :29x1oa (AIDS) (s 200x103 C In controls). Alveolar lymphocytosls was Increased (AIDS : 26 i 5.7%; ARC : 25.2 :I: 7.4 %; s 15 % In control) contrastlng markedly wlth lymphopenla In the peripheral blood (AIDS : 33 17.2 cells(CD4) at 150 1 40.8 cells(CDS); ARC : 271.7 1 64.8 cells(CD4) at 436.7 1 85.9 cells(cDB). Most of the alveolar lymphocytes expressed COB phenotypes whereas CD4 were severely depleted (CDA/CDSratlo : 0.16 (AIDS); 0.20 (ARC). BAL appears to be an excellent mean for the dlagnosls of lung Infection but It also provides a new approach for studylng the local Immunity In the Immunocompromlsed pallents. We have undertaken a prospective study In asymptomatic HIV posltlve patient. The prellmlnary results In thls thlrd group suggest also modlllcatlons of the local Immunity of the lung. THURSDAY, JUNE 4 THP165 Echocardiography detects cardiac involvement in Acquired Immunodefi— ciency Syndrome(AIDS): study in 70 patients. SALVATORE CORALLO,M.R.MUTINELLI,M.MORONI*,A.LAZZARIN*',G.BAROLDI“*,Cardiac,In- fectious Dis.*and C.N.R. Pathology*Dpts,University of Milan,"L.Sacco” Hospital Milan,Italy. Little is known about cardiac involvement in AIDS.On that purpose 70 consecu- tive patients(pts)(mean age 29:7 sd years) 54(77%) males and 16(23%) females with AIDS diagnosed clinically and serologically were examined by means of TM and 2D Echocardiogrsphy with the aim of detecting cardiac abnormalities(C.A.). 64 Pts were affected by opportunistic infections,6 by Kaposi's sarcoma. No pt showed clear signs of heart failure. Results: 49/70(70%) pts showed C.A. characterized by left ventricle(LV) walls thickness(mean 8.3102 mm),systolic thickening (mean 3913 %) and particularly LV % shortening fraction(27:5) impor— tant reduction. 28/70(40%) Pts showed pericardial effusion.moderate in 23,cos— picuous in 5. Moreover in 20 pts LV antero-apical dyssynergy and in 1 pt LV in— tracavitary mass was found. In 25 pts in clinically advanced state LV was globg lar and poorly contracting. 18 Pts died and necropsy showed in 12 pts globular shape of the heart,four chamber dilation,and LV walls thinning. Conclusion:de_s_ pite little clinical suspicion C.A. in AIDS are frequent. An impairment in LV contractility appears to be the first Echo finding;followed by LV walls thin- ning,pericardial effusion and eventually by LV cavity dilation. This evolution is suggestive of myocardial damage induced by Human Immunodeficiency Virus. Echocardiography proved very helpful in detection. THE166 Neopterin Levels Correlate with Walter Reed Staging Classification of HIV infection. DIETMAR FUCHS“,H.WACHTER*,H.JAEGER**,M.POPESCU**,et al.,*Insti- tute for Medical Chemistry and Biochemistry,University of Innsbruck,Austria,**AIDS Study Group, Schwabinger Krankenhaus Munich,FRG. In vitro and in vivo data contribute to the evidence that neopterin represents a sensitive marker for activation of macrophages by interferon—gamma. Due to the origin of interfe— ron—gamma elevated neopterin is also characteristic for activation of T—cells. Since in vitro the production of HIV strictly depends on activation of T-cells there is a basis that neopterin might reflect the clinical state of HIV infection. To investigate the importance of neopterin in HIV infection 50 male subjects in different stages of the Walter Reed staging classification were repeatedly tested for neopterin levels in urine and serum over a three months period. Neopterin was measured in urine samples using HPLC standard techniques and in serum by using RIA. Urinary neopterin levels were related to creatinine. In addition, data from the medical history, physical examinations, whole blood cell count, blood chemistry, HIV serology, in vitro and in vivo tests for cellular immunity were collected. Neopterin levels in urine and in serum showed a significant correlation with the Walter Reed staging classification. Neopterin levels in urine and serum rose with progression of the disease as measured by the W8 classification. THP167 Flexible Fiberoptic Bronchoscopy and Bronchoalveolar Lavage (B.A.L.) for Diagnosis of Opportuniltic Infections in Pediatric Patients with A.I.D.S. J.A. BIRRIEL JR , S. GOLDFINGER , G. SCOTT , M. MASTRUCCI - , D. VERNON , B. HOLZMAN , et.al., University of Miami, School of Medicine, Miami, Fl. We report our experience with the technique of B.A.L. using flexible fiber— optic bronchoscopy in 10 children with A.I.D.S. Indication for the procedure was worsening in pulmonary status in patients previously diagnosed as having A.I.D.S., or evidence of interstitial pneumonia in patients with a presumptive diagnosis of opportunistic infection. From a total of 10 patients, four la— vages were positive for Pneumocystis carinii; one was positive for Pneumocystis caring and Pseudomcnss Aeruginosa (cultures from B.A.L. and blood were also positive for Pseudomonas)., and five lavages were negative. Pathological exami- nation by way of autopsy in three patients correlated 1001 with bronchoscopy findings. (positive for Pneumocystis carini , positive for Pneumocystis carinii and Pseudomonas,and negative for opportunistic infection.) The most common complication was mild to moderate epistaxis in 3 patients; one patient required endotracheal intubation due to C02 retention. In the majority of cases, the pulmonary involvement in pediatric patients with A.I.D.S. is due to opportunistic infections or lymphocytic interstitial pneumonia. The flexible fiberoptic bronchoscopy with bronchoalveolar lavage offers an effective and relatively safe method for the diagnosis of opportu— nistic infections in this population of patients. 191 HIV-Infection in a C hurt of H mophiliacs THB168 HUMAS G.A. AMRADTq, D.NIESE3, H.H.BRACKMANN2, A.5TEINBECH ,M.MARTINI , 1: Medizinische Universitfltsklinik,8onn, FRG,2:Inst1tut ffir sxperimsntelle Hamstologie, Bonn,FRE 760 hemophiliacs are treated at the Institute for experimental hematology, University of Bonn. Of these, #75 (61%) are infected with the Human Immunodeficiency Virus (fill). The percentage of fill—infection differs depending on the number of factor units the patients received. 16h Ell-infected hemophiliacs were seen as outpatients at the Medical Clinic,University of Bonn. 7B (h7,5%)uere symptomless carriers of the virus, 86 (52,5%) displayed symptoms of the fill- infection, 27 of them having less than 100 EDA lymphocytes/ul blood. From 1982 through January 1967 15 hemophiliscs developped AIDS according to the CDC-criteria. 10 of them had their primary mani— festation in 1956 or 1987. These were opportunistic infections in 10 patients, neurological manifestations in 5 patients, and malig- nancies in 2 patients (2 patients had more than one initial mani- feststion). The 5 fill—infected female sexual partners of hemophiliacs 1n- vestigsted so far are symptomlsss carriers at present. Our data do not show any different natural history of HIV-infection on in hemophiliacs as compared to other risk groups. THE169 Acute hepatitis during human immunodeficiency virus (HIV) primary infection. PIERRE-MARIE GIRARD, S. MATHERON, M.A. REY, C. MICHON, J.P. COULAUD, A.G. SAIMOT et a1., Hopital Claude Bernard, 75019 Paris, France. Acute hepatitis was observed in 7 adult patients (pts) (6 males, 1 female, aged from 23 to 41 years) among 15 well documented cases of HIV primary infection. All pts had fever with other symptoms and signs (sore throat : 6, rash : 7, meningitis : 3, adenopathies : 10, splenomegaly : 4, dysphagia : 3, diarrhea : 6). HIV primary infection was assessed by sequential serum ELISA and Western Blot. In the 7 pts with hepatitis, HIV was transmitted through sexual intercourse (5 pts) and direct parenteral exposure (2 pts). Transaminases raise was observed from 8 to 53 days after the onset of fever (mean ASAT peak : 8.8 x normal value). Mild cholestasis (Alkaline phosphatase : 2 x normal value) occurred in one pt. One pt was subicteric and non specific digestive symptoms were observed in five. Needle liver biopsy showed mild cytolysis with portal inflammation in 2. Liver function tests returned to normal within 10 weeks. In all pts other hepatitis agents were ruled out by negative virus isolation (CMV), negative antigenemia (HBV) and lack of IgM antibodies and/or seroconversion (HAV, CMV, EBV, HSV, Treponema, Toxoplasma) on repeated tests. Acute hepatitis seems common during HIV primary infection (46%). Although concomitant non A-non B virus infection cannot be definitively excluded, hepatitis might be due to HIV itself- THE170 Anti—D and anti—c immunoglobulin for HIV related thrombocytopenic purpura. Eric OKSENHENDLER", Y. BROSSARD", P. BIERLING"*, P.M. GIRARD"*", C. SCHENMETZLER' and J.P. CLAUVEL‘. ': Hopital Saint-Louis, ”: Centre d'Hémobio- logie Périnatale, "‘z H6pital Henri Mondor, ""z Hopital Claude Bernard, PARIS, FRANCE. The potential risks of steroids and splenectomy in HIV infected patients led us to evaluate the efficiency and safety of anti-D and anti—c immunoglo- bulin in 9 adults with HIV related thrombocytopenic purpura. They were 5 drug addicts and 4 homosexual men ; all had HIV antibodies but none had full blown AIDS. None were splenectomized. The platelet count was below 15 x 10 /l in all patients. The 7 Rh+ patients received 1,000 g (12 to 20 rig/Kg) of anti—D IgG (Bio—Transfusion, France) intravenously on 2 consecutive days. The 2 Rh- patients were given an equivalent dose of anti-c IgG ( ml of plasma from a single donor). A significant platelet rise above 50.10 /1 was obtained in 6 patients. Repeated boosters were efficient in 4 cases. Direct antiglobulin test became positive in all patients and serial quanti— tative evaluations of IgG coating of red blood cells (RBC) were performed in 4. Only one patient experienced a significant hemoglobin drop. Eluates of platelet bound IgG were not modified by the therapy. To further elucidate the mechanism of the therapy. two patients received consecutively both regimens : one Rh+ (0+, D+, 131-, c-, e+) patient who responded to anti—D IgG received one course of the anti—c regimen without any significant response. One Rh— (C—, D-, E—, c+, e+) patient did not respond to anti—D but had a good response with anti-c IgG. These data suggest that anti-Rh IgG can be efficient and safe in patients with HIV related thrombocytopenic purpurs and that a specific interaction between RBC and anti-Rh antibodies is required. THURSDAY, JUNE 4 THE171 Mediastinoscopy and Mediastinal Lymphadenopathy in AIDS Patients. JIHAD SLIM, G.E. TONNESSEN, G. PEREZ, E. PEREZ E.S. JOHNSON. St. Michael's Medical Center, Newark, New Jersey. A 16 month experience (8/85-12/86) involving mediastinoscopies in AIDS patients led to the following review. In this period 10 procedures were done and all yielded diagnoses. Only one patient suffered any sequelae. All 10 patients had posi- tive gallium scans prior to the procedure, 80% chest x-ray evidence and 90% CT scan evidence of adenopathy. All the patients had bone marrow biopsies with no diagnoses and one non-diagnostic peripheral node biopsy. All the results were infectious in origin with 20% showing cryp~ tococcus (both with + serum crypt antigen) and 80% showing acid- fast bacilli. In the acid—fast group 3 of 8 were mycobacteria scrofulacium, 1 of 8 mycobacteria tuberculosis and 2 of 8 did not grow. Except for one post operative mortality all clinically improved on therapy initially, but 6 of 9 eventually died with all still showing evidence of their original disease at the time of death. These results suggest that mediastinoscopy is a safe valuable diagnostic procedure. Also infections are the primary causes of mediastinal lymphadenopathy with malignancy conspiculously absent. THP_112 ALTERNATIVE SITE COUNSELLING AND HIV SCREENING. §M Burns, RP BRETTLE, C Bisset, J Davidson, 5 Davidson, JMN Gray et a1. City Screening Clinic, Edinburgh, Scotland. Extensive infection with Human Immunodeficiency Virus (HIV) amongst intravenous drug misusers (IDMs) ocurred in Edinburgh between 1983 and 1985. with the introduction of routine HIV screening of blood donations would current and ex IDM attend an alternative counselling and screening clinic outwith the Blood Transfusion Service and Sexually Transmitted Diseases service? In one year from October 1985 - September l986 441 individuals attended the City Screening Clinic (CSC) for counselling. There was a 35% default rate on the first appointment, a 21% post test default rate and a test refusal rate of 7% which ranged from 2.5% in IDMs, 3% in their sexual contacts, 7.5% in homosexuals, 9% in heterosexual contacts to 20% in those with no identified risk activity. Of those attending 43.5% were IDMs, 20% their sexual contacts, 12% heterosexual contacts in general, 9% homosexuals/bi— sexuals, 3% had been exposed to blood and 12.5% with no identified high risk activities. The overall HIV seropositivity rate was 26%, 52% in IBM, 10% in homosexuals/bisexuals and 7% in sexual contacts of IBM. Despite initial sceptism there is a place for an alternative counselling and screening Clinic on a site distinct from the Blood Transfusion and Sexually Transmitted Diseases services directed towards but not just for IBM. THP173 Lessons of History: How best can we buy time awaiting a vaccine ' for HIV? CHARLES F. CLARK, M.D., AUSTIN C. KUHN, MSW, SHAPE Hospital, Casteau, Belgium, RAY MOEHRING, Boulder, CO, EDMUND C. TRAMONT, M.D., Walter Reed Army Institute of Research, Washington DC. Recognizing that HIV is a sexually transnitted disease, we can gain some insights into the probable dynamics of the HIV epidemic by looking at syphilis information from the prrantibiotic era. In 1917, a survey using the Wesserman blood test in United States Army personnel showed a 16.77% positive rate overall, a 16.l8% rate in white enlisted men, and a 36.0% rate in black enlisted men. Oler the next 25 years, major efforts were made to reduce the prevalence of syphilis in the United States. Educational programs were launched to teach the population about human reproduction, the venereal diseases and how to avoid them. Prostitution was suppressed, and the case finding technique with medical treatment of positive contacts using Arsphenamine was developed. The effectiveness of this multipronged attack is seen in the Wasserman Blood Survey data of 2 million world War II recruits in 1941. The overall rate was 4.77%, with a white rate of 2.35% and a black rate of 27.2%. Fran this data we would drawn several conclusions: (a) That multiple efforts, including a nodestly effective treatment, will reduce but not stop the spread of a sexually transnitted disease, thereby buying time for the development of a vaccine. (b) Minority groups require specialized programs with exceptional allocation of resources. (c) Massive crash educational programs will alert the general population to the danger of HIV, but a long term thoughtful multifaceted program will be required to significantly slow-the spread of HIV. 192 THP114 HIV Laboratory Reporting: The First 12 Months in Colorado FREDERICK C. WOLF, C. RAEVSKY, N. SPENCER, S. VALWAY, Colorado Department of Health, Denver, CO, U.S.A. In November 1985, the Colorado State Board of Health required laboratories which collect or process specimens in Colorado to report individuals testing positive for HIV antigen or antibody to the Colorado Department of Health (CDH). The regulation was implemented in February 1986 by CDH staff visits to clinical laboratories. The controversial regulation which is similar to those for syphilis and gonorrhea, has been complied with. In 1986, 391 reports were submitted (average 32.6 per month) by 38 laboratories (21 in Colorado and 17 in other states including commercial, federal, military, hospital and plasma laboratories). The number of reports by laboratory averaged 10.3 (range 1 to 75). Compliance is illustrated by completion rates for patient data (name, 94.6%, date of birth 69.8%, sex 92.1%, race 51.9%, address 67.5%), provider data (name 94.1%, address 70.9%), and laboratory data (name 98.0%, test date 79.0%, test type 93.1%, test result 91.6%). Reported positives (391) were predominantly men (323, 82.6%), although 37 (9.5%) were women. Most (61.8%) reports were on persons between 20 and 34 years old. Patient name allows identification of repeat tests on individuals (391 positives on 363 individuals). Although number of tests processed is currently being collected, positive reports from these laboratories accounted for approximately 24% of all newly identified HIV Ab positive tests in Colorado during 1986. HIV laboratory reporting by name is a practical and essential program to understand the full scope of the HIV epidemic and trigger follow—up for prevention counseling. THP175 HIV Seropositivity in Newborns: A novel method for estimating ' prevalence of infection In childbearing women. GEORGE F. GRADY, V.P. Berardi, R. Hoff, M.L. Mitchell. Department of Public Health, Boston, MA As a prerequisite for designing programs to reduce perinatal transmission of HIV, we determined the rate of seropositivity at birth among Massachusetts infants of various demographic characteristics. Individual anonymity was assured by removing identifiers from the PKU (filter paper-adsorbed) blood specimens that were used for microassay of HIV antibody. lmmunoblot was used to confirm an lgG-speclfic immunofluorescence amy that detected antibody primarily of mater— nal origin. Births from Dec'86 through Jan'87 provided 4919 specimens in three batches from groups of hospitals with the respective characteristics of "inner city“, mixed metropolitan, and suburban/rural, and which represent about 45% of state- wide births. Massachusetts Inner Mixed Suburban Not Q1 Metro and rural tested Totals Annual births 5385 18,256 12,266 43,845 79,752 Number tested 849 2,499 1,571 — 4,919 HIV Ab(+) 13 8 2 - 23 (Rate /1000) (15.3) (3.2) (1.3) - - The concentration of seropositivity in Inner city hospital births (15.3/1000) was not unexpected but the widespread distribution of rates between 1/1000 and 3/1000, and the assumption that 1/1000 was the minimal rate among hospitals not sampled, led us to a minimum estimate of 2.6/1000 as the state-wide average. 1112175 A Model for Assessing Statewide Needs for HIV Prevention and Risk Reduction Education KAREN A. HECKERT. K.L. MACDONALD, R.N. DANILA, M.T. OSTERHOLM. Minnesota Department of Health, Minneapolis, MN, U.S.A.' The Assoclation of State and Territorial Health Officers and the Centers for Disease Control have recommended the development of conmunlty education and risk reduction efforts to prevent transmission of Human Immunodeficiency Virus (HIV) in every state. The MN. Dept. of Health is implementing a comprehensive statewide risk reduction and disease prevention plan to identify. assess, and respond to professional, community, and client needs. This plan applies L. Green's health education planning model, PRECEDE, for determining appropriate educational strategies by collecting epidemiologic, social, behavioral, and educational data. Ongoing AIDS surveillance, HIV counseling and testing, and community programs serve to collect some of these data. We have also developed eight survey tools designed to collect information on knowledge, attitudes, risk behaviors, and availability of community resources from health—care providers. public health professionals and persons at high risk. These surveys include: 1,000 persons randomly selected from the general population, 500 gay-identified men, 300 intravenous drug users, 180 persons with hemophilia, 600 randomly selected family practitioners and internists, all 75 infection control practitioners in acute care facilities, 1,000 hospital nurses with potential exposure to HIV and all 73 public health nursing directors at local health departments. Implications for educational strategies for clinical providers, public health professionals and at risk clients are drawn from survey results and may have valuable application to other low prevalence states. THURSDAY, JUNE 4 THR177 Evaluation of an AIDS Education Unit for High School Students. LESLIE MILLER, University of Washington and A. Downer, Seattle- King County Health Department, Seattle, Washington, U.S.A. We conducted a survey to assess the effects of an AIDS curriculum on high school students' knowledge and attitudes about AIDS. The survey contained 23 items and was administered to a population of 240 eleventh graders before and after instruction. When scores were compared for percentage correct responses on knowledge items, scores following instruction were 161 higher. Significant changes were observed on most questions; e.g., students learned that kissing, giving blood and food handling are not major risk for AIDS transmission. Prior to instruction, 711 of students believed that sharing needles was a risky behavior compared to 921 after the class. Attitude questions were grouped and scored on the basis of restrictive and fearful versus tolerant and compassionate beliefs about people with AIDS. A 151 increase in tolerance was observed following instruction, corresponding to the 16% increase in knowledge about AIDS. When asked prior to instruction where they learned about AIDS, only 301 of students mentioned school. Schools become the major source of learning (72%) after only one hour of instruction. In conclusion, apparently even one hour of AIDS instruction can positively impact what young people know about AIDS. More importantly, knowledge appears to influence attitudes. This may enable an adolescent to make informed decisions about AIDS as a public health issue and to make safer choices in risk~taking behavior. THP178 Needle cleaning knowledge among intravenous drug users in treatment and AIDS pcvendutpflky W‘, AS ABDULQUADER“, SR FRIEDMAN‘, DC DFS JARLAIS”, M MARMOR‘”, S BARTELME““, st 21., ‘Narcotic and Drug Research, Inc., ”NY State Division of Substance Abuse Services, “New York University Medical Center, N.Yu NSY Proper sterilization of needles may be important in reducing HIV transmission among IV drug users. In a 1986 survey, 164 patients in a large Neonrk City methadone maintenance program were asked what they thought was the "best way to clean needles.’ While 43 subjects (26%) said only that one should "always use new needles," 121 (73%) named at least one medically-accepted cleaning method. Among the latter, alcohol (64%)~tl'te traditional method among IV users-and boiling (43%) were named most often; few (12%) knew about the recently promoted bleach method, and none knew about peroxide. However, being able to name a method does not always mean that subjects know how to use it correctly. Gender, education, and minority status had no relationship with knowledge of at least one medically-recognized effective method (alcohol, boiling, bleach, peroxide). There were relationships with subjects' drug use patta'ns. The most likely to show needle-cleaning knowledge were the moderately-frequent injectca's: those who, during the year preceding the interview, had continued to inject but on u less-than—daily basis. Similarly, those who last injected more than a month but less than two years before the interview were most likely to know how to stailize needles. These moderately-frequent and moderately-recent injectors participate in both street-drug and warrant worlds and while still ' ‘ 5 maybe, ' l. ‘with disease, 2,... Policy implications imlude: 1) the importance of needle-cleaning education efforts among frequent injectors, who have both the highest infection risk and the least cleaning knowledge; 2) the untapped ‘ ' ' ‘ , ’ ' ofthe ‘ ' ' who might be usedas informal information conduits from treatment programs to street users. THE179 Sexual Behavior Change among HIV Seropositive Individuals. DAVID NVANJOM*,N.GREAVES*, R.DELAPENHA*, S.BARNE$*, F.80YNES*, VLR. FREDERICK*. *Howard University Cancer Center, Washington, DC. Sexual behavior was assessed in 95 HIV seropositive subjects enrolled in a prospective study of the natural history of AIDS to determine if there was sig- nificant sexual behavior change as a result of supportive counselling and edu- cation provided durtng the study. All 95 subjects (65 males, 30 females) were seen by the same investigator during the 12 month evaluation period and receiv- ed the same intense one-on-one counselling and education regarding safe sex practices. The subjects were categorized into group (1) 46 homosexual men, group (11) 36 intravenous drug abusers (IVDA) and group (111) 13 blood trans- fusion recipients and heterosexual contacts. At entry and at each 3-monthly visit subjects were asked whether they had adopted each of 3 modifications.Data collected showed that 85% had fewer different sexual partners, 76% had adopted safe sex practices and 73% began condom use during sexual activity. Since en- rollment 23% had not adopted any consistent modifications in their behavior. Overall sexual activity decreased significantly in all subgroups in terms of number of partners, specific high risk activities and failure to use condoms. The greatest change was seen in group 1 subjects and was more striking in males than females 1n each of the other subgroups. The least change was among IVDA proétitutes. Among 22 patients who failed to adopt any consistent modification, 7 developed STD's and 6 were involved in a pregnancy. These findings suggest that ongoing counselling and education about AIDS leads to changes in sexual behavior among HIV infected persons. 193 THP180 Analysis of Variables Impacting on Safe Sexual Behavior Among Homosexual Men in an Area of Low Incidence for: AIDS Leonard H. Calabrese‘, Buck Harris“, Kirk Easley*, *Cleveland Clinic Foundation, Cleveland, OH, **Ohio Department of Health, Columbus, OH. In an effort to assess the impact of risk reduction education targeted at: the male homosexual community in Northeastern Ohio, 303 men attending one of two homosexual social outings were studied in the fall of 1986 by means of a questionnaire describing their recent sexual practices as well as a number of variables including basic demographics, sources of information of safe sex, personal knowledge of their HIV serologic status, use of available medical resources and others. Among the respondents only 28% (Group—I) were practicing totally safe sex with 71% (Group—II) persisting in some activities that have been clearly described as unsafe. Among Group-II the vast majority admitted to some modification of their sexual behavior: and 75% admitted to feeling comfortable that they have taken adequate sexual precautions. In addition, among those who had not been tested for HIV antibody (n=210) 95% predicted that they would be seronegative. Univariant and multivariant: analysis comparing Group-I to the elicited variables revealed no association between safe sexual behavior and any of the elicited variables including knowledge of a friend with AIDS, personal knowledge of their serologic status, or receiving advice on AIDS from a physician. We conclude that educational efforts on safe sex education in our area have resulted in clinically meaningful behavior modification in only a small segment of the socially and sexually active homosexual community. Furthermore, additional studies are urgently needed to define the barriers to change so that clear and effective educational programs can be developed. THP181 Needs Assessment and Development of Model Standards for AIDS ' Primary Prevention in California E. MICHAEL GORMAN*, D. FRANCIS**, D. KANOUSE*, B. DECKER***, *The RAND Corpora— tion, **California Dept. of Health Services, ***California Health Policy Research Foundation Despite widespread discussion about AIDS prevention, no model standard or masterplan for primary prevention exists. To remedy this situation, the California Health Policy and Research Foundation and the Department of Health Services have developed a set of model standards for prevention that are re— sponsive to needs and resources at the community level. These are based on recommendations of the 1986 Institute of Medicine Report and are informed by relevant prevention literature and expertise of California's public health, research and service provider communities. To establish a baseline of the state's prevention needs, we undertook site visits in five counties representa— tive of a diverse range of geographic and population characteristics. Activities and information assessed included surveillance (case reporting for AIDS and ARC), seroprevalence data on general and specific populations, screen— ing activities, educational interventions, skill building programs, drug abuse programs, special population activities, and program evaluations. In addition, we ascertained size, political and socioeconomic characteristics and location of at—risk populations and their accessibility for primary prevention interven- tions. We identified gaps between the proposed model standards and ongoing pro— grams and made recommendations to narrow the gap. We believe that both the model standards and the process of assessing local prevention needs are generalizeable to other state or regional prevention and planning efforts. TiiB132 A Comparison of Three Educational Models For Changing AIDS Risk- Associated Behaviors JOANNE MANTELL, ANTHONY DIVITTIS, LEE KOCHEMS, PETER MASTROIANNI, KEVIN MAHONY, CHARLES MCKINNEY A community—based risk reduction program was conducted to test the relative effectiveness of three educaupnalstrategies in changing AIDS-related knowledge attitudes, behavioral intentions and behaviors among a sample of 515 gay and bisexual men. Men were randomly assigned to a cognitive-behavioral (CB), cognitiveaffective (CA) or cognitive only (C) condition. The C3 and CA curricula were six- session groups in which a didactic presentation about AIDS, its transmission and modes of protection were given, followed by a group process. The CB group process used skill-building behavioral techniques. The CA process focused on participants' emotional responses to the information. The C group received weekly mailings matched to the content of the other two strategies. All groups completed a baseline screening instrument, a pre-test, and a post- test, at program completion and four.months later. The battery included self- report measures of knowledge and attitudes about‘AIDS, perceived susceptibility self-efficacy, self-esteem, personal control, adequacy of supports, and risk- asaociated intentions and behaviors. Preliminary analysis of the screening instrument indicated that of those participants who engage in anal sex, 361 rarely or never use a condom whether the active or passive partner (n-281; n-231, respectively). Of the partici- pants who engage in either active or passive oral sex, 80% indicated that they rarely or never use a condom. Data regarding the relative effectiveness of each program based on pre-test and post-test 1 data are being analyzed, and will be presented. THURSDAY, JUNE 4 THB183 Statewide Free Condom Distribution Program THERESE MCCLUSKEY, c. WUNDERLICH, A. WILEY, Maryland State Depart— ment of Health and Mental Hygiene, Baltimore, MD. Proper use of condoms are an effective method to prevent AIDS and other STD infections. In an effort to make condoms available, the concept of "Three—For—Free" was developed by the Maryland State Department of Health and Mental Hygiene. The purpose of "Three—For-Free" is to decrease the number of barriers to condom use by making free condoms and instructions available for anonymous pick—up at as many sites as possible in Maryland. At most sites, bags of condoms and instructions are placed on tabletopa in hallways, waiting rooms, bathrooms or clinic examination rooms. As of December 1986, "Three—For-Free" sites have been established in thirteen county health departments, five social service agencies, three Maryland universities, and eight clinics in Baltimore City. In less than one year, approximately 75,000 condoms with instructional pam- phlets have been distributed through this program. The State of Maryland also supplies free condoms to Baltimore City STD clin— ics. In order to increase the availability of condoms to risk groups in Mary— land, the State Health Department supplies condoms at cost to a non—profit community agency for distribution to high risk groups. An illustrated, wallet-sized pamphlet has been developed to be distributed along with the condoms. THP184 Street Outreach AIDS Prevention Program for IV Drug Users. JACK STEIN. B. M. Branson, G. Hurd. Health Education Resource Organization, Baltimore, MD. USA. Estimates indicate only 10% of IV Drug users are in treatment at any one time. In order to accomplish effective AIDS prevention among the 90% not in treatment, a program was designed to assimilate peer AIDS education outreach workers into known drug use communities in Baltimore City. Reformed IVDU's who had successquy undergone treatment were recruhed and trmned about AIDS, with specific emphasis on viral transmisslon, prevention guidelines, and communication skills. The workers were well-received, and pre- and post- intervention evaluations demonstrated a significantly increased awareness among targeted IVDU's not in treatment programs. Success of the program depended on careful selection of outreach workers. Successful candidates were identifed by scores on a rating scale incorporating factors such as drug abusing history. length of time in treatment, treatment progress, reading and educational level, interpersonal skills and motivation level. Team building and organizational support were identified as significant components in outreach workers‘ abilities to cope with job-related stress, including return to drug use. THP185 Motivations and Consequences of AIDS Antibody Testing Amo ' Heterosexuals. SUSAN KEGELES, JOSEPH CATANIA, AND THOMAS University of California, San Francisco, School of Medicine. This study was designed to determine demographic characteristics of hetero- sexuals seeking antibody testing, to assess why heterosexuals seek antibody testing, to obtain data on measures of susceptibility and anxiety specific to AIDS, and to determine consequences of antibody testing. Data on 232 respondents were collected at two antibody testing centers in Alameda County, California; k0.51 (n'124) were heterosexuals. Respondents were administered questionnaires when they arrived at the testing sites, and were followed at 1 and 6 months post-testing. Approximately 651 of heterosexuals had sought antibody testing because of concerns that they may have contracted HIV from sexual contacts; approximately 20% had sought testing because of concerns they were IV drug users, with the remainder being concerned because of trans— fusions (101) for miscellaneous reasons (51). Approximately 261 of the males and 32% of the females were continuing to engage in high risk sexual activities in the month prior to obtaining antibody testing. Perception of increased susceptibility for AIDS were associated with greater anxiety over the possibility of developing AIDS. However, male heterosexuals (even when seeking testing) perceived themselves as less susceptible to contracting HIV than male homosexuals. Antibody postive status was associated with reductions in high risk behavior than antibody negative status. ng J. COATES, 194 1113185 Voluntary Screening For HIV Infection In Patients Attending A Sexually Transmitted Diseases Clinic CARL J. BETTINGER*, H.F. HULL*, N.M. KELLER*, D.J. DUNNUM**, C. SCH/1118*”, and 3.3. MERIZW". *Health and Environment Department, Albuquerque and Santa Fe, NM; **NM AIDS Services, Albuquerque, NM; ***UNM School of Medicine. Albuquerque, NM To determine the prevalence of HIV infection in persons attending a Sexually Transmitted Diseases (STD) clinic and in order to offer counselling and voluntary partner referral, we instituted a program offering voluntary, anonymous serologic testing of all persons attending the STD clinic. He continued serologic testing by request at the STD clinic and at New Mexico AIDS Services (NMAS). Serum was screened by EIA, and sera positive by EIA were confirmed by indirect flourescent antibody testing. 693 of 1221 patients (52% of 155 gay males, 57% of 662 heterosexual males, and 58% of 404 females) seen from October 1 to December 31, 1986 accepted the test, and 12 (1.7%) were positive. A11 12 were gay males. In contrast, 16 (9.8%) of 163 screened by request at the STD clinic, and 12 (11.7%) of 102 screened at NMAS were seropositive. Of 265 screened by request, 21 were screened for symptoms and 14 because of exposure to a serODOSitive partner. Twelve (86%) of these 14 were seronegative. We conclude that voluntary, anonymous HIV screening is accepted by both heterosexual and homosexual patients attending a STD clinic. Knowledge that a partner was seropositive led to screening and counselling in 5.2% of persons requesting screening, and 86% of these were seronegative at the time of counselling. Voluntary screening of persons attending STD clinics and voluntary partner referral should be considered in areas of low seroprevalence for HIV antibody. THB18" Teaching AIDS: A Resource for High School AIDS Prevention Programs MARCIA QUACKENBUSH*, P. Sargent**, *UCSF AIDS Health Project, San Francisco, CA, **San Francisco General Hospital Department of Psychiatry, San Francisco, CA. The need for resources for high school AIDS prevention programs has been noted by many policy experts. The first professionally published, nationally distributed curriculum for high school students represents an important contribution in this area. The curriculum includes rationales for teaching AIDS to high school students, basic information about AIDS, suggestions for and concerns of teachers, and seven teaching plans. The plans are appropriate for a variety of classes, including family life, science, history, social studies, civics or psychology. THP18 The Centers for Disease Control (CDC) CompUterized Bibliography for ' Information on the Acquired Immunodeficiency Syndrome (AIDS) DEBORAH M. COLLIER, D.P. DROTMAN, T.A. LEONARD, J.W. CURRAN. Centers for Disease Control, Atlanta, Georgia, U.S.A. There has been an explosive increase in the number of requests for AIDS in- formation received by CDC. In the last 2 months of 1986, the Technical Infor- mation Activity office of the AIDS Program, Center for Infectious Diseases at CDC filled 670 requests for journal reprints, responded to 362 letters, and answered 17 telephone calls per day (average). Many more such inquiries are received by other CDC offices. Inquiries come from State and local health agencies, infection control practitioners, clinicians, counselors, Federal and State legislators, a multitude of grass-roots AIDS organizations, and many oth— ers seeking to educate themselves or care for others. Quick access to relevant information is necessary to assist those people in accomplishing their work. One source used to assess what CDC personnel have written on AIDS is the computerized bibliographic retrieval system. One of the databases maintained on this system includes published articles written by CDC staff members on prevention, public health policy, epidemiology, surveillance, and laboratory research. The database also includes 94 AIDS—related articles published in the Morbidity and Mortality Weekly Report. The bibliography can be requested through the Information Resources Management Office, or it can be accessed through any terminal linked to the main CDC computer. Searches can be requested by various parameters (e.g. subject, author, time period, journal). New software for this database will provide easier access and wider application. The new system will be one of the most efficient mechanisms for public health workers, clinicians, and others to document CDC AIDS-related information and respond to important demands. THURSDAY, JUNE 4 HIV Antibody Testing in British Columbia: An 18—month Report MICHAEL L. REKART, Division of STD Control, British Columbia Ministry of Health, Vancouver, 3.0., Canada THP.189 HIV antibody testing has been available in British Columbia since October 7, 1985. An ELISA test is used initially with IFA and Western Blot confirmation. Testing is available through any registered physician and through a government testing, evaluation and counselling clinic in Vancouver. The laboratory requi— sition notes age, sex, date, risk group, physician and geographic location. Results of over 10,000 tests have shown the following prevalences: gay/bisexual males 25%, intravenous drug users 31, heterosexual contacts 1%, hemophiliacs 28%, blood transfusion recipients 1%, and prostitutes 2%. The overall reac- tivity rate was 10%. Samples submitted per month were stable at 1000-500 until 1987 when the number began to rise dramatically. Accompanying the rise in samples submitted the monthly reactivity rate declined from 12-15% to less than 3%. Private physicians submit approximately 601 of all samples followed by hospitals (16%) and the government clinic (15%). Samples from the government clinic have a significantly lower reactivity rate than those from elsewhere, perhaps reflecting a reluctance for those at greatest risk to use the government facility. This testing system has proven acceptable to the medical community, to high risk groups and to the general public. The results have been useful to public health officials. THP190 Strategies for Intervention in Minority Communities ' RALPH J. DICLEMENTE, PhD and CHERRIE B. BOYER, PhD University of California, School of Medic1ne, San Francisco, CA The incidence of STDs among adolescents suggest that the future rate of HIV infection may far exceed its present rate. Data on Black adolescents strongly suggest that they may be at increased risk of HIV infection. A survey of misconceptions about AIDS indicates that Black and Hispanic adolescents were twice as likely than White adolescents to believe that AIDS could be contracted through casual contact, i.e., touching or being near someone with AIDS (p<.Ol). Black and Hispanic adolescents were also more likely to believe that "all gay men have AIDS" (p<.01) and that "all gay women have AIDS" (p<.001). These findings suggest that adolescents generalize from gay men to gay women even though there is no evidence to suggest that this group is at risk of HIV infection. These misconceptions may increase adolescents, particularly Black and Hispanic adolescents' risk of HIV infection by diverting attention from risk behaviors. To dispel these misconceptions requires communicating factual information about AIDS and sensitivity to the cultural and emotional issues which the AIDS epidemic engenders. This requires a systematic public health education effort including school-based AIDS curricula as well as the support and participation of the community-at-large. One strategy may be to train indigenous community members/groups to serve as educational resources, as they may be sensitive to potential barriers that could inhibit receptivity to AIDS information and behavior change. Interventions in minority communities will be discussed. THB191 The impact of information on AIDS: The blood donor perspective A.P.M. LOS*, G. ROLSMA*, L. ACHTERHOF**, TJ. TIJMSTRA*, T.B.P.M. SUURMEYERK C.TH. SMIT SIBINGA**, *Div. of Medical Sociology. University of Gro- ningen, ** R.C. Blood Bank Groningen—Drenthe, Groningen, NL Since 1983 all donors receive information on AIDS and risk factors by circu— lar letter, and since May 1985 on anti-HIV testing. A study was set up to in- vestigate: 1) Adequacy of information, 2) How donors associate with the infor— mation and 3) Impact of information on motivation. Methods: Analysis of donor population in period '83-'87, and a postal questi- onnaire sent to a random sample (500) of the donor population (55,000). Results: 133 persons (115m/18f) terminated blood donation indicating a risk factor. Total donor population increased 72, without any change in demographic composition. The increase did not differ from previous years. From the 133 'risk factor' donors, 18 (13.72) enrolled as a first time donor. These 18 re- present only 0.IZZ of all first time donors registered since April '83. of over 97,000 donations tested since May '85 only 4 (0.004%) were confirmed positive (WB +IF). The results of the questionnaire showed positive attitude, good moti— vation of the donor population and great concern with information on AIDS. However, results show striking discrepancies between aspects of attitude, and cognitive aspects. Conclusion: Combining it seems that the given link with risk factors. that to the majority of not adequately conveyed test results and results of the self-deferral programme information was well received by those who recognise a In contrast, the results of the postal survey indicate our donor population the right emphasis and meaning are by the given information. 195 THPJQZ Randan—digit Telephone Survey for Knowledge and Attitude about AIDS RI_CHARD L. VOGI‘, D. KUI‘ZKO, S. KAPPBL, M. BIDZICEVIC, Vermont Department of —Health, Bur—lington, Vemont. Trained interviewers, using a random-digit dialing system, called 3,650 Venront phme numbers state-wide soliciting both howledge and attitudes about AIDS and HIV transmission. Interviews were cmpleted on 602 Verxmnt residents aged 18 and older. Responses were analyzed by demographic variables, including age, ear and education. Thirty-one questions on the questionnaire which had clear answers were chosem to test the knowledge of those surveyed. Persons with greater education, those who were younger and the male gender tended to answer more questions correctly. Questions answered more correctly by all respondents included those concerned with risks associated with sharing needles (96% correct), male homosexual sex (96% correct) and heterosexual sex (94% correct). Ninety—five per cent of the respondents correctly stated that persons can be infected with the AIDS virus without their knowledge. Questions that tended to be answered incorrectly included those concerning the lack of risk associated with female l‘mvosexual sex (10% correct) and potential risk of virus transmission through breast milk (26% correct). Only 75% of respondents stated that you could not catch AIDS from donating blood. Those surveyed had inconsistent responses on the lack of risk of casual transmission. Ninety—five per cent stated one could not catch AIDS by shaking hands; but only 64% stated that AIDS could not be transmitted through sharing a drinking glass or an eating utensil. Whereas 78% of respondents felt that it was all right for children with the AIDS virus to attend school, only 60% would not be worried about their child catching AIDS from a classmate. ‘I'l'nse surveyed seemed to be knowledgeable about the major risks for infec— tion but less knowledgeable about the lack of risk of casual transmission. "“3193 Anonymous Testing in Public Places: A Social Psychological Examination of the Destigmitization of HIV Antibody rnesting .m*, D. TRIPP*, C. BRIAN”, R. WYEIV", L. LANSKY"*, P. OGG**, mane mnati Health Department, Cincinnati, Ohio, "Psychology Department, The university of Cincinnati, Cincinnati, Ohio A team of social psychologists and public health AIDS program staff designed and implemented the first freely accessible and anonylmus testing offered to the general public apart from the alternate test sites. [hiring a two day health fair condmted in the busy lolby of the Federal Boilding in Cincinnati and at the work site of an Environmental Protection Agency, 225 individuals carpleted questionnaires examining attitudes about AIDS and 84 individuals requested HIV testing. Destigmitization of the test was achieved by positioning it between diabetes and blind pressure screening. This presentation considers issues related to the social psychology of AIDS antibody testing and the factors that need to be (xmsidered in the destigmitization of the test. AIDS hysteria is described as a form of collective behavior in which the public finds itself in an ill defined normative setting. lbutine, anonymous, and wellness—oriented HIV screening is presented as a means of resolving ambiguity and decreasing AIDS hysteria. THP194 The Level of Knowledge and Attitudes Regarding AIDS and HIV Infection in the Nashville, Tennessee Metropolitan AreaH ANGELO GENE COPELLO, M. S. CURVIN, J. S. DYE, R. M. ZANER J. PERKINSH Vanderbilt University School of Medicine, Nashville, TN, ' Meharry Medical College, Nashville, TN. A survey was conducted of the adult Nashville, Tennessee Metropolitan population during September, 1986 to establish the level of knowledge and types of attitudes concerning AIDS and HIV infection. The instrument was developed on the basis of previous studies; it included 8 demographic questions, 22 knowledge-base questions, and b attitudinal questions. Subjects were randomly chosen from the area phonabook and surveyed by trained interviewers. Four-hundred and five subjects participstsd. Comparison of demographics with census reports indicated the sample to be reprsssntative; in particular level of education and racial figurss were highly representative. Three results were considered significant both statistically and for program development in AIDS education and prevention. First, demographic variables statistically associated with the highest level of knowledge about AIDS were general level of education and age. The more educated the subject, the more he or she knew about AIDS; younger subjects knew more about AIDS than older subjects. Second, the difference in level of know- ledge about AIDS between blacks and whites was so slight statistically that it posed no practical implications. And third, a strong statistical association existed between higher levels of knowledge about AIDS and a resistance to sanction employment and housing discrimination against persons infected with HIV. This result supports the importance of general AIDS education programs. AIDS education and prevsntion programs in metropolitan areas with lower caseloads can be assisted in their development by studies of sxisting local attitudes and levels of knowledge concerning AIDS. THURSDAY, JUNE 4 THR195 AIDS and Biomedical Research: E. I. CHATZIANDREOU, M.D., MPH, JOHN GRAHAM, Ph.D., Harvard School of Public Health, Boston, MA. The rapidly expanding AIDS research budget may be exacerbating political pressures to reduce or slow the rate of growth in biomedical research funding aimed at other health impairments. In this paper, we present a framework and method for comparing the size of the AIDS research budget to the size of research budget for Cancer, Coronary Heart Disease (CHD), and Accidents. The framework utilizes information about several measures of the burden of health impairments on society; deaths, early deaths, forgone life years, and medical care costs. The calculations in the paper relate Fiscal Year 1986 budgetary expenditures to projection of disease burden in 1991. We show that these four health impairments are not given equal investment priorities by the Federal Government. Accidents receive relatively little priority; Cancer and AIDS are roughly comparable. The priority assigned to CHD is sensitive to the index of disease burden selected by the analyst. The paper relates these findings to the National Research Council‘s recent recom- mendation of one billion dollars AIDS research budget for 1990. The authors of the paper urge policy makers and scientific institutions to make explicit decisions about the marginal productivity of research investments - against health impairments - that claim limited resources. A Comparative Analysis THR196 An Ethnography of Needle Sharing CLAIRE S’I'ERK, J.FRENGI, New Jersey Dept. of Health, Trenbai, NJ The hypodermic set ("works") has a neaning in the heroin subculture beyorxithatofanedianisntoadiiaveagoal. It isasymbolic reprosentatim of the world of dope. Sharirgandreusingworksalugmdnigusersisasignifioantneans for transnission of the HIV. Street wisdan often dictates behaviors that foster oontimed transmission. Fur exarple, addicts have learned that boiling the works jams the plurger by the siliom lubricant. l-bwever, nuch street wisdcm has little factual foundation, rather serving only socializatim processes. lhecareamimaintenanoeofvnrksservestoperpetuatereuse, asdo users' perceptions of statutes that restrict sale and possession. HIV is transmitted at the slmting gallery, but users' perception of the latter is oanplex. A few galleries provide only rental of works. More sell drugs, only secondarily renting works. Still more provide free access to works fordrugpurchasers. Manyl'msedealersallmsteadycusborerstoborrw worksasaomvenience. Finally, saneusersbecanelqmifortheir willingness to allow friends to shoot up in their hanes. Along this omtinuum, fire risk for HIV transmission is a function of the mmberofusarsirmlvedmsharingarxiflieloosenessofflieparticipant network. Anmxierstandingofuserperoeptiorsandbehavioriscrucialto the developmart of prevention efforts directed toward reducing the spread of the virus through these sharing processes. THP197 'lhe effect of AIDS diagnosis upon close personal interactions among fanily menbers of AIDS patients. 9E FRIEDLAND, P KAHL, C FEINER, M ROGERS, M MAYERS, RS KLEIN, et a1. Montefiore Medical Oenta, Albert Einstein Coll. of Med., Bx, NY, CDC, Atlanta, Ga., USA 'Ib explore the effect of AIDS diagnosis upon behavior, we evaluated the sharing of household facilities and items and close personal interactions among household contacts of AIDS patients before and after the diagnosis of AIDS aid diring two time periods in which availability of information about risk of household transmission differed. 199 IDusehold contacts of AIDS patients were evaluated with detailed standardized interviews to determine the nature and amount of household interactions with tie AIDS patient; The first 104 (group 1) were evaluated from 10/84 to 5/85, the second 95 (grow 2) from 6/85 to 11/86, after information about lack of transmission of HIV infection was known and made available to study participants. The median age of the 2 groups was similar. of the 199, 144 had household contact both before and after the AIDS diagnosis (87 in group 1, 57 in group 2). By McNemar's test for matched pairs, significant decreases in sharing of household items occurred after diagnosis in both groups: combs, towels, eating utensils, plates, glasses. In group 1 measures of close personal interaction decreased significantly after diagnosis: (hugging 78-54%, kissing 86—67%). In the group 2 there was no significant change in these close personal interactions after diagnosis (tugging 76-63%, kissing 65-61%). Despite information allowing lack of risk of transmission anong household members of AIDS patients, significant reduction in sharing of hoisehold items and facilities occurred. Close personal interactions were maintained, however, after information about lack of risk became available. Therefore, Patients and family interactions may be influenced by information dacut lack of transmission. 196 THR198 Beliefs and Behaviors R ardi AIDS: A Surveyiof Street InbavernlsDru Uses ,‘ S. FRIEDMAN,‘ C. E MAlxiE ' D. S. D. C. DES JARLAIS," & W. HOPKINS" 'Narcoflc & Drug Research Inc., NY. N.Y., U “New York State Division of Substance Abuse SansNYN .. .Y. Effective work in helping addicts to engage in risk reduction behaviors will be enhanced by understanding what addicts currently believe about AIDS, and what Iheil relevant behavvors are. Data were collected ha a "street survey" of addicls in one high-drug-use area in each of three New York 'ty boroughs. While most previous reports have studied IV usersin treatment $rams, street users are particularly important as a group lhafloommues frequ I dru use. The Street Research Unit of the New York State Dleion of Substance Abuse rvlces asked openended questions of 137 IV drug users who were unaware that they were being interviewed. Three (waders of these "street addicts" knew that the spread of the AIDS virus is related to drug use and four—fifths relate If to sexual activity. The proportion aware of drug use as a factor is noticeably lower than that reported for a 1984 sample of methadone maintenance treatment dlents (Friedman & Des Jarlais. l986). Slightly over half of the street IV drug users engage in at least one valid protective measure, ver similar to Friedman &.Des Jarlals' comparable proportion. Two-fifths have chang their drug tamer? practices to rotect themselves, while measures relaled to sex were mention by one fifth. hose findings show that although there IS alread conSIderable knowled e and nsk reduction even by street addicts, there are also arge numbers who la Information and/or sufficient motivation to engage In risk reduction behaviors. Efforts to disseminate accurate information about I S to street lV users are likely to result in an Increase in both knowedge and risk reduction practices. Accurate Determination of Risk Behavior in Persons with AIDS. TH2199 ANASTASIA M. LEKATSAS, R. O'DONNELL, J. WALKER, P. THOMAS, New York City Department of Health AIDS Surveillance Unit, NYC, NY. The New York City Department of Health AIDS Surveillance conducts sensitive investigation of AIDS patients denying major risk factors of intravenous drug use (IVDU), male homosexuality, transfusion and, for women, sex with a man at risk. of 270 cases reported monthly, l9 (7%) fail to identify a risk on ini- tial interview. After investigation, AOZ of these cases are found to have en- gaged in IVDU or homosexuality. Of 204 women claiming sex with a man at risk, all knew their sex partners were at risk and could identify them by name. Sixty (29%) were married or common-law to the man. Nineteen (9%) were later identified to be IVDU themselves. Only four (8%) of 53 males claiming female contact were able to identify the women they believed infected them. Three men claiming sex with Haitian women as a sole risk had engaged in homosexual activity. of 47 men claiming sex with female prostitutes, 31 (66%) had engaged in IVDU or homosexuality. Seven of eight health care workers claiming occupa- tional exposure were subsequently identified as IVDU or homosexuals. Our statistics support the epidemiologic benefit of careful case investigation. Interview of AIDS patients or close contacts is psychologically stressful for interviewer and interviewee. Supportative elicitation of highly personal information can represent a catharsis for the individual, who may have signi- ficant motives for denial of risk behavior. This paper addresses issues en- countered in undertaking investigations. Case material provides examples of how to initiate, sustain, make transistions and close a non-identified risk interview while maintaining the utmost concern for the patient's feelings, rights and dignity. THPZO" A Model of Psychosocial Intervention in a Family Practice Center: forpersons ' with Human Immunodeficiency Virus JOYCE PERKINS, T. J. WOOLRIDGE, R.A. FRANCIS, MEHARRY School of MediCine, Nashville, TN, Family Practice Center, Nashville, TN. The Family Practice Center (FPC) of Meharry Medical College has developed a model of psychosocial intervention for patients with Aquired Immune Deficiency Syndrome (AIDS) and other Human Immunodeficiency Virus (HIV) related conditions. The patients served by the center are typically socially and economically disadvantaged with minimal social support and limited access to medical care. All patients diagnosed or suspected being at high risk for AIDS are evaluated by a train— ed AIDS ccunselor usinfitwenty—two page Inventory Assessment Form. Individualized comprehensive treatment plans are then developed to provide patients with emotional, social, medical and economic assistance. In evaluating these patients, it has been found that they and their lovers, family mem— bers and friends are severely stressed. Even persons who are antibody-negative but athigh risk for infection are found to exhibit symptoms indicative of stress. Recurrent psychological themes found are depression, conflict associated with a life threatening illness, feelings of isolation from friends, family and medical personnel, guilt, diminished self—esteem, preoccupation with economic problems and suicidal thoughts. Our experience, following one year of intervention, suggests that individual and group counseling enhances the quality of life for these patients and augments the effectiveness of the medical care delivered. THURSDAY, JUNE 4 THR201 Homelessness in Patients with the Acquired Immune Deficiency Syndrome (AIDS). Catherine Butkus Small, G. Laper, L. Ricci, North Central Bronx-Montefiore Hospitals, Albert Einstein College of Medicine, Bronx, New York. The number of homeless individuals in New York City (NYC) increased from approximately 7,500 to 10,000 from USS to l2/86. Since North Central Bronx Hospital(NCB) serves one of NYC's poorest boroughs, we tried to determine if homelessness was a major problem among our AIDS patients and, if so, how it affected their discharge planning. From 9/85 to 9/86, 87 patients with full-blown AIDS were hospitalized at NCB. Seventy-seven were intravenous drug abusers (lVDA) or their sexual partners; lo were homosexual. Seventy-eight were members of minority groups. Seventy-two (83%) either lived with relatives (68) or had their own homes (Ii). Fifteen (I796) were homeless; Ill/l5 were lVDA; 10/15 (66%) were homeless prior to the diagnosis of AIDS. Of the 15 homeless patients; I; were accepted home by relatives or friends; (i went to hotel rooms provided by the municipal social services department; 3 went to hospices; 3 died; 1 left against medical advice. Although largely lVDAs from indigent minority groups, the majority (83%) of our AIDS patients had family or friends who accepted them within their homes despite their diagnosis. Homelessness is still a problem for a significant number of our AIDS patients (17%) who often have severe social problems unrelated to their diagnosis of AIDS. Discharge planning thus becomes more difficult. THPZUZ Attitudes of Female Prostitutes in London to Barrier Protection. SOPHIE DAY, H Ward, J Wadsworth, JRH Harris. St Mary's Hospital London, UK. Fifty-two female prostitutes were recruited to the anthropological comm ponent of a prospective study of STD and lifestyle at the Praed Street Clinic between 7.86 and 1.87. Female prostitutes are placed in a high risk category for HIV infection but condoms are thought to offer significant protection. Research on the epidemiology and the effectiveness of condoms will have to be considered in terms of their use. Data collected so far suggest:- 1. London prostitutes are predisposed tc use barrier protection in order to avoid contamination with semen itself, as well as possible infection. The entire sample used condoms some of the time with clients at the time of their first visit. 2. This population is also predisposed ESE to use barrier protection with non-paying partners, including pimps. The discrimination provides a critical means of demarcating work from pleasure, and 'punters' from 'partners‘. 3. The women in this group are worried about affecting other prostitutes. This anxiety is related to common ideas about prostitutes as individual sources of infection and a collective pool of infection. Health education has been able to capitalise on tho of these conclusions and the amount of condom tee with clients has risen. However, there has been little change in patterns of use with nonmpaying partners. As this latter group is said to have contact with many other women, this may be a critical avenue for infection. THRzoa Psychological Interventions for Persons With AIDS and Their Part. ners: A Group Approach. JUDY MACKS. MSW, LCSW, University of California San Francisco AIDS Health Project, San Francisco, CA, United States. In this report from the University of California AIDS Health Project, the author will present a group model for working with homosexual and heterosexual couples in which at least one of the partners is diagnosed with AIDS. The author will present case material based upon eight completed groups involving a total of 33 couples. Couples were either self-referred or referred by mental health practitioners. The primary psychological themes presented by each individual and the impact of these issues on the couple will be addressed. The goals of the group include: 1. increasing coping and adaptive skills, 2. increasing independent functioning of the individual and couple, 3. improving communication skills and 4. augmenting social support. Group interventions for medically ill populations including patients with coronary disease, cancer and other life-threatening illnesses have been extensively documented in the literature, as has the impact of the illness on the family. The author will discuss the relevance of this literature in work with this population. 197 THP.204 ABSTRACT NOT AVAILABLE AT TIME OF PRINTING THP205 The Right-to-Know: AIDS—Free International Certificates. ' JOHN R. SEALE, Private Practice, London, England. HIV infection has presented modern medicine with novel chall- enges and e thical dilemmas demanding innovation if its spread is to be controlled within the framework of a free and responsible society. Infected people usually remain infectious, unknowingly, for several years before illness ensues, and they are particularly likely to infect wives, husbands, fiances and infants. People who are ESE infected with HIV have a Right-to-Know. They also have a Right—to—Know that another person with whom they are proposing to start, or continue, a sexual relationship — whether within or out— side marriage - is also 295 infected. All "safe sex" techniques are inconsistent with procreation. The serological tests used to screen blood prior to trans— fusion provide very good evidence of freedom from infection with HIV. This information on a certificate would satisfy the Right— to-Know of individuals and their sexual partners. The certificate must be unforgeable, up-datable, internationallyrecognisable and clearly identifyable as belonging to the owner. Only laboratories approved by public health authorities and WHO should be licensed to test. Active encouragement by governments, WHO, medical, scientific and religious leaders for people to obtain certificates on a voluntary basis will benefit individuals and slow transmission of the virus in the community. The need for the certificates to be regularly up-dated will provide a powerful incentive for responsible behaviour - particularly by young people. 1112206 Medicine in Plague Time: Duty or Virtue? ABIGAIL ZUGER and S.H. MILES, Center for Clinical Medical Ethics, Department of Medicine, University of Chicago Hospitals and Clinics, Chicago, Illinois. The profound reluctance of some physicians to care for patients with AIDS prompted us to review medical responses to analogous historical plagues. No consistent professional tradition emerged. Many historical physicians, including Galen and Sydenham, fled from patients with contagious epidemic diseases. Many of their colleagues remained behind to care for plague victims at considerable personal risk. No formal statement of this duty, however, was enunciated until 1847. This historical ambivalence suggests that an ethic stressing traditional professional duties may not be ideal for defining the optimal relation of the medical profession to patients with AIDS. A new statement to guide the profession in the AIDS pandemic cannot invoke punitive sanctions against physicians refusing to treat HIV-infected persons, for these would violate physicians' civil libereies and personal autonomy. Nor can it be derived from these patients' right to health care, for that is a claim against society rather than individual practitioners. Civil and professional proscriptions against negligence or abandonment apply only to therapeutic liaisons after they are contracted. However, a professional duty to treat HIV-infected persons could be based on the understanding of medicine as a moral enterprise. In this context, treating HIV-infected persons is a virtuous act, that meets both patients' and society‘s health needs and confirms the moral mission of health care. THURSDAY, JUNE 4 THP207 Management of Confidentiality by a Cohort of Gay and Bisexual Men Who have Learned their Antibody Status. JANE S. ZONES‘, D.R.BEESON**, D.F.ECHENBERG***, G.W.RUTHERFORD***,P.0'MALLEY*’* *University of California, San Francisco; ‘*California State University, Hay- ward; ***San Francisco Department of Public Health, California, U.S.A. While much attention has been given to the issue of confidentiality within the research process, there has been little recognition of the difficulties those who are undergoing HIV antibody testing may have in maintaining their own privacy once they leave the research setting. We followed, for an average l0 months, 116 gay and bisexual men who were tested for HIV antibody as part of ongoing epidemiologic studies conducted by the Health Department and the Centers for Disease Control. Of those who chose to learn their antibody status, both seropositives (N=51) and seronegatives (N=36) told an average of 19 of their acquaintances their serostatus. Thosg who chose not to learn their antibody status (N=29) told fewer acquaintances (X=14) about their having been tested and their decision not to find out the results. Several of those inter- viewed noted changes in relationships, either for the better or for the worse, that they attribute to risk status disclosure. Few, however, would change whom they told about their risk status had they the opportunity to reconsider these past decisions. Likewise, if they could choose anew, nearly all stated that they would consent to being tested again as part of the research process. Study participants found disclosure of antibody or risk status to others to be either helpful or neither helpful or harmful. In general, these men have not encountered damaging reactions to disclosure of antibody status in the relatively supportive environment of San Francisco. THP208 Continuous Variables, Discrete Decisions: Determination of Ethically ' Acceptable Risks of False Laboratory Results in Blood Donor Screen- ing. CELSO BIANCO. The New York Blood Center, New York. N.Y. lOOZl The establishment of appropriate "cut-offs" for screening assays in blood banks raises issues that go beyond the technical, medical and scientific community and require the resolution of ethical issues. The problem occurs because: (I) sophisticated assays produce continuous results, e.g. the ELISA for antibodies to HIV produces results from zero to maximum. may miss specific antibodies and detects non-specific antibodies; the cut-off value that separates reactives from non-resctives is arbitrarily defined as the best possible discriminator between populations and presumably normal individuals, and (2) assay results have to be applied without the benefit of clinical evaluations combining medical history, physical examination and laboratory studies. The problem is further complicated by unrealistic expectations of no risk of disease transmission by transfusion, goal that can only be achieved by eliminating transfusions. Risk-benefit assessment can be used in the determination of screening assay cut-offs. Committees comprised of experts, ethicists and recipients could, at regular intervals, determine the maximum acceptable risk for a transmissible disease based on epidemiologic studies. clinical trials, assay characteristics, and curves of risk probability of various cut-offs. Recipients of transfusion would be able to make their own decision based on this information. Insurance carriers would have guidelines for coverage, and the legal system would have means for dealing with litigation and compensation of victims. THPZBQ Issues of Foster Care and HIV Infection in Infants of Drug ' Addicted Mothers. ANN SUNDERLAND', H. MENDEZ’, S. HOLMAN‘, M. BERTHAUD‘, G. MOROSO', S. LANDESMAN', et al. SUNY Health Science Center at Brooklyn**, Brooklyn, N.Y., U.S.A.and National Institutes of Health", Bethesda, M.D., U.S.A. A cohort of 43 babies born to HIV seropositive (SP) and seronegative(SN) drug addicted (DA) women are being followed in a prospective perinatal HIV transmission study. Sixteen of 43 (36.1%) of these are in foster care (FC). There is no difference in incidence of placement between SP(9/16) and SN(7/16) groups. where results are known to the PC system, 3/4 SP babies are in group settings as foster homes are unavailable, including 1 "boarder baby" awaiting placement out of the hospital and 1 child who was abandoned by the caretaker after learning results. Placement of babies tested for HIV raises ethical dilemmas involving confidentiality. A mothers right of confidentiality conflicts with a caretakers right to know results. The latter is needed for proper precautions and appropriate delivery of health care. Informing a PC agency of the serological status of a child born to a SP mother may jeopardize or limit placement possibilities. As fear of AIDS may hinder placement of all babies born to DA women, telling results may enhance SN baby's chance of placement. Informed consent obtained when testing the mother should allow for informing the PC system of the baby's status. our experience and the estimate of 800-1000 SP infants born in N.Y.C. per year points to the need for the FC agencies and their governmental overseers to (1) develop a coherent policy for educating case workers, and potential foster care parents and (2) increase recruitment efforts for foster parents of SP infants. 198 THBZ10 American Corporate Policy on AIDS and Employment BENJAMIN SCHATZ, ESQ., Director, AIDS Civil Rights Project, National Gay Rights Advocates, San Francisco, CA. Survey was sent to "Fortune 1000" companies in October and again in November, 1986 in order to learn approaches of America's major corporations towards employees with AIDS and related conditions. Of 165 companies which responded non-anonymously, 165 (100%) indicated they provide health insurance benefits to employees with AIDS or ARC, 164 (99.5%) indicated that they do not test employees or job applicants for HIV antibodies, 109 (66%) declared that it is their official policy to forbid employment discrimination against employees with AIDS or related conditions, and 33 (23%) had developed or are developing written policies on AIDS. In addition, several companies indicated that they have provided educational materials and programs about AIDS to their employees. Results are significant because they reveal higher-than— previously—estimated degree of proactive response by major employers to the AIDS epidemic. It is hoped that survey findings will encourage other employers, as well as government agencies, to develop compassionate, legally sound policies towards employees and applicants with AIDS and related conditions without fearing that they will be going out on a limb to do so. THP.211 ABSTRACT NOT AVAILABLE AT TIME OF PRINTING THP_212 HIV Seroprevalence Among Nurses Caring for Children with AIDS/ARC MARY BOLAND. J. KERESZTES, P. EVANS, J. OLESKE. E. CONNOR Children's Hospital of New Jersey (CHNJ) & UMD-NJ Medical School. Newark, NJ Sera from 45 female nurses caring for children with AIDS/ARC at CHNJ was tested for HIV antibody. The nurses were volunteers who anonymously completed a questionnaire designed to define type of patient contact and to identify HIV 1nfect1on risk factors. Nurses worked in the following areas: ICU (l4); medical-surgical units (26); ambulatory service (2), and AIDS program (3). 26 (56%) of the nurses cared for patlents for over l2 months for an average of 8-12 hour shifts/month (O-lS shifts). Nurses reported the following types of contact: bathing (41/45), feeding (41/45), care of central venous catheters (42/45), administration of oral and 1ntravenous medicat1on (40/45). obta1n1ng and handling specimens (e.g. blood. urine, stool) (45/45), contact with blood gnd segretions (eg diaper changes) (43/45) and touching and comforting a child 43/45 . The nurses reported following standard hospital infection control procedures sometimes 4 (9%), usually 25 (25%). and always l5 (32%). 3/45 nurses reported needlesticks and 2/45 reported nucous membrane or broken skin contact with a child's blood. 43/45 nurses were healthy. l/45 had the diagnosis of chronic Espteln Barr Virus infection; l/45 had contact dermatitis of the hand that re- quired periodic use of steroid cream. 3/45 had received blood transfusions within the past 5 years. All denied nonprescrIption drug use and all were heterosexual. l/45 had a sexual partner who since developed AIDS. and l/45 reported a present partner who is HIV positive. 100% (45/45) nurses were HIV negative by ELISA and Western Blot. Annual re-testing is ongoing. Data from this study suggests that risk of transmission of HIV during nursing care of children with AIDS/ARC appears to be small. THURSDAY, JUNE 4 THE213 Attitudes Concerning AIDS: Relationship to Behaviors of Dental Health Professionals W V. BADNER‘, B. MAGUIRE‘. ‘UCSF School of Dentistry, San Francisco, CA. To determine AIDS patients’ access to dental care, a randomized survey of dental health professionals in California was conducted. Respondents‘ attitudes, knowledge, and behaviors regarding patients with AIDS and at-risk for AIDS were assessed, as well as the number of patients they perceived to be at-risk for AIDS in their practice. Usable responses were obtained from 297 dentists, 128 hygienists, and 177 dental assistants. Use of infection control was more closely related to attitudes than to knowledge in all three professional groups. When compared with practitioners who thought few of their patients were at~risk for AIDS, those who perceived more of their patients to be at risk had more positive attitudes (p<.004) and were more likely to practice infection control (p<.0001) and to screen patients for AIDS by taking a thorough medical history (p<.02) and sexual history (p<.04). The authors conclude that attitudes toward AIDS, particularly perception of the number of patients at risk in one's practice, affect the screening and infection control procedures used by dental health professionals. Attitudes. rather than knowledge, should be targeted in education programs designed to improve AIDS patients' access to dental care. Creation of a Dedicated Unit for AIDS & HIV—Related Illnes (HIV Patients) at Bellevue Hospital- Impact on ICU Utilization, Care Patterns of Critical Patients & Mortality LOIS BRAUNSTEIN, R. HOLZMAN, J. RIVERA, M. SEIDLIN, Bellevue Hospital Center, .New York, N.Y. A designated unit (12E) for HIV patients with 10 private rooms was created in January, 1986 to concentrate nursing care for acutely ill, non-intubated patients and provide an alternative to ICU for these patients. We studied the 278 admissions during the 6 months prior to the opening of 12E ('Pre') and the 298 admissions during the 6 months following it‘s opening (‘Post'). During this period the average daily census of HIV patients was 46.6 (range 37-55). 133 admissions were excluded because they spanned the transition period. The proportion of HIV admissions who spent time in ICU, 15%, and the mean length of stay (LOS) in ICU, 7.5 days, did not differ significantly between the two periods. Mortality of ICU admissions was 53.5% during both periods compared to 30% for 12E admisions and we for all HIV admissions. Mean LOS in the ICU ftx patients who died was 10 days in conmst to 4.7 days for those who survived. Mean LOS on 12E was 8.6 for patients who died and 12.4 for those who survived. It is notable that the LOS of patients in ICU who died is longer than that of those who lived while the reverse is true for 12E. This may be attributable to the fact that patients in respiratory distress who elected not to be intubated were often admitted to 12E where their deaths were not prolonged by mechanical ventilation. We conclude that the creation of a dedicated unit did not alter ICU utilization or overall. mortality for HIV patients. Instead, it offered a setting in which acutely ill, non-intubated patients could receive a higher level of nursing care. This relieved the burden experienced by the general medical wards and provided a humane alternative for critically ill patients who chose not to undergo intensive care. THP.214 THP215 Absence of HIV Antibody Among Dental Professionals, Surgeons, and Household Contacts Exposed to Persons with HIV Infection. SCOTT HARPER, N. FLYNN, J. VAN HORNE, S. JAIN, J. CARLSON, S. POLLET, et a1. Univ. of California, Davis, Sacramento, CA. Dental professionals and surgeons have increased risk of acquiring hepatitis B through professional contact with this virus, raising the question of transmission ('1') of HIV in the same manner. Close household contacts of HIV-infected individuals (HIV-I) have not been shown to be at risk for T of HIV. To examine these hypotheses we tested 300 Sacramento and L.A., CA dentists, hygienists, and chairside assistants (who experienced approxi- mately 200 or more exposures to HIV-I), 25 surgeons who operated on HIV-I (usually unaware of HIV infection) and 20 household contacts of HIV-I, for antibodies to HIV by ELISA and Hestern blot techniques. An additional 700 dentists from major U.S. cities will be tested prior to presentation of this data. Subjects were asked not to participate if they had any other recog- nized risk factor(s) for HIV exposure. He also questioned dental profes- sionals regarding gloving practices and frequency of accidental puncture wounds. Dentists and chaireides seldom wore gloves, whereas hygienists wore them for the majority of procedures. ”25 reported 22 puncture wounds per month, 25} had >6 per month. No subject. had antibody to HIV by Western blot analysis. He conclude that risk of ’1' of HIV to dental professionals in Sacramento is small. Our small numbers or surgeons and household contacts provide additional evidence that T of HIV in these settings is rare. 199 THR216 Hepatitis Delta Antigenemia 1n Intravenous Drug Abusers with AIDS: Potential Risk for Health Care Workers MARY JEANNE KREEK", D. DES JARLAIS", C. lI'REF‘O'W", D. NOVICK"'*, A. QUADER",J. RAGHU'NATH‘, 'Rockefeller University,*“NY State Division of Substance Abuse Services, ****Beth Israel Medical Center, New York City, USA, *"Faculte Alexis Carroll, Lyons, FRANCE Intravenous drug abusers (DA) are the second largest group at risk for infection with HIV and developing AIDS (25‘ of U.S. cases). DA are also a major risk group for infection with hepatitis B virus (HBV): over 80‘ of heroin addicts have some marker of HBV infection. Hepatitis delta virus (MN) is a defective RNA virus which can replicate only in the presence of repli- cating HBV. The prevalence of HDV infection, which can cause fulminant hepatitis and death, or rapid progression to cirrhosis, has been increasing in DA. This study was conducted to determine the prevalence of markers of HDV infection along with HBV markers in a group of unselected DA entering or in treatment and, in a group of DA with AIDS disease and to examine the relationship of immunosuppresslon in AIDS on the expression of HDV infection. Subjects(N) Positive Test: HBSAg HDAq anti-HDV PDA 347 18 ( 5.2‘) 2 (0.6‘) 104 (30.0‘) PDA with AIDS 53 8 (15.1%) 3 (5.7%) 0 ( 0‘) The overall prevalence of HDV markers was 27.3‘ in DA subjects. Delta antigenemia, associated with infectivity, and usually detected only in the first 2 weeks of delta infection, was found in a significantly increased number of DA with AIDS, probably due to either a persistence or reappearance of antigen in the setting of AIDS related immunoeuppression. HBV vaccination to protect against HBV and HDV infection is recommended for all persons working with blood from patients with HIV disease. THR217 JEANNEE PARKER MARTIN, Director, AIDS Home Care and Hospice Program, San Fran- cisco, CA. In 1984, Hospice of San Francisco developed the first AIDS Home Care and Hos- plce Program in the country. This program has provided care for more than 500 AIDS/ARC patients at home. Increasingly, needs for 24-hour attendant care and supervision have been identified. Consolidated housing alternatives were established to help meet this need but were inadequate. In March 1987, Hospice of San Francisco will open Coming Home Hospice, a res— idential board and care facility for terminally ill persons with AIDS and ARC. This facility will allow 15 patients to receive comprehensive hospice services 24 hours a day. These services will be provided by Licensed Vocational Nurses, attendants, volunteers, Registered Nurses, and Social Workers. This presentation will highlight the unique characteristics of Coming Home Hospice, its Advisory Board, community support, and public and private funding sources . Coming Home Hospice: A Model Residential Hospice Alternative THEZ18 A Model for AIDS Professional Education JEFFREY §; MANDEL, PHD, MPH, M. GRADE PHD, L.S. ZEGANS, H. BARTNOF, MD, B. FALTZ, RN, J.L. ZIEGLER, MD, et a1., UCSF School of Medicine, San Francisco, CA, USA A model has been developed specific to the education of physicians and nurses, in practice and in-training, at the University of California, San Francisco. Over a 3-year period, under federal contract, 5000 health practitioners will be comprehensively educated via this mode]. Curricula have been fashioned with sensitivity for HIV- related diseases as medical illnesses, as the topic of extensive research, and as diseases of unprecedented psychosocial and legal/ethical complexities. The model extends beyond traditional educational frameworks; it addresses the dilemma of how to impart both technical and provocative information in such a way that it is not only assimilated but applied. An emphasis on diagnosis and treatment is matched by that placed upon prevention and health education. The numerous organizational challenges of AIDS professional education are reflected in this model; attention has been paid to interdisciplinary issues and related concerns about professional domain, interagency cooperation, and the integration of community issues into the academic arena. In keeping with epidemiologic trends, both curricula and core faculty reflect the special concerns of third world persons, substance abusers, recipients of blood products, women and children. MD, THURSDAY, JUNE 4 Identifying Major Concerns of Patients with AIDS THR219 CHRISTINE GRADV,J. JACOB, B. BAIRD, J. SPROSS*, V. OSTCHEGA. National Institutes of Health, Bethesda, Maryland, *Massachusetts General Hospital. A descriptive study was conducted to identify and categorize major concerns of individuals with AIDS. Thirty adults were interviewed. The majority were male homosexuals with Kaposi sarcoma undergoing experimental therapies. In— formation gathered included impact of the diagnosis, major concerns, support networks,and persons and actions perceived most helpful. The majority (66%) were told the diagnosis by a physician in person. and (30%) were told over the telephone. The most common reaction was shock or disbelief but 13% expressed relief and 7% expressed feeling "empty" or "dead". Eighty-three percent initially discussed their diagnosis with a lover or friend, while 10% first told a family member(s) with 77% responding in a manner perceived to be helpful. Helpfulness was described most frequently as keeping the relationship intact without significant change. The predominant concern expressed was personal health and continued functioning followed by uncertainty about the future, fear of death and completing research require— ments. At the time of the interview 47% reported feeling always hopeful and 10% never hopeful. Ninety-seven percent reported some uncertainty, 90% fear, 90% fatigue, 97% sadness and 83% anger. Seventy-seven percent of the patients reported never feeling abandoned. From participation in research 23% hoped for a cure, 23% a treatment or experimental drug, and 23% maintenance or prol gation of function. Twenty percent expected no help for themselves but participated to help others. Study information also provides understanding that gives direction to the planning and provision of quality care to this patient population. THRZZ“ MULTIDISCIPLINARY APPROACH TO AIDS PATIENTS. POLICIES AND PROCEDURES IN A COMMUNITY HOSPITAL. L. Andrews, R.N., S. Patronik, R.N., K. Hryb, E. Cooper, M.D., J.J. Klimek, M.D., Hartford Hospital, Hartford, CT, USA. Ours is a 1,000 bed community teaching hospital in central CT where 1 to 4 new AIDS cases are treated each month. In response to increasing needs within our hospital, a Multidisciplinary Committee (MC) was formed to address patient care and staff issues. MC is comprised of representatives from Epidemiology, Social Service, Nursing, Home Care, Pastoral Services, Microbiology, and Rehabilitation. MC functions as an educational resource, and attempts to identify and anticipate problems and share solutions. Members are notified of the admission of an AIDS patient, confidentially, in writing by the Section of Epidemiology. Bimonthly meetings are held during which issues are discussed, policies are established, and individual patient cases are reviewed. Specific patient problems and their solutions are addressed by a team with representatives from each discipline. Educational needs within the hospital are met through inservices to all departments on a regular basis. The MC functions in conjunction with the Infection Control Committee and the Hospital Administration to anticipate and identify the needs of our institution. Collaboration with other state hospitals allows further sharing of problems and solutions. As our number of AIDS admissions increases, this collaborative approach utiliz— ing a variety of departments has worked well. This committee was comprised solely of representatives from within our institution and did not require ad- ditional funds or outside resources. The MC model may be useful for handling small to moderate numbers of AIDS admissions in a community setting, where resources are limited. THP221 Costs of AIDS to a Public Hospital. ' GERI_R_§R_I3_wu*. T BRANDESH. c HALEYMt. GB semen“. HALEYi. R ANDERSDNarl. *Uniy Tx HSC—Dallas, **Dallas County Health Dept, *rrParkland Mem Hosp (PMH), Dallas, TX Since all AIDS cost studies have been based on patient charges rather than true hospital costs, and since public hospitals have fixed budgets. this study intends to determine the marginal costs of AIDS to PMH. From 1992-86, 168 persons with AIDS were admitted to PMH. accounting for a total of 252 admissions.* The number of admissions increased from 5 in 1982 to 134 in 1986. The total charges were $37,312 in 1982 and rose to $l.k5 million in 1986. Marginal costs were determined by adding the cost components for labor (nursing, housestaff, and social work), ancillary services, dietary, pharmaceuticals. supplies. and laboratory. Estimates for nursing labor were based on standard patient care units assigned to each patient and for housestaff labor on progress note frequency. Total inpatient costs rose from $15,000 in 1952 to $1.03 million in 1936. The costs per admission peaked in 1964 and then declined due to a shorter mean length of stay: the mean stay was 22 days in 1984 and IE days in 1985. The mean daily charge declined from $1,109 in 1984 to $872 in 1986. However the mean daily cost rose from $579 in 1989 to $719 in 1986. 14% of charges to AIDS patients were paid. compared to 31% of charges to other patients. AIDS has a substantial impact on the economics of public hospitals that reouires major efforts at economic and epidemic forecasting to adapt the tax base to increasing case loads. *1986 data are estimates pending final analysis.. R 200 THRZZZ The Nurse Role in an HIV Diagnosis and Management Centre Patrick M. Turbitt, Andrew Morlet, Julian Gold, Albion Street (AIDS) Centre, Sydney Hospital, N.S.w., Australia. The Sydney AIDS clinic was established by the state government in March 1985 to provide free, confidential testing and management for persons infected with HIV. Over 6,000 people have presented for testing of whom 750 were HIV antibody positive. All HIV antibody positive persons are offered ongoing medical management, receive psychological assessment and counselling and return to the clinic for further T-cell testing and review every three to six months after initial diagnosis. The nurse role in this context has developed to include the assessment of new clients to triage them into medium/high and low risk categories according to their likelihood of infection. The nurse collects demographic and extensive lifestyle data from those in the moderate/high risk group before referring for medical examination and counselling. The low risk persons are managed by nurses without referral. Nursing staff are the first line contact for all clients entering the clinic, thus providing an important role in imparting factual, comprehensible information to allay fears and educate those who perceive themselves to be at risk. Nurses are also called upon to provide information to other health care professionals and to conduct in—service training. Whilst the majority of HIV antibody positive clients are at the early stages of infection and require minimal clinical management, the nursing staff offer advice on maximising health, prevention of concurrent infection and reinforce safe sex practices. THR223 Update: Prospective Evaluation of Health—Care Horkers Parenterally Exposed to Blood of Patients Infected with Human Immunodeficiency Virus. RUTHANNE MARCUS AND THE COOPERATIVE NEEDLESTICK SURVEILLANCE GROUP, Centers for Disease Control, Atlanta, GA, USA- As of September 15, 1986, 1,116 health—care workers (HCHs) with documented exposures to blood of human immunodeficiency virus (HIV)—infected patients were enrolled in a surveillance project to determine the risk of occupa— tionally acquiring HIV infection. chs have been followed for a mean of 20.7 months. Percutaneous exposures to blood accounted for 77% (n-856) of the incidents. Exposed HCWS included 679 nurses, l86 physicians, lll laboratory workers, 68 phlebotomists, and 72 others. Exposures occurred in patient-care wards (59%), intensive—care units (20%), operating rooms and morgues (10%), laboratories (7%), and emergency rooms (4%). Exposures judged preventable included recapping used needles (17%), improperly disposing of used needles (13%), and contaminating open wounds (10%). HIV—antibody testing has been performed on serum samples from 716 (64%) exposed HCWs. Two hundred five HCHs with both acute-(Sfio days postexposure) and convalescent- phase (>90 days postexposure) serum samples tested for antibody to HIV were exposed to patients who meet the Centers for Disease Control's surveillance definition of AIDS; one (0.5%) has shown evidence of seroconversion. An additional 47 HCWs with paired serum samples were exposed to HIV—infected patients that did not meet the CDC definition of AIDS; none of these have seroconverted. We conclude that l) at least 402 of injuries in this project might have been prevented by use of recommended infection control measures; 2) the risk (0.5%) of occupational transmission of HIV infection from patients with AIDS (CDC surveillance definition) is low (952 CI 0.00-2.30); and 3) the risk of infection from other HIV—infected patients warrants further examination. THEZZ4 AIDS-HIV Educaflon for Medlcal. Nurslng, and Pharmacy Students at the UCSF School of Medlclne HARVEY S. BARTNOF MD, UCSF School of Hedlclne. San Franclsco. CA Health care provlder students may be thrust Into cllnlcal lnferacflons ulth HIV-Infected paflenfs prlor to recolvlng education on HIV and AIDS. Thls may lead to unecessary Infection control behavlors and phoblns of paflenfs with AIDS and ARC. This may be true especially at UCSF because San Fronclsco has the hlghest denslfy of AIDS cases of any U.5. clty. In order +o obvlafa fhls problem, a multldlsclpllnary survey elecflve course was deslgned and named, "AIDS-HIV l987: Overvlev and Update." The course was modeled after a slmllar experlmonfal course chalrod by fhls author In the Spring quarter of I986. A needs assessment of nadlcal students, course evaluaflon forms from the Sprlng course, and Input from varlous UCSF AIDS researchers and cllnlclans led to the currlculun deslgn. The Course Is thirteen hours In length, lncludlng eleven lecture hours and 2 hours of panel dlscusslons. Lecturers Include nlnotoan UCSF AIDS researchers and cllnlclans. The Course lecture foplcs are: 'Overvlel and lntroductlon;" "Epldenlc Perspscflves and Treat-ant lssues;' "Immunology. Lab Tests, and Autolmmunlfyz' ”Vlrology and Vacclno Horlzons;' 'Cllnlcal Manlfesfaflons of AIDS;' 'ARC;' 'Neurologlc Manlfesfaflons;' "Oral Hanlfesfafié "Transfusion and Blood Banklng;' 'Pedlafrlc Hanlfostaflons;' 'Holophlllacs and AIDS;' 'Psychlatrlc/Psyohosoclal Issuas;" 'Honen and AIDS;' “Ethnlc Mlnorltles and AIDS;' 'Infocflon Control;' 'Healfh Care Provlder Issuesz' "Legal Issues;" "Public Pollcy;" and 'thlcs.‘ The fro panels Include: "Persons with AIDS and ARC;' and "San Franclsco Systems of Care.‘ Pre- and post-course knowledge and aftlfude guestlonnalros ulll he used to assess the success of the Course. The Sprlng Course led to decreased phoblas and Increased knolledge on HIV. THURSDAY, JUNE 4 THP.225 ABSTRACT NOT AVAILABLE AT TIME OF PRINTING THRZZG Inmunologic Reconstitution in AIDS Employing 3‘-azido-3' deoxythymidine and Syngeneic Bone Marrow Transplantation H. CLIFFORD LANE, H. MASUR, J. KOVACS, R. STEIS, M. MEGILL, A.S. FAUCI, et a ., ationa Institutes of Health, Bethesda, MD. The inmunologic defect in AIDS is characterized by a decrease in the absolute number of helper/inducer T lymphocytes and an inability of the remaining cells to proliferate in vitro in response to soluble protein antigens. Bone marrow transplantation and the adoptive transfer of syngeneic lymphocytes employing identical twin pairs where one has AIDS and the other is HIV negative have accomplished only a transient improvement in immunologic function, presumably due to the destruction of the new immune system by HIV. The present study was designed to determine the effects of combining anti-retroviral therapy with 3'azido-3'deoxythymidine (AZT) with adoptive immunotherapy and bone marrow transplantation. Patients were selected for the study if they were culture positive for HIV (with or without clinical illness), demonstrated inmunologic defects characteristic of HIV infection and had an identical twin with a normal inmunologic profile and no evidence of HIV infection. Patients were treated with 500mg AZT q4h for the 12 weeks prior to bone marrow transplantation. At week 10 of AZT they received 4 infusions of peripheral blood lymphocytes from their identical twin, at week 12 of AZT they received 2 infusions of peripheral blood lymphocytes from their twin and at the end of week 12 they received the bone marrow transplant without conditioning. Following transplantation patients were randomized to receive either 100mg AZT or placebo q4h. At the present time 12 patients have entered the study and 4 bone marrow transplants have been performed. While it is still too early to assess the effects of this therapy it is hoped that the data generated over the next 4 months will allow an evaluation of the efficacy of anti-retroviral therapy with bone marrow transplantation in patients with HIV infection. THP_227 Suranin-Imuthiol Combination Therapy of Patients with AIDS- 1 elated 1 x (ARC) Resulss in 6 cases3 1 1 H. TAELMAN, S. SPREO-IER, 0.TEIRLYI€K, M.mERTS, P.GIGASE, P.PIOT . . Institute of Tropical Medicine, Antwerp, Belgium. 2 Institut Pasteur, Brussels, Belgium. 3 C.Heymans Institute, Ghent, Belgium. Previous studies have shown us that suramin, despite its effectiveness as a HIV inhibitor, is unable to improve the immune and clinical status of patients with AIDS or ARC. We therefore started with a clinical trial com- bining suramin with diethyldithiocarbamate (Imuthiol) a drug with inmuno- regulatory properties in 6 patients with ARC. They all had initially lymphocyte cultures positive for HIV markers (HIV antigens and/or RT activity). Once the cultures became negative, suramin lg 1V every 2 weeks together with Imuthiol 10 mg/kg per as once weekly were administered for at least 16 weeks. Each patient was examined clinically and questioned for side-effects of drugs. Plasma suramin levels were determined by HPLC before each new administration of suramin. The inmune status of the patients was screened every 2 months for lymphocyte subsets and for cutaneous delayed hypersensitivity with 7 recall antigens (Multitest). After 16 weeks of treatment,despite maintenance of plasma suramin levels 2 1ooug/m1, there was no change of the clinical status of the patients and no improvement of X or absolute nb of T4 cells or skin tests score was observed. Che patient develop.ed adrenal insufficiency. 201 THEzza Ansamycin (Rifabutin), an Inhibitor of HIV in vitro, Crosses the Blood-Brain Barrier DAVIDSON*, F.P. SIEGAL*, R.A. REIFE*, K. GEHAN*, H. BURGER ’ B. , R. ANAND***, 7“~Long Island Jewish Medical Center, New Hyde Park, NY, 7*‘«'~‘SUNV/Stony Brook, Stony Brook, NV and ***CDC, Atlanta, GA, USA. Current data indicate early involvement of the central nervous system by HIV; progressive encephalomyelopathy (HIV-EM) appears to be an exceedingly frequent complication of late HIV infections. The ultimate utility of candidate virustatic agents will probably depend on their ability to traverse the blood- brain barrier. Ansamycin (ANSA) (Rifabutin, LMh27, spiropiperidyl rifamycin), a semisynthetic derivative of rifamycin S, inhibits HIV in Vitro at concen- trations greater than 5-10 micrograms/ml. ANSA was employed in an open-label clinical trial involving subjects with case-defined AIDS or HIV-EM, to deter— mine toxicities and potential utility at doses greater than those employed for treatment of M. avium-intracellulare infections. Sera ”spiked” with ANSA and its major 25-desacetylated metabolite, LM565, were heated to inactivate HIV (56°C, 20-30 min) without affecting drug detectability by high-pressure liquid chromatography (HPLC). Sera collected serially and CSF obtained after several weeks' oral dosing (300-600 mg/day) were assayed using a modification of an HPLC method established by Adria Laboratories. Both ANSA and LM565 were present in sore, but only ANSA was found in CSF, at levels 30-AOZ of those in serum. These studies indicate that ANSA traverses the blood-brain barrier, across clinically uninflamed meninges,fulfilling an essential requirement for drugs considered for the treatment of HIV infections. THPZZQ Open Trial of Azidothymidine (AZT) in AIDS Patients at Parkland ' Memorial Hospital (PMH), Dallas, Texas DANIEL J. BARBARO*, T. EMANUELE**, L. FREDENBURG**, J.P. LUBY*. *University of Texas Health Science Center at Dallas, Southwestern Medical School, Dallas, TX, **Parkland Memorial Hospital, Dallas, TX. Forty patients have been enrolled in an open, uncontrolled trial of AZT at the AIDS Clinic (PMH). 0f the 40 enrolled, there have been 7 deaths. Two deaths occurred during the week treatment was to have begun and 5 died during the first 3 weeks of therapy. Deaths were due to opportunistic infection or neurological deterioration. Six patients developed opportunistic infections diagnosed after at least 6 weeks on AZT. Three patients developed Pneumo- cystis carinii pneumonia and the other 3 have been diagnosed with Mycobacte— rium avium—intracellulare infection. One patient dropped out of the study because of intractable nausea and vomiting and another was lost to followLup. The remaining 25 patients taking AZT are either clinically stable or improved. Of 20 patients taking AZT for a least 1 month, there has been an average weight gain of 4 lbs. Side effects have been numerous and include nausea and vomiting in seven. Six of these seven improved after lowering the dose. Maculopapular/follicular skin reashes were seen in 5 patients. Two patients developed convulsions on the drug. Laboratory abnormalities have included unexplained, significant drops in the hemoglobin level of 4 patients who have required intermittent transfusions. Six patients had decreases in granulocyte counts requiring dosage adjustment, including one patient whose count fell soon after the initiation of acyclovir therapy. AZT represents a significant advance in AIDS therapy. but its administration is not without problems. THP230 Progressive Histopathology and Prognostic Value of Sequential Lymph Node Biopsies in Patients with AIDS and ARC. Ag: CDADBURN*, C. Metroka**, J. flouredien*. *The New York Hospital-Cornell Medical Center, New York, New York and **St. Luke's/Roosevelt Hospital Center, New York, New York. The prognostic value of progressive lymph node histopothology was studied in 66 sequential lymph node biopsies (bxs) from 27 male patients (2 to 6 bxs per patient) with the Acquired Immunodeficiency Syndrome (AIDS) or AIDS-related complex (ARC). Initial bxs revealed four patterns: explosive follicular hyperplasis (EFR) in 17; mixed BER and follicular involution (H) in 5; follicular involution (F1) in 4; and lymphoid depletion (LD) in l. Lymph node histology showed a progressive loss of follicles and lymphocytes corresponding to a temporal pattern of change; EFE to H to PI to LD. Overall 18 of 27 patients (671) progressed to different histologies on repeat biopsy. On second bx of those 5 initially with H, 3 progressed; 2 to F1 and 1 to LB. 0n the second bx of those 4 initially with FT. 3 progressed; l to LB and 2 to lymphoma. This progressive histologic pattern of change correlated with a deteriorating clinical course; there was an increased incidence of developing opportunistic infections (01), Kaposi's sarcoma (KSL and lymphoma (L) and decreased mean time of survival. of the 18 patients with progressive lymph node histology 15 died (831). of patients with F1 or LD on first or second bx, 921 had or developed 0!, KS, or L and died with a mean survival or 11.5 months. However, only 501 of those with EFH or M on first or second bx had these diseases and died, mean survival of 29.8 months (p-0.01). Sequential lymph node biopsiel may be prognostic of the clinical course in AIDS and ARC. THURSDAY, JUNE 4 THP231 Successful Chemoprophylsxia for We“: sari—nu} pneumonia ' with Dapsone in Patients with AIDS and ARC MLW. H. Lange, N. Braun, H. O'Sullivan, ll. Josefberg, D. Jacobus. St. Luke' s/Rooscvelt Hospital Center, New York, New York. In an open study to evaluate the efficacy of dapsone for the prevention of Eggggggyggi; ' pneumonia (PCP), we studied 156 patients who were at high risk for PCP from14/85 to 1/87. The groups included patients with a prior history of PCP, other life-threatening opportunistic infections (OI), AIDS— related Kaposi's sarcoma (KS), generalized lymphadenopathy, ITP, and malignant lymphomas. All patients initially had less than 200 14+ cells/mm3. Only 1 patient receiving 25 mg po qid of dapsone developed PCP. This patient was also receiving ansamycin for disseminated MAI. Since ansamycin is a derivative of rifamycin and rifamycin lowers serum dapsone levels 7 to 10 fold, it is possible that anaamycin may have similarly affected dapsone levels. In contrast, 1A of 19 patients who refused treatment with dapaone and who were clinically matched with patients in this study developed PCP. Dspsone administration led to a decline in red cell mass, a rise in serum LDE, and the development of methemoglobinemia. 39 patients required one or more transfusions of packed red blood cells. However, temporary discontinuation of dapsone in 11 patients decreased the transfusion requirement but did not eliminate the need for repeated transfusions. Complications included nausea (2) and skin rash (6). Eight patients with ARC or AIDS developed KS while receiving dapsone. By itself, dapsone did not cause significant regression of any skin lesions and did not prevent the development of new lesions. 55 patients developed other life-threatening 01's or malignant complications; 36 of these patients have died. In summary, dapsone is well tolerated and highly effective in the prevention of PCP. THP232 Long- term Follow-up of Fansidar Prophylaxis for Pneumocystis carinii Pneumonia (PCP) in Patients With AIDS. DAVID HARDY, P.R. WOLFE, M.S. GOTTLIEB, S. KNIGHT, R. L.S. YOUNG, UCLA School of Medicine, Los Angeles, CA. PCP continues to be the most common opportunistic infection diagnosed in AIDS patients. While therapy with either trimethoprim—sulfamethoxazole (T/S) or pentamidine is successful in 80 to 90% of episodes of PCP, recurrence rates without prophylaxis remain between 30—50%/year. An increased prevalence of adverse reactions to T/S among AIDS patients often complicate use of this agent as prophylaxis for PCP. We report 11 month (range 2.5—27) follow—up of 60 patients recovered from an initial episode of PCP given Fansidar (20:1 sulfadoxine+pyrimethamine) dosed 1 tablet/week. While 50/60 patients experienced adverse reactions to T/S (rash, leukopenia or GI disturbance) only 6/50 developed rash on Fansidar. No episodes of Stevens—Johnson syndrome were observed. Bronchoscopy with TB biopsy was done in 12/60 patients due to respiratory symptoms. PCP was diagnosed in 5/12 but not found in 7/12 (2 KS, 2 bacterial, 2 CMV, 1 no etiology). Plasma sulfonamide levels done in 3/5 patients with recurrent PCP were undetectable. No hematologic, hepatic or renal toxicity was noted in any patients. We conclude that Fansidar prophylaxis significantly reduces the recurrence of PCP in AIDS patients and appears to be well— tolerated in the majority of patients with previous adverse reactions to T/S. MITSUYASU, THP233 An Antiviral Trial of Rifabutin in Patients with ARC. H. BURGER", B. WEISER", S. NEFF", K. GEHAN"*, R. ANAND***, F.P. SIEGAL**, *SUNY, Stony Brook, NY; '*Long Island Jewish Medical Center, New Hyde Park, NY; ***CDC, Atlanta, GA. We are evaluating rifabutin (ansamycin, Adria Labs), a rifamycin s deriv— ative,as a therapeutic agent for HIV infection in patients with ARC. Rifabu- tin was selected as a candidate drug for this phase I-II study because it in- hibits HIV replication EB vitro, enters the central nervous system (B. P. Davidson et a1 abstract this meeting), has minimal toxicity in AIDS patients treated with low doses for E. avium complex, and is taken orally. We are treating HIV culture positive ARC patients with escalating doses of rifabutin. Virologic response is measured by monthly co-cultivation of patient peripheral mononuclear cells (PMCs) with normal donor PMCs. A signi- ficant increase in the time interval to positive reverse transcriptase activ- ity post-treatment compared to pre-treatment is interpreted as a decrease in circulating HIV titer. We have treated 5 patients with a low daily dose of 450 mg and have followed them for 6—12 weeks clinically, immunologically and virologically. None of the patients treated at this initial dose showed any toxicity or change in clinical, immunologic or virologic status, but the serum levels at 450 mg are below the £2 vitro effective doses. We have therefore recently increased the dose to 600 mg daily on the 2 patients who showed no antiviral effects at 8 weeks (patients were cultured at 4 and 8 weeks). We have entered 5 new patients at 600 mg and are continuing the study. Groups of 5 new patients will be entered at escalating doses. The dose for each group of 5 new patients will be raised by 150 mg until antiviral or toxic effects are seen. In addition, if no antiviral effect is seen after a patient re- ceives 8 weeks of therapy at a given dose, the dose will be escalated in the same manner. 202 THB234 Effects of 3‘ -Az1do*3'-deoxythym1d1ne (AZT) in Patients with Acquir- ed Immu une Deficiency Syndrome (AIDS) post- pneumocystls carinii pneumonia infection. DELIA F. CHIUTEN* **, P. MANSELL* **, L. McCRORV**, P. KUROWSKI**, M. HERNAN- DEZ; **, S. RODRIGUEZ* **. *U.T.S.C.C. M.D. Anderson Hospital and Tumor Institute, Houston, Texas, **Inst1tute for Immunological Disorders, Houston, Texas. AZT has been shown to limit multiplication of HIV through inhibition of reverse transcriptase. A clinical trial using AZT 200 mg every 4 hours p. 0. was 1nit1ated in 43 evaluable patlents with AIDS post- pneumocxstis car1n11 pneumonia (PCP) infection. Twelve concurrent opportunistic infections or tumor, 1. e. CMV ret1n1tis, Kaposi' s sarcoma, cryptospor1d1osis. candida esophagitis, mycobacter1um avium intracellulare and Burkitt' s lymphoma were present in some cases but d1d not require treatment while patients were receiving AZT. Med1an age was 33 years w1th med1an performance status of Karnofsky scale 90. All patients had 1 episode of PCP except 4 who had 2 ep1sodes of PCP prior to starting treatment. The main side-effect was anemia which occurred in 30% of the patients and 26% required blood transfusion. Other s1de-effects included nausea, headache, fatigue. anxiety, confusion and skin rash. Treatment was interrupted in 19 patients due to hematologic toxicity. opportunlstic infection, other infection and other medical problems. Twelve patients were treated for recurrent or possible recurrent PCP. Four patients refused further treatment due to intolerable gastrointestinal symptoms and fatigue. Clinical improvements were observed in the form of weight gain, decrease in abnormal liver function tests. increase 1n Hb and 1ncreased energy after taking AZT from 2 to lo weeks. All may have a role in the treatment of AIDS patients with PCP. 1112235 Improvement of Lymphoid Interstitial Pneumonitis in a Child Treated with Azidothmidine STEPHEN C. EPPES*, C.M. WILFERT*, K.J. WEINHOLD*, M.A. MAHA**, and S.N. LEHRMAN**, *Duke Univ. Med. Center, Durham, NC, **Burroughs-Wellcome, Research Triangle Park, NC A seven year old girl with ALL in prolonged remission developed generalized lymphadenopathy, Strep. pneumoniae septicemia, and bilateral pulmonary infil- trates three years after she had received blood products from 23 donors. Anti- body to HIV was present by ELISA and Western blot. She had hypergammaglobulin- emia, cutaneous energy, markedly low Th/T8 ratio and low total T4 number. IgG antibody to EBV capsid antigen was extremely high (124096) as was EBV early antigen (1:512). Her chest x—ray showed diffuse fine nodular opacities through- out both lungs and bilateral hilar adenopathy. Pulmonary function testing showed marked restrictive changes, however, blood gases were within normal limits. Open lung biopsy demonstrated severe chronic inflammation, mainly lymphocytes, in the perivascular, peribronchial, and interstitial regions and lymphoid follicles with germinal centers. No pathogens were demonstrated by routine or special stains. The child received 7 1/2 weeks of azidothymidine in— travenously; at no point did she receive other antiviral or immunomodulator therapy.Physica1 examination, chest x—ray and pulmonary function tests all showed marked improvement in her lung disease. Her lymphadenopathy and spleno- megaly also improved during 1V therapy. Blood and CSF cultures for HIV, both initially positive, showed distinctly less RT activity during IV AZT; immuno— logic parameters did not change significantly during the initial study period. There were no reductions in the EEV titers. The patient was continued on oral azidothymidine. THP236 Phase I study of the use of Lymphoblastoid interferon HuIFNd(Ly) and Difluormethyl- ornithine (DFMO) in the treatment of Acquired Immune Deficiency Syndrome (AIDS) related Kaposi's sarcoma. ADAN RIOS, J. REUBEN, G. BREWTON, AND P.W.A. MANSELL, Univ. of Texas System Cancer Center/Institute for Immunological Disorders. HuIFN¢(Ly) is active against AIDS-related Kaposi's sarcoma. (JCO, 1985:506). DFMO augments the in vitro antitumor activity of interferon. In addition, DFMO may be protective against the development of Pneumocystis carinii pneumonitis. We therefore are conducting a phase I study aimed at defining the maximum tolerated dose (MTD) of the combination of HuIFNaflLy) and DEMO in patients with AIDS-related K.S. The treatment plansconsists of the administration of HuIFNalLy) at a dose of 20x10 units/m intramuscularly (1M) daily x 30 days followed by the administra— tion of HuIFN¢(Ly) and DFMO in combination. The dose of HuIFNK (Lg) remains the same and DFMO was initiated at a dose of 6 grams /m by continuous infusion every day x 60 days. Nine patients with AIDS-KS have been treated and major toxici- ties have been thrombocytopenia and proteinuria. one patient has had a partial remission. It is anticipated that 20x10 units IM daily x 21 days every 28 days (8 days of rest period) with daily conti uous intravenous administration of DFMO at a dose of 3 grams/m will be the MTD for this combination. Phase II studies will then be conducted to determine the therapeutic efficacy of this combination in the treatment of AIDS-related K.S. THURSDAY, JUNE 4 THB237 Treatment of cytomegalovirus pneumonitis with foscarnet (trisodium phosphonoformate) in patients with AIDS MICHAEL G. ANDERSON*, C. FARTHING**, M.E. ELLIST, B.G. GAZZARD**, "St Stephens andlrlestminster Hospitals London UK;TMonsall Hospital, Manchester UK; andnhstra Clinical Research Unit, Edinburgh UK. Cytomegalovirus (CMV) is a frequent opportunistic infection in patients with AIDS and is associated with both high morbidity and mortality. CMV pneumonia has proved particularly difficult to treat with other experimental agents including 9—(1—3-Dihydroxy-2-propoxymethyl) guanine (DHPG). Foscarnet (trisodium phosphonoformate) has shown probable benefits when used for serious CMV infections in other immunosuppressed patients and we therefore undertook an initial study of this agent in AIDS patients with CMV pneumonia. Eight patients were included. Diagnosis of CMV pneumonia was based on the typical clinical features together with viral culture and the detection of early antigen fluorescent foci (DEAFF) with monoclonal antibodies in bronchoalveolar lavage specimens obtained prior to treatment. Following an initial bolus of 20mg/kg, foscarnet was administered as a continuous intravenous infusibn via a peripheral vein for between 8 and 26 days. infusion aimed at keeping the plasma foscarnet level at lSOpg/ml. Four patients had co-existing pneumocystis carinii (PCP) which had been treated for at least 3 days without clinical improvement prior to foscarnet therapy. Therapy for PCP was continued in all patients. All 8 patients improved following treatment, and 7 left hospital. Side effects included minor thrombophlebitis, reversible rises in serum creatinine and reversible anaemia. These results suggest clinical benefit of foscarnet in CMV pneumonia and a controlled trial is being undertaken. If A . CHANAS The THR238 Foscarnet—treatment in HIV-infected homosexual men. Susanne Bergdahl MD,Gunnel Biberfeld MD,Inger Julander MD,Jan-Olof Lernestedt dent, Linda Morfeldt-Ménson MD,Birgitta Asjd MD,Clin.depts Inf. Dis. Immunol. and Virol.,Karolinska Institute,Stockholm,ASTRA Pharm., Sweden. Phosphonoformic acid (Foscarnet) is an antiviral agent with in vitro activity against some retroviruses including HIV, all human herpes Viruses and HEpatit B Virus. Foscarnet selectively inhibits DNA—polymerases and reverse transcrip- tases. April -85 - April -86 14 men aged 20-AZ with PGL or ARC and poSitive HIV- cultures were treated with continuous infusion of Foscarnet solution in perife- ral veins. Treatment period was 2-3 weeks with a dosage of 0.14—0.16 mg/kg/min. Pharmacokinetics and clinical effects were studied. Results: Side effects. In 4 pats treatment was discontinued due to nausea. Nausea, headache-ana-fatiqe were most frequent and correlated to Foscarnet plas— ma levels. AII pats had a slight to moderate rise in their Se-Krea. levels. All side effects were rapidly reversible. Clinical symptoms such as nights sweats, bowel disturbances, fever periods tem- Eafafiiy‘aiéaafiééred or improved in about 80 x. The placebo effect must however be regarded as high. Follow up period was 3 - 4 months. Viral isolations. HIV was isolated in 20/25 cultures taken 6 months - 2 days be- fofE'ffeatméfiE_5nd in 10/39 cultures from the last day of treatment - 4 months after. I and I cells and immunoglobulins remained unchanged. Lymphocyte stimulation tesgs showed no significant changes. Conclusions: In view of Foscarnets broad antiviral spectrum, the encouraging clinical and Virological results of this study and the reversibility of Side- effects, further and controlled studies are important. Intermittent administra— tion of Foscarnet for longer periods but With lower doses may be one way. In Vivo antiviral effect against HIV remains to be proven for Foscarnet as well as for other antiviral drugs against HIV. Immunological and clinical tu THEzag seropoSitive patients. JgAu-HARLfi ANDPIEQ. PHILIPPE EVEN, ALAIN VENET, JEAN'MARf TOURANI, NARC STERN, WILLIAM LOWENSTEIN, et al.. Laennec HIV study group, Paris, France Cyclosnarin 7.5 my/Ag dolly given to :5 HIV seropositive non AIDS patients. Their characteristics were: mean age: 36 years lrange 20-55}, sex: males 3!, females 6. stages I1 (Tl cells/ul > 300, < 5001: 15, stages III lIl/ul (100): 10. 8 were asymptomatic, It had persistant generalized lymphadenopathies and J had constitutional symptoms The drug was given fur 3 5 months with the hypothesis that it could inhibit DCL HIV replication and the potential auto-immune component of HIV disease. A sustained and significant increase over 600 T4/ul occurred in I stages II and 1 stage III. A transient T4 cell peak was only observed in the other patients. TB cells/ul which were > 900 in 16 cases sharply decreased in ll patients and lymphadenopathies disappeared in 14/16. After cyclospurin withdrawal (4 and TB cells as well as Iymphadenapathies returned to preetreatment status within 2 months. The evolution of treated patients was compared to that u; a matched control group of 56 subjects. After a mean followeup u! 71 months, D/lé control and 3/10 treated stage; III evolved towards AIDS (2 oesophageal candidiasis, l reversible Kap05i's sarcoma) ; the figures were 4/42 and 0/15 for stages II. Cyclusparin side effect: lhypertensiun, creatinine increase and anaemia) were moderate and reversible. Inese results might stimulate biological research as well as clinical trials with Cyclospurin in selected groups of HIV seropositive subjects With the aim of delaying or preventing AIDS occurrence. Updated results Will be presented at the time of the Conference. response Cyclosporin in 25 HIV WJ 5 203 THP240 Immune Parameters of Patients with Acquired Immune Deficiency ' Syndrome (AIDS) /Kaposi‘s Sarcoma (KS) during Human Lymphoblastoid Interferon Treatment GEORGEANN &_ BARON, N.G. KLIMAS, M.R. ASHMAN, M.A. FISCHL, and ILA. FLETCHER, Univ. 3 Miami—$37601 of Medicine, Miami, FL, USA. Immune parameters were assessed for 35 patients with AIDS/KS before and longitudinally during treatment with human lymphoblastoid inte feron (IFN) (wellferon). IFN was given intramuscularly at a dose of 20mg/m daily for a wears, and patients without progressive disease contimed receiving interferon 3 times per week. Immunologic parameters assessed included mnonuclear cell surface market analysis; natural killer cell activity (SCYT) determined on an effector cell (0316+):target cell (K562) ratio of 1:1; proliferative responses to mitogens and antigen; and setup immnoglobulin levels. Won enrollment to therapy protocol, mtients had significantly decreased leukocytes, where of lymphocytes, tCD4+ cells; increased %CD8+ cells, %CD16+ cells and %CD14+ cells; decreased %CYT; decreased proliferation to mitogen and antigen stimulation; increased 196 and IgA compared to normal values. After 12 weeks of therapy, the patients remaining on protocol showed significant decrease in leukocyte count, in lymphocyte count, and in proliferative responses to phytohemagglutinin. 'Ihere was a significant increase in %CD4+ cells and increase in %CYT to 1662 cell line (p=.05 repeated measures analysis of variance). A second group of 22 AIDS patients with more extenfive KS received vinblastine administered intravenously at a dose of Smg/m every 2 weeks concurrently with IFN therapy. 'ihese patients did not show increase in %(D4+ cells or increase in %OI’I' after 12 weeks on therapy. These data suggest some degree of immunomodulation in these patients as a result of E vivo INF therapy which was not seen in patients with more extensive disease who reCived INF plus chenotherapy. Clinical 38d Imunologic Improvement in AIDS/ARC Patients Treated with IMREG -1, an Immunosupportive Agent THBZ41 A. ARTHUR GOTTLIEB, M.S. Gottlieb, C.H. Kern. Imreg, Inc. and Tulane Medical School,®New Orleans, LA and Cambridge, MA, USA. IMREG -1, a potent immunosupportive agent, isolated from normal human leuko— cytes by a series of HPLC separations, contains an active small peptide whose composition indicates that it may be®an important link between the neuro— endocrine and immune systems. IMREG -l augments delayed hypersensitivity (DTH) to recall antigens, and enhances the production of MIF, LIF and IL—2 by stimu— lated T4+ helper cells. a 50 patients with AIDS/ARC have been repeatedly treated with IMREG -1 in protocols lasting several months. Such treatment results in return of DH! in anergic patients, which is associated with enhanced mitogen induced prolifer— ative responses and lL-2 production. Such responses have been noted in over 60% of patients, and are associated with sustained stabilization of hematocrit, platelet and total lymphocyte counts. T4+ helper cell numbers increased or did not fall in 23 of 48 patients who were followed for three months. Weight gain, clearing of refractory oral candida and a decline in sergm hyperglobulinemia and uric acid levels were noted in some patients. IMREG —1 has a peak action at 7 to 10 days. The most beneficial esults were observed in patients having a minimum residual of 100 T4+ cells/mm . TBere has been no observable toxicity following prolonged adwinistration of IMREG —l for up to three years. The ability of IMREG —1 to reconstitute the ability of AIDS/ARC patients to mount antigen—specific immune responses is a fundamental indication of the effect of this agent on HIV-induced immunodeficiency. These important effects on the immune systsm coupled with the beneficial clinical effects observed suggest that TMREG —1 appears to be useful in ameliorating the immunodeficiency seen in AIDS/ARC patients. THPZ‘Z Variable Serologlc Status in Children with Hypogammaglobullnemia (HG) ' and Transfusion (TX) Induced HIV Disease NLC LUBAN*, A. WILLIAMS”, 5. JOSEPHS”, V. CRISS', G. REAMAN‘, Children's Hospital National Medical Center, Jerome H. Holland Laboratory, American Red Cross, Washington, D.C. and Rockville, MD. As part of a prospective study of highly transfused infants and children, we have identified two children with EIA positive, Western blot (WB) confirmed HIV disease and subsequently identified HIV infected donors in both. Both children had profound HG at the time of receipt of the implicated tx and for a time subsequent to its receipt. They had received units of fresh frozen plasma (FFP) from different donors at 2 days of age for treatment of severe hyallne membrane disease and at 5 years of age during therapeutic plasmapheresis for immune thrombooytopenia, from which both recovered. Both patients remain ElA/WB positive; one has oxygen dependent bronchopulmonary dysplasia, is now normoglobulinemlc, with normal T4/TE ratio and has positive HIV cultures, now 2 1/2 years post receipt of the FFP. The other has biopsy proven lymphoid interstitial pneumonltls, has normal immunoglobulins but reversed Tit/T8 ratio. Two additional children were identified as recipients of blood from HIV infected donors but were EIA, RIP and WB negative repeatedly despite clinical presentation and symptoms of AIDS/ARC in both. One received washed packed red blood cells (PRBC) at 25 days of age and the other FFP at 3A days of age. Both were 26 week gestation premature infants who had multiple episodes of fungal d: bacterial sepsis, pneumocystis pneumonia, monoliasis and thrombocytopenia culminating in death at age 49 months and Ill months, respectively. One had normal lmmunoglobulins for age prior to receipt of the implicated unit. Both developed profound HG. One of the two was cultured for HIV and had positive reverse transcriptase activity on day 2l of culture. Autopsies on both were consistent with HIV disease. These data suggest that post-transfusion HIV infections result in variable serological manifestations and that EIA/WB tests alone may be inadequate diagnostic tools to document HIV disease in some children with HG. THURSDAY, JUNE 4 THR243 EVALUATION OF A SYNTHETIC PEPTIDE BASED HIV-EIA. Barbara Hosein. William Ying, Louis Baker, William R. Oleszko, Beverley Lightbourne, and Celso Bianco. The New York Blood Center, NY, NY. Our center has evaluated a synthetic peptide based ELISA assay for antibody to HIV developed by UBI-Olympus. The solid-phase antigenic adsorbent employs polypeptides synthesized chemically with sequences corresponding to highly antigenic segments of both envelope (gp41) (PNAS 83, 6159-63, 1986) and core (P24) proteins of HIV. The initial reactive rate in 2000 random donors who designated their units for transfusion is 0.85% and the repeat reactive rate is 0.252. of the repeat reactive samples, 401 are positive by Western Blot (WB) analysis. The specificity if this assay is 99.85%. Samples (n=505) found to be repeat reactive in other licensed HIV antibody assays at our center were retested with the synthetic peptide-based assay. All of the 419 WB positive samples tested were reactive, whereas only 2 of the 86 WE negative samples were reactive. Sequential samples (n=90) collected at short intervals from 13 individuals who seroconverted during the period were tested by this assay, by those of six other manufacturers, and by WB. The peptide based assay detected HIV anti— bodies earlier than did all other ELISAs in 2 individuals and earlier than or equal to all other ELISAs in ten other individuals. It detected HIV antibody two to five weeks prior to detection by NE in 5 of the 13 individuals. The synthetic peptide based assay has the potential to eliminate non-specificity associated with host cell antigens. Its detection of antibody in all WB positive samples studied and its high sensitivity in seroconversion samples suggest that all individuals exposed to HIV make antibodies against a restricted set of amino acid sequences of HIV. THRZ44 R HADHOK JA GRACIE E FOLLETT A BURNETT GDO LOWE CD FORBES GLASGOW ROYAL INF UNI DEPT MED GLASGOW SCOTLAND IMPAIRED CELL IEDIATED IMMUNITY (CII)IN HAEHOPILIA We and subsequently others have shown that lyophilised factor concentrates are in immunosupressive in vitro.The aim of this study was to determine if haemophiliacs treated with factor concentrate show immunosupression.The CMI response was evaluated in 29 haemophiliacs by means of the DNCB skin test.All patients had a response below the lower limit of the normal range.No differe nce was seen in the skin response between pts positive and negative for HIV In the whole grp.&in seronegative pts.(N=17)there was an inverse correlation between clotting factor concentrate exposure dthe skin response .In HIV posi tive pts no such association was apparent. The T—4 count showed a correlation (r=.49)with the skin response in HIV ne gative patients but not in HIV positive pts.In positive pts.a correlation was seen with T—8 cnt.(r=.45). This study shows that clotting factor concentrate impairs the CMI response to a new antigen in the absence of HIV infection .Future studies may show a lower response in positive patients as HIV immunosupression may take years to devlop. THP245 Characterization of HTLV—III (HIV) and HTLV—I Antibody Reactive ' Sera by Specific Western Blot Assays. STEVE S. ALEXANDER, A.J. BODNER, A.J. CORRIGAN, T. CLEMENT AND W.R. FREDERICK*, Biotech Research Laboratories, Inc., Rockville, MD and *Howard University Cancer Center, Washington, D.C. Western Blot assays have been developed to identify the antibody specificity of HTLV—III (HIV) and HTLV-I ELISA reactive samples. Most strongly reactive HTLV-III samples contain antibodies to all major viral proteins: ENV (gp41/160), GAG (p17, pZA/SS) and POL (p31, p51/66). HTLV-I reactivity is primarily directed against the major gag proteins p19, p24 and their intermediates. Both Western Blot assays were carried out on a large group of predominantly black IV drug users. More than half of the positive sera were reactive in both assays. The majority of these samples contained antibodies to the major viral proteins of both viruses indicating co—reactivity rather than cross reactivity. Previous analysis of another group of HIV positive on HTLV-I and a HTLV-I group on HIV demonstrated minimal cross reactivity. Concomitant infection with HTLV—I and HIV has been reported (Harper et a1. (1986) New Eng. J. Med. 315, 1073—1078). Our results indicate a significantly high frequency of dual exposure/infection among this particular at—risk population. 204 THBZ46 Assessment of the Demographic and Motivational Characteristics of HIV Seropositive Blood Donors ALAN E. ELLLIAMS: S.KLEINMAN**, H. M. POPOVSKY****, __ , LAHBERSON***, K. WILLIAMS*, R.DODD*, et al. *Jerome H. Holland Laboratory, American Red Cross, Rockville, MD. **American Red Cross Los Angeles-Orange Counties, ***Syracuse, N.Y., and ****Northeast Blood Services Regions. Seventy five male and 14 female blood donors found to be conflrmably HIV seropositive during routine blood donor screening, together with age and sex matched controls, have been enrolled into a five year multi-center prospective study. For 59 males (78%), the primary hierarchical risk for HIV infection was sexual contact with other males; the mean number of partners was 25.5 (range 1- 250). Of 14 males whose primary risk was parenteral, 8 had a history of IV drug use, and 6 had a history of prior transfusion. No established AIDS risk factors were found during Interviews with 8 seropositive males. 0f the 14 HIV+ females enrolled, the primary hierarchical risk of HIV exposure was sexual contact with bisexual or IV drug abusing males (50%). Parenteral exposure via drug use or transfusion was the primary risk for 4 seropositive females. No AIDS risk factors could be determined for 5 females. Prior STDs were reported in 52% of index donors vs. 9% of controls. Forty five percent of index donors suspected that they were in an AIDS risk group at the time of donation. These individuals reported the following motivations for blood donation despite self-deferral measures: peer pressure to proceed with donation (29%), desire to learn HIV status (29%), self-denial of risk status, or impression that their blood was of particular value (61%) appeal for self-deferral not taken seriously (6%). Additional interview data indicated that 65% of donations from subjects with self-recognized AIDS risk would not have been excluded by a confidential designation that their blood donation should not be used for transfusion. THP247 Comparative HIV Antibody Testing in Blood Donors ' CHERYL A. MCMAHON, N.L. DOCK, H.V. LAMBERSON, American Red Cross Blood Services;'Syracu'Ee""NY' . We have screened 164,775 blood donations for ant1body to HIV by two ELISA'S: 120,229 samples were tested b Abbott EIA from Mar. '85 - June '86; 44,546 samples were screened by the Du ont ELISA from July ‘86 - Dec. '86. The Abbott initial react1ve rate (IR) ranged from 0.2 - 5.8% per week; the repeat reactive rate (RR) was .44% (range: 0 - 1.5%). Abbott Western blots (NB) on 531 RR samples were: 488 (.41%) negative 12 (.01%) positive and 31 (.031) atypical. he DuPont IR rate was . - 1.1%; the RR rate was .57X (ran e .2 -.8%). NB performed at Biotech Research Labs (BTRL) on 255 repeat reac Ive samples were: 114 (.261) negatIve, 3 (.007%) positive and 138 (.311) aty Ical. Samples found to be ME positive or at pical were submitted to both la 5 for compar1son. The same 15 samples were Identified as HB(+) by both labs but there was a wide variation in the reporting of atypical NB. 0f the 31 samples originall regorted as Abbott NB atypical, 27 (8 S) were DuPont ELISA (-) BTRL NB (- . ubsequent samples on [31 have remained DuPont ELISA(-) BTRL HB(-) 4 others remain B RL NB atypical. 0f the 138 BTRL HB atyEical samples, 28 (93%) were Abbott HB(-) and 10 (7%) were atypical. leven of the Abbott (-) DuPont (+) BTRL HB aty ical donors have returned for subsequent donations. Seven of 11 remain BTR NB atypical, Abbott ElA(-) NB(-); 2/11 are now negative on all assays. Two remaining Abbott EIA(-) DuPont ELISA(+) donors with p24 on both B's returned wi hin 2 months, were reactive on both screening assays and were iully positive on both NB. The or1ginal samples from these donors are reactive on the recently licensed modification of the Abbott EIA. These results suggest that sensitivity and specificity of screening tests are evolving an that there is considerable variation in NB procedures. Ongoing comparative testing of blood donors is essential to assess assay performance and develop donor notification strategies. HIV Seroconversions after Heated Clotting Factor Concentrates in Hemophiliacs. THRZ48 GUGLIELMO MARIANI“, A. GHIRARDINI“ P. VERANI“ F. MANDELLI” G.B. ROSSI‘, P.M. MANNUCCI*** et. a1. ”Dept. Hematology, "La Sapienza” Univ. of Rome, Italy; *“Dept. Virology, Istituto Superiore Sanita, Rome, Italy; ***A. Bianchi Bonomi Hemophilia B Thrombosis Center, Univ. of Milano, Italy. In Italy, heated concentrates became the only source of hemophilia therapy since July 1985. Since then 63 anti—HIV seronegative hemophiliacs treated with heated concentrates were followed—up prospectively, focusing on seroconversions. Anti-HIV (documented by ELISA and WB) occurred in 6 patients without other risk factors for HIV infection. For 3, anti—HIV was first found in Sept., Oct. or Nov. 1985. Another patient seroconverted in Sept. 1986, but no sample was available after the last negative test (Nov. 1985). For these 4 cases we cannot exclude that seroconversions are due to nonheated concentrates. The remaining 2 patients seroconverted in July 1986. For both, a hemophilia A patient (treated only with a concentrate dry—heated for 72 hr at 68°C) and a hemophilia B patient (treated with both a steam-heated and a dry—heated concentrate for 72 hr at 68°C) the last seronegativities were found in March 1986, 7.0 and 7.5 months after commencing the use of heated concentrates or 3.5 and 4.0 months before the first seropositivity. In conclusion, two seroconversions occurred in previously seronegative patients treated exclusively with heated concentrates. Intensity and duration of concentrate exposure to heating were greater than those for dry—heated concentrates (60°C for 30 hr) that induced two reported seroconversions. i.e. THURSDAY, JUNE 4 THP249 Experience with a Competitive ELISA for HIV Antibody in Blood ' Donors in the USA JAMES F. KELLY, R.P. ELKINS, B.J. ROSENBERG, The Wellcome Research Laboratories, Research Triangle Park, NC USA Sara and plasma from 12150 blood donors at 4 different geographic locations were tested with a competitive ELISA for anti—HIV antibody (Wellcozyme, Wellcome Diagnostics; Dartford, England). Samples were tested in parallel at each site with a noncompetitive assay for HIV antibody. All samples initially reactive by either HIV ELISA were retested by Wellcome and examined by western blot. The wellcome ELISA results obtained by the 4 laboratories are given below: INITIAL REACTIVES REPEAT REACTIVES # Samples —— Laboratory Tested No . i No . Q A 3,137 6 0.19 2 0.06 5 3,018 7 0.23 l 0.03 C 3,001 6 0.20 1 0.03 D 2,994 1 0.03 0 0 MALS 12,150 20 0.16 4 0.03 Only 1 of the 65 initially reactive specimens was reactive on repeat test in both HIV assays. This sample was also reactive by western blot. THP.250 ABSTRACT NOT AVAILABLE AT TIME OF PRINTING 205 FRIDAY, JUNE 5 Epidemiology—HIV-AIDS Cofactors F_1.1 U.S. Department of Defense HIV Testing Programs: An Overview. DONALD S. BURKE", J.F. BRUNDAGE*, R.R. REDFIELD”, P.W. KELLEY*, LR. HERBOLD , et s1., *Walter Reed Army Institute of Research, Washington, D.C., **0ffice of the Assistant Secretary of Defense (Health Affairs), Washington, D.C. In 1985 and 1986 the US Department of Defense instituted programs for routine HIV testing of the following populations: civilian applicants for military service, active duty personnel, National Guard, and Reserves. Separate programs are conducted by the Army, the Air Force, and the Navy and Marines. In all programs, sera are screened by ELISA, and repeatably positive specimens are tested by Western blot. Through December 1986 over 1.9 million persons have been tested. The mean prevalence rate of positive Western blots among civilian applicants for military service is 1.5 per 1000 and among active duty personnel it is 1.6 per 1000. Age, male gender, and black racial group are independent risk factors for seropositivity. The ratio of male:female prevalence rates is 2.5:1. A summary of prevalence data and of demographic factors associated with HIV seropositivity is presented. F.1_2 HLA Phenotypes are Possible Risk Factors for Development of AIDS. DL MANN*, C_Murray**, JJ Goedert*, WA Blattner*, M Robert- Guroff*,* National Cancer Institute, Bethesda, MD and Braton **Biotech, Inc, Rockville, MD To evaluate a possible immunogenetic role for developing AIDS, we HLA typed 226 white homosexual males, 91 who were HIV seronegative, 135 seropositive of whom 56 had AIDS (28—Kaposi's (KS), 28-opportunistic infections (01)or subsequently developed AIDS. The frequency of individual HLA antigens in the HIV negative population was similar to North American caucasians. HLA-001 was higher in frequency in all AIDS patients (77%) compared to HIV+ non-AIDS individuals (56%). HLA-DRI was higher in frequency in 01 patients (39%) compared to KS (25%) and HIV non-AIDS (16%) HLA-0R3 frequency was 36% in 01 patients, 14% in KS and 28% of the at risk group. HLA-0R7 was found in 29% of KS compared to 4% in GI (HIV+ non-AIDS, 19%). HLA-DRw53 was also higher in frequency in KS (60%) compared to OI (15%) (HIV+ non—AIDS, 44%). In 106 HIV+ individuals enrolled in the study in 1982, 44%:14% DR1 individuals developed AIDS during this 4 year period while AIDS occurred in only 19%:5% DRI neg. individuals. Total numbers of CD4+, CDB+ cells were virtually identical in 1982. These data demonstrate that the HLA— DR phenotype may be associated with an increased risk for developing AIDS after exposure to HIV and that certain phenotypes may be associated with KS or 01. The mechanism whereby this risk is conferred is not demonstrable. However since HLA-D region molecules are recognition elements in the immune response, specific molecules may tend to promote or protect in development of AIDS. [:13 Familial Tendency to Serious Sequelae of HIV Infection. ” , RR. KRAUSE , M.M. LEDERMAN , P.H. LEVINE , M.E. WSTER’, G.C. WHITE , e1 . Case Western Reserve Univ., Cleveland OH, Univ. Mass, Worcester MA, enn State Univ., Hershey PA, 'H'Univ. N. Carolina, Chapel Hill NC. Cofactors for the development of serious complications of HIV infection are not well recognized. To ascertain if genetic factors might contribute to the outcome of HIV infection, we examined 34 sibships wherein at least two siblings with classic hemophilia had serologic and/or clinical evidence of HIV infection. HIV-infected subjects were classified as having a) no symptom (with or without generalized lymph node enlargement) b) AIDS related complex (ARC), c) AIDS, d) thrombocytopenia (T) (<150,000 platelets/uL on at least 2 occasions) e) leukopenia (L) (<3,000 WBC/uL) or combinations of clinical and hematologic manifestations. As of December 1986, 31 of 52 patients for whom complete information was available were asymptomatic. 5 of 52 had developed ARC. 5 of 52 had developed AIDS. 8 of 68 had L. 13 of 68 had T. Siblings of patients with AIDS or ARC had a 75% chance of having AIDS, ARC. L or T as opposed to an 11% risk of these complications among sibs of asymptomatic hemophiliacs (p - 0.003, Fisher Exact). The risk of AIDS or ARC among sibs of patients with AIDS or ARC was 33% vs. a 10% risk among sibs of patients without AIDS or ARC (p - 0.22) Siblings of patients with T or L had a 44% chance of also having T or L as opposed to a 12% chance among sibs of patients without T or L. This concordance was almost significant (p - 0.06). These data suggest that there is a familial tendency to certain serious complications of HIV infection or that other factors common to sibs may contribute to the outcome of HIV infection. These observations warrant longitudinal follow-up of sib pairs and expansion of the study to identify factors that affect the outcome of HIV infection. F.1.4 Age and Cumulative Incidence of AIDS among Seropositive Homosexual Men in High Incidence Areas of San Francisco. JAMES A. WILEY*, GEORGE W. RUTHERFORD**, ANDREW R. MOSS***, WARREN WINKELSTEIN, JR.*, *U.C. Berkeley, CA, **San Francisco Department of Health, San Francisco, CA, ***University of London, England. From a probability sample of homosexual men living in 19 census tracts of San Francisco where AIDS was most prevalent, we estimated the age-specific prevalence of infection by HIV. By March 31, 1986, 805 cases of AIDS were diagnosed among an estimated 8,346 seropositive men, aged 25—54, in this area, yielding a rate of 96.5 cases per 1,000 seropositives (95% confidence interval, 86.6 to 108.8 per 1,000). Cumulative incidence was more than twice as high among older (aged 35-54) than among younger (aged 25-34) men (144.5 vs. 67.8 per 1,000, p<.001). To investigate whether or not the association between age and cumulative incidence was due to earlier infection of older men, we examined the relation between current age and serostatus in 1978 in a sample of 394 homosexual men from the San Francisco City Clinic Cohort. There was no relation between age and early infection in this sample. Moreover, age was inversely related to the rate of seroconversion from 1978 to 1984 (chi-square test for trend - 11.4, ldf, p(.0001). We conclude that the higher cumulative incidence of AIDS among older men cannot be explained by the hypothesis that older infected men seroconverted earlier than younger infected men. Other hypotheses, including the possible effects of age—related co—factors of disease progression and of biological aging, need to be examined. F 1 5 Hepatitis B virus coinfection in homosexual men seropositive for ' ' human immunodeficiency virus antibody DENNIS OSHOND, R.CH.AISSON, P.3EASLEY, P.3ACCHETTI, A.MOSS. UCSF and SF General Hospital, San Francisco, California, USA Among subjects positive for anti-HIV in a cohort of initially healthy homo- sexual men under prospective study for risk of AIDS, we examined the associa- tion of HBsAg with impairment of cellular immunity and progression to AIDS. At baseline 62% (292/469) were seropositive for anti-HIV and 871 (410/469) had one or more serological markers for HBV. Of HBV seropositives, 101 (39/410) were seropositive for HBsAg and of HBsAg seropositives 742 (29/39) were also posi- tive for anti—HIV. Among the 29 HBsAg carriers who are anti-HIV positive, 1 developed AIDS (3%) over 2 years of followup compared to 40 of 258 (16%) anti- HIV positives who are not HBsAg carriers (OR-0.19,p-0.057). Comparing anti-HIV positive subjects with any HBV antibody marker with subjects with no HBV mar— ket, 38 of 240 (16%) HBV Ab positives developed AIDS versus 2 of 15 (13%) with— out HBV markers (p-0.78). Among anti—HIV seropositivea, HBsAg carriers were significantly less likely at baseline to have an l-I/S ratio below 0.6 (OR-0.29, p=0.025). At l—year followup HBsAg carriers were again less likely to have an H/S ratio below 0.6 (0R-0.3l,p-0.08). These observations suggest coinfection with HBsAg may be associated with reduced pathology of HIV infection. Supported by a grant from the Universitywide Task Force on AIDS. F 1 6 Association of Anogenital Ulcer Disease with Human Immunodeficiency Virus ' ' Infection in Homosexual Men a gunman ngwpsflzpp‘vz, R. L. ASHLEYZ. A. M. ROMPALOZ, w. s. STAMMZ, R. W. WOOD ' and L. COREYZ, Seattle-King Cgumy Department of Public Health1 and University of Washington School of Medicine , Seattle, Washington, USA To test the hypothesis that genital or anoreclal ulcer disease predisposes to acquisition of HIV, 2 groups of homosexual men (HM) were studied. Type-specific herpes simplex virus (HSV) antibody (Ab) was measured by Western blot (W13); HIV Ab was analyzed by ELISA (Genetic Systems) and WB; the hemagglutination treponemal test for syphilis (HATTS) was performed. Of 176 HM with acute proclitis or enteritis, all of whom participated in receptive anal intercourse, 103 (59%) had HIV Ab and 145/167 (87%) had Ab to HSV-1 and/or HSV-2. HSV-2 Ab was present in 77% of subjects with HIV Ab, compared with 37% of those without HIV Ab (P<0.0001). By logistic regression, control- ling for numbers of sex partners in the preceding 1 mo, 6 mo and lifetime and years of sexual activity, the following were significantly associated with HIV Ab: HSV-2 Ab (odds ratio [OR]) 4.0. P-0.0005), past history of genital or anoreclal herpes (OR 2.7, P=0.018)), past oral herpes (OR 4.0, P=0.02), and past syphilis (OR 4.8, P-0.0007). In a separate group of 109 HM seeking AIDS counseling, HSV WB was performed in 99; HSV-2 Ab was present in 31 (74%) of 42 HIV-positive and 15 (26%) of 57 HIV- negative subjects (P<0.0001). HATTS was reactive in 9 (18%) of 49 HIV-positive and 3 (5%) of 60 HIV-negative subjects (P-0.047). These associations also persisted when controlling for number of sex partners. Past HSV infections and syphilis are significant risk factors for HIV infection in HM, perhaps because they cause mucocutaneous ulcers that facilitate HIV acquisition. FRIDAY,JUNE5 Virology—Diagnostics F 2 1 Correlation between Antibody Response to HIV Antigens, Neutralizing ' ' Antibody Titers and Clinical Status. FRANCOISE BARRE-SINOUSSI*, F. REY*. S. GHARAKHANIAN**, F. 0LLIVIER-HENRY*, W. RUZENBIUM“ and J.C. CHERMANN*, Institut Pasteur, Viral Oncology Unit, Paris, France, **Pitie-Salpetriere Hospital, Paris, France. The antigen specific antibody response in 159 sera from HIV seropositive. patients has been analysed by Western blot. The samples were including two sequentiel sera from two groups of individuals. Group 1 was corresponding to individuals with no evolution in the disease (5 asymptomatic carriers, 28 lym- phadenopathy and 4 ARC patients). Group 2 was corresponding to patients who developed AIDS (3 asymptomatic carriers, 15 lymphadenopathy and 6 ARC patients) In the first group, the mean time between the 2 serum samples was about 30 months whereas in the second group, the mean was approximatively 17 months and the second serum sample was at the time of the disease. A lower antibody res- ponse to viral antigens was observed mainly in group 2. Neutralizing antibody activity of 18 sera from group 1 and of 22 sera from group 2 was also studied. In group 1, 4 out of 9 patients presenting high antigen antibody response have increasing neutralizing titers with no changes in Western Blot patterns. In group 2, 9 out of 11 patients have constant or decreased neutralizing titers and antibody response. The decrease of neutralizing antibody titers seems to correlate with the lower antibody response observed in the second serum sample. The lower reactivity of this sample by Western Blot was concerning mainly the one to HIV core antigens. Such prospective studies might be important for pre- dictive status of the disease outcome. F 2 2 Virologic Studies in the Diagnosis of Pediatric AIDS ' ' WADE EL PARKS'. E.S. PARKS‘, C. HUTTO‘. G.B. SCOTT‘. J.E ALLAIN". ‘Department 0 ediatrics. University of Miami School of Medicine, Miami. FL.. "Abbott Laboratories, North Chicago. IL. The diagnosis of AIDS virus infection in infants during the first 12 months postpartum is complicated by the presence of maternal anti-viral antibody. Virus isolation in infants who present with or subsequently develop AIDS-associated clinical disease was positive in 78/94 (831) cases on the first isolation attempt. A11 virus positive infants were seropositive in immunoassays with virion p24 and bacterially synthesized components of gphl protein. Two approaches have been utilized to provide surrogate tests for virus isolation which is currently the definitive laboratory measure of infection. First. decline of maternal antibody was evaluated in 6 infants who were born to seropositive mothers but were themselves not infected as evidenced by normal clinical. immunologic and virologic findings in a follow-up averaging 36 months (range 26-50 monthsL Both p24 antibody and gphlE antibody declined to baseline by 12 months from high levels immediately post-partum. Conversely. by 12 months of age. all infected infants had easily detected antiviral antibodies. The second approach was to utilize a p24 antigen detection ELISA on serum and plasma from virus positive infants. Antigen positive plasma from 18 infants was virus positive in 17 instances: 15 patients were antigen negative but virus positive; all antigen negative virus positive patients had high levels of anti-pzh antibody. No antigen negative. antibody negative. virus—positive infants have been detected in over 125 infants that have been tested. Thus. it is possible to utilize a combination of p24 antigen detection and anti-p24 antibody determination in pediatric patients to achieve objective laboratory diagnosis of AIDS virus infection. I: 2 3 Identification of HIV Sequence in DNA Extracted Directly from Peripheral ' ' Blood Lymphocytes apd Bone Mar ow Using lg Vi ro DNA Ampli ication. JOHN J SNINSK , . KWOK , . MACK , G. EHRL CH , . ULLRICH , B. POlESZ , et al. CetuaCorporation, Emeryviile, CA. SUNY Upstate Medical Center, Syracuse, NY, University of California, San Francisco, CA. While serological tests have significant sensitivity and specificity for the identification of antibodies against HIV, they do not provide direct identification of the virus. The identification of virus generally requires co-cultivation of patient specimen with permissive cells, followed by either assays for reverse transcriptase activity, immunoiiuorescence using antibodies to the structural components of the virus, or Southern blot analysis. Because the number of infected cells is generally low and due to transcriptional domancy, these procedures are often inadequate for detection of virus. We have used the polymerase chain reaction (PCR) and oligomer restriction (OR) procedures to amplify and detect HIV viral sequences. These procedures are both sensitive and specific for HIV and can detect as few as 25 genome copies in 200,000 cells. Previously, we reported the successful identification of HIV sequences in cell lines established from AIDS and ARC patients. These included cell lines that were devoid of reverse transcriptase activity and/or negative by Southern blot analysis. We report here that PCR-OR can identify HIV viral sequences in DNA extracted from mononuclear cells of fresh blood and bone marrow, thereby eliminating the lengthy process required for cell culturing. Notably, these procedures have also made possible the identification of HIV viral sequences in asymptomatic, seropositive individuals as well as in seronegative, culture positive individuals who are at risk for AIDS. Optimization of the amplification procedure and overall sensitivity and specificity of the assay will be presented. 207 F 2 4 Double Hl\4-1 and HIV-2 seropositivlty in1four.pafients iq Paris. ' ' M.HARZ|C, Fran oise BRUN-VEZINET. A.G.SA|MOT F.COURTOIS2 Y.DOMART,3 S.WAlN—OBSON et al, Hopital Claude Bernard1. Bichat? Louis Mourier? Institul: Pasteur, Paris. France. The presence of antibodies to both HIV-1 and HIV—2 has already been described in sera from AIDS patients In Central African Republic and Ivory Coast. This double seropositivity is probably not a recombinant event but rather a double infection. We report here four cases of double HlV—i/HlV—Z seroposltivlty In patients (pts) who have been living in France for several years. Two originated from West Africa: pt1 (21 years) born in Ivory Coast has been living in France since 1984, he is a heterosexual single male with numerous partners, one beeing an intravenous drug abuser. Pt2 is a 37 years old female from Ghana, having had 2 Ghanaian partners and living in France since 1978. Pta (37 years) and 4 (33 years) are whlte homo— sexual males, pt3 having multiple West African partners since 1980. All the 4 pts presented with AIDS-related complex (group III, subgroup A) diagnosed in 1986. In the 4 pts lgG antibodies to HIV-1 and HIV-2 were detected by Elisa and Western blot (Diagnostics Pasteur). Double HIV—1/HIV-2 seropositivity was demons- trated on the presence of antibodies to HIV—1 (gplGO-gp110 and gp41) and HIV-2 (gplso-gp105 and gp 41) envelope glycoprotelns. ln pts 2, 3 and 4 immunoblot analysis showed variable reactivities against the gag and pol gene products of HIV-1 and HIV-2. A similar banding pattern for HIV-1 and HIV—2 was observed in sera collected in 1985 for ma and in 1984 for pt4. Retrovlral isolates were performed from the peripheral blood lymphocytes of the 4 pts. Isolates were caracterized by Southern blot analysis. Neutralizing antibodies to HIV-1 and HIV—2 were evaluated. These data showed that HIV-2 infection was present in the french gay community in 1984. To diagnose HlV-1/HlV-2 double infection HIV—1 and/or HIV-2 Elisa posi- tive sera should be checked by HIV-1 in! HIV—2 Western blot. Evaluation of the pathogenicity and the extent of this double HlV-1/HlV—2 infection is needed. F 2 5 Efficacy of five HIV enzyme immunoassays (EIA) in detecting ' ' ‘ antibody to HTLV-IV. * ‘. ** F.A. Denis , G. Leonard , H. Hounier , A. Sangare , Gg Gershy-Damet , F. Barln . at al., C.H.U. Dupuytren, Limoges, France, Institut Pasteur, Abidjan, Cote d'Ivolre, CHRU Bratonneau, Tours, France. Recent seroepidamiological studies show that STLV-III related human retroviruses (HTLV-IV, LAV-II) are widely present in West-Africa. Moreover HTLV—IV- or LAV-II- seroposltlve subjects have been found occasionally in Europe. Since no type specific ELISA is yet available we have compared the performance of 5 HIV commercial 31A: in detecting cross-reactive antibodies to HTLV—IV. The assays evaluated were from Abbott, Organon, Pasteur (two wells) and Wellcome. A fifth EIA, from Abbott, was also evaluated. This EIA is a competitive immunoassay employing as antigen recombinant DNA— produced HIV proteins (ENVACORE ). In this assay every sample is tested for the presence of antibody to either core proteins or envelope proteins. Preliminary results on 26 sera from healthy West-African residents positive for antibody to HTLV-IV (serotype specificity assessed by western—blot and/or radioimmunoprsclpitatlon) indicate that the HIV test kits are not equally efficient in detecting HTLV—IV antibody positive sera. The Wallcome test was the less sensitive (42 1 positivity) whereas the ENVACORER kit was the more sensitive (96 1 positivity). The Organon, Pasteur, and Abbot first generation BIA kits detected 73 X, 81 X, and 92 X of HTLV—1V antibody positive sera, respectively. Futhermore, approximately 50 X of people exposed to HTLV-IV develop antibodies that cross-react with a recombinant DNA derived HIV antigen from the 35! region containing all amino acids of gp Al as well as a portion of gp 120. These results indicate that the 53! gene products of HIV and HTLV-IV are conserved to the degree that they are serologically cross-reactive. Results on larger series will be presented. This data must be considered when regarding African seroepidemiological studies as well as screening of blood donors. F 2 5 Diagnosis of HIV Infectlon: Utility of Radioinmunoassays for ' ' the Major Internal Antigen (p24) and Transmembrane Envelope Glycoprotein (gp4l) of Human T-Cell Lymphotroplc Virus, Type III (HTLV III). SUSHIL G. DEVARE. J. M. CASEY, D. A. PAUL. M. D. LEUTHER, J. S. HELLER, G. . DA N. et a ., Abbott Laboratories. North Chicago, IL. The radiolmmunologic techniques have provided invaluable avenues in epidemiologic studies of retroviruses. In the present studies we have developed specific and sensitive immunoassays for the major internal antigen (p24) and the transmembrane envelope glycoprotein (9p41) of HTLV III purified from the density gradient banded virus preparations. In an attempt to evaluate their utility in diagnosis, sera from patients with acquired immunodeficiency syndrome (AIDS), AIDS related complex (ARC), clinically asymptomatic as well as normal Individuals were tested for antibodies to p24 and gp41. High titered antibodies to gp4l could be readily detected in 100% of the sera from AIDS patients, whereas, only 70% of these patients exhibited antibodies to p24. These data, along with the analysis of sera obtained from sequential bleeds of patients throughout the course of infection and the disease, indicated that antibodies to gp41 persist, while the antibodies to p24 are either not detected or have much lower titers during late stages of infection. The sera from the individuals which lacked detectable levels of antibodies to p24 were subjected to an enzyme linked immunoassay which detects presence of HIV antigens (predominantly p24) in the body fluids. These analyses revealed that in a large number of cases. the lack of antibodies to p24 in the sera correlated with the presence of HIV antigen. Based on these observations, the antibodies to gp41 are the most consistent marker for evaluation of HTLV III exposure, whereas, antibody titers to p24 may indicate various stages of the disease. FRIDAY, JUNE 5 Clinical Management—Infections II F.3.1 Cross—Allergy to Sulfonamides/Sulfones (Sulfa), folic antagonists in AIDS and ILEANA MEDINA, FEIGEL D, WOFSY C. UCSF School of Medicine, San Francisco General Hospital, San Francisco, CA, USA. Thirty AIDS patients who showed sulfa allergy following Pneumocystis carinii pneumonia (PCP) treatment were rechallenged with another sulfa. 21 pts received Trimsthoprim—sulfamethoxazole (TS) for first episode PCP and developed a major allergy (9 rash, 10 fever, 5 9 NBC, 1 4 LFT's). When they received dapsone/TMP (DT) for the second PCP, 6/21 showed side effects (4 rash/fever, 1 yWBC, 1 Vplates) 7—10 d after the initial dose. Four of these 21 pts also received Pyrimethamine (Pyr) and Sulfadiazine (Sdz) for toxoplasmosis; 2 showed severe rash 2 and 6 wks later. Two of 21 also received Pyr-Sulfadoxine (Fansidar) for PC? prophylaxis; 1 developed a rash after 4 wks. Nine pts were allergic to DT for the let episode of PC? rash/fever, 1 V WBC 1‘V plates); all 9 received T5 for 2nd episode PCP w/o side effects; 3 received Pyr/Sdz (1 developed rash at 10 days; 2 had no side effects); another received Fansidar w/o incidents. Of the 21 pts with initial TS allergy 3 were rechallenged with TS during a subsequent episode of PCP; 2 pts who received >8 d of TS developed the same- side effect (rash/fever) 7 & 10 days after the initial dose. The 3rd received 4 d of TS IV w/o side effect; all finished 21 d of total therapy. There is no cross—allergy between T5 and DT; often no cross— allergy between different sulfonamides, sulfones, & folic antagonists. Rechallenge with the identical agent (TS) is often well tolerated and may be undertaken in selected circumstances. (7 F.3.2 Diminished Sulfa-Trimethoprim(ST) Toxicity in Blacks Treated for Pneumoozetis carinii Pneumonia(PCPL E. HAZEL, N. SETHI, G.JACDUETTE, J. DDBKIN. Harlem Hospital and Columbia U. College of Physicians and Surgeons, New York, N.Y. ST therapy of PCP has been reported to produce frequent and severe toxicity in mainly white AIDS patients(pts). In 54 pts (53 blacks) with AIDS treated for PCP no ST rashes occurred. Une white pt had mild rash due to oxacillin. Neutropenia(NP) was less frequent and milder and began later than reported previously despite the normally lower white blood oounta48 hrs 2 3 Platelets <4OK 1 1 WBC <750 5 1 Methemaglobin >20 - 1 LFT's 5X nl 6 1 Nausea & Vomiting 2 2 In lst episode PCP, oral D and S are equally effective. S showed higher incidence of major toxicities ('WBC,fLFT's) p=.0049. Outpt therapy is appropriate for pts with p02 360. Frequent laboratory monitoring is required in the 2nd week of therapy. 208 F.3-4 Infectious Causes of Diarrhea in Patients (pts) with AIDS. MA ANTONY, LJ BRANDT, ROBERT S KLEIN, LH BERNSTEIN. Montefiore Medical Center, Albert Einstein College of Medicine, Bronx, New York, U.S.A. We retrospectively reviewed the records of 100 pts with AIDS to determine the rate and spectrum of microorganisms producing diarrhea in this syndrome. 64 pts had diarrhea documented. Diarrhea occurred in 28/35 homosexual or bisexual men (802) compared to 37/64 heterosexual subjects (582) (p< .05). An infectious cause of diarrhea was found in 36/64 (562). 11/36 (311) were found on ova & parasite examination, 8 by stool culture, 4 by acid fast smear of stool, A by histological examination of a colon biopsy specimen, and 9 by any combination of these methods. Simultaneous enteric infections occurred in 9 pts. Enteric pathogens identified included Mycobacterium avium-intracellulare (MAI) in 9 pts, cytonegalovirus (6), cryptosporidium (5), salmonella sp. (5), Herpes simplex (3), candida (2), Isospora belli (2), Strongyloides stercoralis (Z), and 1 each of Giardia lamblia, Schistosoma mansoni, Entamoeba histolytica, hookworm, Blastocystis hominis, Aeromonas hydrophila, Clostridium difficile, Campylobacter jejeun , and adenovirus. Blood cultures were positive in 19 pts. Isolates included MAI (10), salmonel- la sp. (5), Campylobacter jejeuni (2), and shigella (2). In 4/5 pts with sal- monella and all with campylobacter or shigella, stool cultures were negative. In 16 pts with a microorganism identified in stool, tissue, or blood, initial evaluation for the diarrhea led to the diagnosis of AIDS. In the remainder of those with infectious diarrhea, the diarrhea occurred at a mean of 7.7 months (range 1—27) after the diagnosis of AIDS. This study demonstrates that infectious diarrhea is common in pts with AIDS. Gastrointestinal infections associated with diarrhea are often multiple (251). MAI is the most commonly identified cause of diarrhea in our pts. Diarrhea in AIDS occurs more commonly in homosexual or bisexual men than in heterosexuals. AIDS and AIDS Related Complex: Oral Manifestations and Treatment F.3.5 MARIO ANDRIOLO, JR., St. Clare's Hospital and Health Center, New York, NY, USA Fifty (50) people with AIDS/ARC, undergoing dental treatment, were evaluated for AIDS related infections and malignancies in the oral cavity. Candidiasis was the most common manifestation (53%), with the lateral borders of the tongue usually involved. Other sites were the floor of the mouth, palate, buccal mucosa and pharynx. Treatment consisted of several anti-fungal drugs, depending on severity and longevity of infection. Oral Kaposi's sarcoma lesions (32%) showed the palate and gingiva as the most common sites, while tongue and tonsillar involvement was seen. Lesions that interfere with patient comfort and function may require chemotherapy, radiation, laser or surgical treatments. Hairy leukoplakia (23%) was seen alnnst exclusively on the lateral borders of the tongue, with one case on the buccal mucosa. All but one patient had superimposed candidal infections or a history of candidiasis. Treatment could include anti—fungal and/or anti-herpetic drugs, although lesions seem to regress and recur independently. Gingival and periodontal problems (20%) included gingival pain resembling acute necrotizing ulcerative gingivitis (ANUG) and accelerated deterioration of pre—existing periodontal conditions. Acute infections required antibiotic therapy, but gentle debridement and careful scaling and root planing eliminated most problems. Stomatitis (12%), seen here as a chronic infection, can be painful and debilitating. Herpetic gingivostomatitis, on the keratinizing and non—keratinizing mucosa, was treated with anti-herpetic drugs and major apthous ulcerations responded to topical antibiotics. No oral manifestations were seen in 12% of the patients, F 3.6 The Value of Liver Biopsy in the Diagnosis of Mycobacterial Infection in AIDS Patients DAVID S. RUBIN, G.S. SIDHU, W. EL-SADR, M.S. SIMBERKOFF. NYVAMC, New York, NY Sixty-five liver biopsies(vax) from patients with AIDS were reviewed. We analyzed pathological(path), microbiologic cultura(Cx) and liver function tests (LFTs). Biopsies were divided into 3 groups: Group(Gp) A(23 pts) had positive path and/or Cx for acid fast bacteria(AFB) in the vax(all M.avium—intrsce11ul— g£g[MAI]); 13/26(56Z) had granulomata(10 were poorly formed), 7/23(30%) had hepatitis, both portal and lobular. Gp B(18 pts) having negative AFB on path and Cx in liver but Cx positive in bronchial f1uid(13),blood(3),1ymph nodes(3), bone marrow(2),urine(l),spleen(1) and colon(1). Fourteen pts had MAI,3MTb, l M.gordonae and 1 M.kansasii. Poorly formed granulomata were seen in 2 and hepatitis in 16. Cp C(23 pts) had no evidence of AFB from any site(13 vax with hepatitis,4 with granulomata,1 with lymphoma and 5 normal). The meanzS.D. for alkaline phosphatase was 6431711,1952239 and 2411190 mU/ml for Cp A,E and C, respectively. There was a significant difference between slk. phos. in Gp A and Gp B(p(§02) and Gp A and Gp C(p=.0148). There was a significant association between granulomata and AFB in vax(p(.001). Mycobacteremia was associated with AFB in vax(p(.01), but in 5/17(29Z) in Gp A blood st were negative and thus would not have indicated the presence of AFB disease. The yield of AFB was 15/30(50%) in blood,23/Al(56z) in vax and 26/31(83%) in bronchial secretions. vax was helpful in the management in 32/65(49%) of pts. We conclude that vax may speed the diagnosis of disseminated AFB(in 13/23 the diagnosis was rapidly evident on path). Granulomata on vax, albeit poorly formed, and elevated alkaline phosphatase were both strongly associated with AFB in the liver. FRIDAY, JUNE 5 Immunology—Immunopathogenesis F'4_1 Influences of Related Retroviruses on Human Lymphocyte Functions Mn R. PAHWA“, R.A. GM)“, C. SAXIMEI-IRfl", *North shore university Hospital, Cornell University Medical College, Manhasset, NY, **All Children's Hospital, University of S. Florida, St. Petersburg, FL, "*National Cancer Institute, Bethesda, MD. Infection with the human immunodeficiency virus (HIV) can lead to profound perturbations of the immune system as well as to clinical disease. In contrast, two related retroviruses, the human lymphotropic virus type Iv (H'nN—IV) and the Simian lymphotropio virus type III (SEN-III) have not been associated with clinical disease in their infected hosts. In this study, these viruses were grown up in the Hut-78 cell line, concentrated, band-purified and disrupted. Protein-rich preparations of these viruses were compared for their influences on functions of B- and T lymphocytes of healthy, HIVFuninfected donors. As described previously, the HIV protein preparation could induce a T—dependent, polyclonal response in B lymphocyte cultures resulting in hnmnxglobulin secretion. In contrast, the other two viral preparations did not cause either proliferation or differentiation of normal B 1 es. Pokeweed mitogen-induced B cell differentiation responses were inhibited in a dose-dependent manner with HIV but minimally with REV-IV or S'I'LV—III. None of the viral preparations induced a blasto- genie response in peripheral blood lymphocyte cultures. T lymphoproliferative responses to mitogens, antigens and allo-antigens were inhibited sanewhat immsistmtly and to varying degrees by these viral preparaticms, but most regularly with HIV. These findings suggest that these viruses differ in their capacity for causing immmologic dysfmctim. F 4 2 Homologous Peptides From HIV P41 and HLA CLASS II Bind CD4 on ' ' Human T Cells HANA GOLDING, FRANK A. ROBEY, FREDERICK T. GATES, III, WOLFGANG LINDNER and BASIL GOLDING, NCI, NIH; DB? and DBBP, FDA; Bethesda, MD 20892. The CD4 molecule has been identified as the receptor for HIV envelope protein. Recently, the possible natural ligand for CD11 on antigen presenting cells has been localized to the ,8—1 domain of MHC class II. It was postulated that the MHC class II and HIV bind the non‘dpolymorphic CD4 via similar conserved regions. A hydrophilic septamer was identified displaying a high degree of homology be— tween p41 of HIV and the 8-1 domain of HLA—DR and -DQ. Both the HIV and MHC class II derived septamers were synthesized. Incubation of these peptides, but not control peptides, with CD4 positive cells at 37°C for 45 min resulted in reduced binding of anti—CD4 antibodies (0(1'4, (KT/la, Leu3) to the cells. lhis reduction of binding to CD4 could be blocked in the presence of chloroquin. Binding of antibodies directed against other surface antigens, were unaffected by pre-incubation with the peptides. The temperature requirement and sensi- tivity to chloroquin suggest that the peptides induced partial modulation of the CD4 molecules via receptor mediated endocytosis. In addition, flow cyto— metry showed that biotinylated chicken albumin conjugates of the peptides can bind directly to CD4 bearing CEM cells, but not to a (:04 negative CEM mutant or to B cell lines. 'lhis binding could be partially inhibited in the presence of mouse monoclonal anti—€04 antibodies. In addition, solubilized GEM mem— branes were passed over a column of immobilized HIV—derived peptide. The bound material which was eluted with the soluble peptide contained a 57,000 dalton material which was positively stained with (1(T4 + (1(T4a reagents using Western blot analysis. These findings suggest that, the homologous regions of HIV and MHC class II, which we have identified, may be the sites involved in binding of AIDS virus and Ml-IC class II antigens to CD11 on human T cells. HLA-DR is Involved in the HIV Receptor DEAN L. MANN, F LESANE,NA BLATTNER, M POPOVIC, National Cancer Inst1tute, Bethesda, MD. Cells procured from human tissues that can be infected with HIV express both the CD4 molecule and major histocompatibility class (MHC) class II antigens. We therefore, investigated the interaction of HIV with cell surface CD4 molecules and (MHC) II antigens. Exposing whole virus preparations for 15 min to a cultured T lymphocyte line and phytohemagglutinin (PHA) stimulated peripheral blood lymphocytes (PBL) resulted in a decrease in the CD4a epitope and in HLA- DR cell surface antigens while HLA—DP and HLA-DQ increased or remained unchanged. After 120 min of virus exposure, the CD4a epitope remained diminished while HLA-DR returned to the levels of detection found on cells not exposed to virus. The specific portion of HIV that binds the CD4 molecule has been shown to be the large envelope protein, gp120. When immunopurified gp120 was added to PHA stimulated and unstimulated PBL, the CD4 epitope decreased in the same manner as was observed with whole virus preparations. However, in contrast to the binding of whole virus preparation, HLA-DR expression increased after 15 min of exposure to gp120. These studies show that HLA-DR and the CD4 molecule are involved in the receptor for HIV binding and suggest a dynamic role for a CD4-HLA-DR complex in HIV attachment to target cells. F.4.3 209 F 4 4 Altered IL-Z Gene Expression in HIV Infected Peripheral Blood ' ' CD4+ Lymphocytes: Possible Mechanism for Virus Induced T Cell Death for the Inmunopathogenesis of AIDS H. CLIFFORD LANE*, M. DUKOVICH**, S. MCCARTHY*, A.S. FAUCI*, w. GREENE**. *Nationa Institutes of Health, Bethesda, MD, **Howard Hughes Medical Institute, Duke University School of Medicine, Durham, NC. The peripheral blood lymphocytes of patients infected with HIV exhibit a variety of immunologic abnormalities the most consistent being a decrease in the number and function of CD4+ T lymphocytes. Several mechanism have been postulated to account for this defect HIV envelope protein induced cell fusion, and the intracellular accumulation of non-integrated viral DNA. The present study was designed to determine the effects of HIV infection on IL-2 gene expression in CD4+ peripheral blood lymphocytes. IL-2 production, a protein since this protein plays a central role in T cell growth and differentiation. Purified peripheral blood CD4+ lymphocytes were infected with HIV and maintained in culture for 14 days. Non-infected cells were maintained in culture as a control. On various days following infection cells were removed and stimulated for 12-18 hours with PHA/PMA. These cell cultures were assayed by FACS analysis, in situ hybridization and northern blot hybridization. C04+ cells infected with HIV progressively lost the CD4 antigen, while retaining CD3 reactivity with virtually all cells being CD3+/CD4- by day 14. Northern blot analysis revealed that cells infected with HIV underwent a progressive and marked reduction in IL-2 gene expression. In contrast the expression of the IL-2 receptor on several other cellular genes was not altered by HIV infection. This pronounced inhibition of IL-2 gene expression induced by HIV infection may contribute to the death of CD4+, the lymphocytes in patients with AIDS. F 4 5 A Synthetic Peptide Homologous To HIV gp120 Envelope Glycoprotein ' ' Inhibits IL—z Production. 'I‘_. C_.CHANH, B. 1:. ALDERE'I‘E, c. D. FRENZEL, G. R. DREESMAN, R. C. KENNEDY, P. KANDA. Southwest Foundation for Biomedical Research, San Antonio, Texas. We have chemically synthesized a peptide homologous to sequence 304-321 of the HIV gp120 envelope glycoprotein. Peptide 304-321 was found to decrease the production of IL-2 of a gibbon cell line MIA-144. Phytohemagglutinin-induced IL-2 production by normal human peripheral blood mononuclear cells was also reduced in the presence of peptide 304—321. Incubation of the IL-2 dependent murine I‘LL-2 with peptide 304-321 resulted in a decrease in the uptake of H-thymidine, whereas control peptides have no effect. HIV peptide-induced inhibition of CTLL-Z proliferation could be partially restored by addition of exogenous IL-Z. Peptide 3011-321 had no effect on the expression of IL-2 receptor (IL-2r) since peptide-treated and -untreated cells express comparable amount of IL- 2r as detected by immunofluorescence using a monoclonal antibody to IL-2r. These data together with recently published results on viral induced- immunosuppresion support further studies in the role of HIV envelope glycoprotein in the immunodeficiency observed in AIDS. I: 4- 5 PERIPHERAL BLOOD ADHERENT CELLS FROM AIDS PATIENTS INHIBIT NORMAL T— CELL COLONY GROHTH THROUGH DECREASED EXPRESSION OF INTERLEUKIN Z-RECEPTORS AND PRODUCTION OF INTERLEUKIN 2. v. LUNARDI- IsyNDAR’H v. GEORGOULIAS" ,* o. VITTECOQ", F. BARRE-SINDUSSI***, J. C. CHERMANN C. JASMIN et al.1l1SERM U 268, Hop. Paul Brousse, B.P. 200, 94804 Villejuif CEdex, Flippers ; Service des maladies infectieuses, Hop. Saint Louis, PARIS and Dpt of Virology, Institut Pasteur, PARIS, France. Colony formation in semi-solid media from peripheral blood T-cell colony- forming cells (T- CFC) of AIDS patients is extremely impaired. To define whether the low plating efficiency is due to inhibition mechanisms or/and to decreased clonogenicity of T- CFC, patientsI peripheral blood mononuclear cells (PBMC) were fractionated into T-cell enriched and T-cell depleted subpopulations. Both cell fractions failed to generate T cell colonies although colony growth could be obtained from unfractionated PBMC. In 5 out of 12 AIDS patients, adherent cell-depletion of PBMC enhanced the plating efficiency. Moreover. patients' but not normal adherent cells could inhibit normal T-cell colony growth in a dose- -dependent manner. Media conditioned by patients‘ unstimulated adherent cells (LCM—A+p) also inhibit normal T-cell colony formation. In addition, LCM-A+p could inhibit interleukin Z-receptor (ILZ-R) expression and Interleukin 2 (1L2) production by normal mitogen-stimulated T cells. These LCM-A+p did not contain detectable reverse transcriptase activity or could not infect the Human Immunodeficiency Virus (HIV)-permissive T-cell line CEM. Conversely, this adherent-cell-derived inhibitory activity could be abrogated by both heating and treatment with proteolytic enzymes. These findings indicate that the low T-cell colony formation in some AIDS patients could be due to inhibitory adherent cell-derived activities. FRIDAY, JUNE 5 F.5.1 Confidentiality and the Duty to Protect: in the Case of AIDS RONALD BAYER, CAROL LEVINE and SUSAN M. WOLF, The Hastings Center, Hastings— on—Hudson, N.Y., USA. Autonomy--the right to control one's own life, including the right to privacy-—is a basic ethical principle. In the case of HIV infection, which can be transmitted through sex and blood to others, autonomy comes into conflict with the harm principle--the obligation to prevent harm to others. There are both legal duties to protect third parties placed at riSk by a person with HIV infection and moral duties, and the two are not necessarily coextensive. This paper explores the moral duties, in comparison to the legal ones. It presents an ethical framework for guiding physicians and health care providers, public health officials, and others who have knowledge of a person's HIV infection. The paper considers clinical, residential or institutional, and public settings. It addresses such questions as: How ought physicians and health care providers respond when HIV-infected individuals refuse to notify their sexual or drug-using partners? What are the moral, professional, and social costs of breaches of confidentiality, compared to the possible benefits of notification? What kinds of public healthprogram can protect the interests of those already infected, those who may be infected, and those currently at risk? The Limits of Autonomy Ethical Dilemmas Inherent in HIV Antibody Testing Legislation: A One Year Retro— F.5.2 spective NANCY J. KAUFMAN. J. VERGERONT. H. FRlSBY. Wisconsin Division o1 Health. Madison. Wisconsin In November. 1985. the Wisconsin Legislature enacted unique legislation. protecting the confi- dentiality and rights of persons with HIV infections while protecting the public's health by re- quiring HIV antibody-positive case reporting. Provisions include HIV testing informed written con- sent procedures. a specific listing of persons to whom test results may be disclosed. reporting of positive. validated test results to the state epidemiologist. restrictions on the use of antibody test results for insurance underwriting and employment. and civil and criminal penalties for un- lawful disclosure. Ethical dilemmas faced by the bill's drai‘ters were the following: 1) Would confidentiality/con— sent procedures and reporting requirements deter physicians irom testing7 2) Would reporting of antibody-positives deter individuals from seeking testing? 3) Would physicians comply with re- porting requirements? Data collected from alternate sites and Wisconsin‘s public health laboratory were analyzed one your post implementation to determine antibody testing practices, patterns. and reporting effica- cy. 0f the 4.487 antibody tests performed. 575 were from private physicians. indicating their willingness to participate in the program and the willingness of at-risk individuals to be tested without anonymity. Of persons tested by private practitioners. 4.6! were western-blot positive. compared to 7.5% positivity for those tested at alternate sites. The reporting requirement of the new law may have encouraged higher risk individuals to seek anonymous testing. Use of alternate sites and private physicians has increased steadily. irrespective of the legislation. 0“ the 117 positives tested by private physicians. 71$ (8}) were reported to the state epidemiologist. Can» pliance is adequate for first year implementation. Public policy makers need to consider the effect that HIV antibody testing legislation will have on encouraging at-risk individuals to seek testing. counseling. and medical supervision. Miscon- sin data indicate that such legislation did not deter individuals from seeking assistance. AIDS: Transfusion and Litigation BARR, DUNCAN.l .J.D.z LISA '1'. UNGERER, J.D., SUSAN J. RIEFEL, J.D., O'CONNOR, COHN, DILLON & BARR, San Francisco, California Concurrent with the medical disaster presented by the spread of AIDS is the filing of lawsuits by individuals who have been exposed to or have contracted AIDS through blood transfusions or use of Antihemophilic Factor VIII. The authors are currently defending approximately fifty such lawsuits. In some instances, hemophiliacs have brought lawsuits in the form of class action, wherein the class action representative claims to represent the interest of all hemophiliacs claiming similar injuries. No Court to date has allowed this type of action; if this occurs, it would have a detrimental effect on all AIDS patients because of the invasion of privacy and interference with the physician/patient relationship. While HIV antibody tests are now used by all blood banks and plasma centers, the number of transfusion related AIDS cases will continue to increase because of the incubation time between exposure and onset of symptoms. Litigation is growing in tandem with reported cases of AIDS. The very future existence of non-profit volunteer blood banks is in question as insurance for AIDS lawsuits is now unavailable. The authors address the future of TAA litigation and the future question of the obligation and ethics of blood banks in contacting the recipients of blood obtained from individuals who, subsequent to blood donation, test positive for HIV anti— body. 210 F 5.4 Anti-Discrimination Legislation and the Reduction of Social Disruption Caused by AIDS GREGORY J. TILLETT, New South Wales Anti—Discrimination Board, Sydney, Australia Extensive community fear of AIDS has led to widespread discrimination against people who have or who are perceived to have AIDS, especially in the area of employment, but also in service provision (including health and welfare services), accommodation and education. Breaches of confidentiality, invasion of privacy and violation of duty of care have also been reported. Anti-discrimination and human rights legislation has been used in an attempt to protect the rights of those who have been subjected to AIDS-related discrimination. In some cases, pre—existing legislation has been used, in others, AIDS- specific legislation has been introduced. Ten cases of AIDS-related discrimination are surveyed, and four cases analyzed in detail to assess the effectiveness of such legislation. By itself, legislation does not enable problems based on fear of a terminal illness or prejudice against a traditionally stigmatized minority to be resolved. Legislation, however, provides an important symbolic and statutary support for attitudinal change through education. F_5 5 Legal and Ethical Analysis of Insurance Underwriting for AIDS BENJAMIN SCHATZ, ESQ., Director, AIDS Civil Rights Project, Nat- ional Gay Rights Advocates, San Francisco, CA. Presents results of article which will appear in June '87 Her- vard Law Review. Reviews approaches used by insurance companies to eliminate applicants at high risk for AIDS, and evaluates theirle- gal and social impact. Concludes that insurers have legal right to exclude applicants diagnosed with AIDS or ARC. Attempts by hwurers to eliminate all gay male applicants are also documented, and are shown to violate state insurance laws, recommended policy of Nat- oinal Association of Insurance Commissioners, and state and local law prohibiting discrimination in public accomodations. Such eff- orts also increase employment discrimination, decrease candor of gay and bisexual males towards physicians and sexual partners, and increase financial burden on govt. programs such as Medicare, Medi- caid and public hospitals. Use of HIV antibody test results by insurers is shown to violate laws or insurance department policies in 13 jurisdictions. Legal precedent for such laws exists in 11 states which prohibit genetic testing by insurers. HIV antibody testing by insurers is demonstra ted to discourage voluntary testing, deter participation in res— earch studies, and impede vaccine trials. Such testing also viol- ates F.D.A. labeling of the test, omits the crucial component of counseling, and cannot be guaranteed to be confidential. Financial argument used by insurers to justify testing is shown to be'exagg- erated. F.5.6 Municipal AIDS Discrimination Laws as Public Health Ed— ucation Tools for Preventing HIV Transmission DAVID I; SCHULMAN*, M. KARP**. N. NICKENS‘**, Los Angelea City Attorney's Office, **New York City Commission on Human Rights, ***San Franciscio Human Rights Commission. In August 1985. the Los Angeles City Council passed the na— tion's first AIDS discrimination law, receiving national media attention, and later created a special AIDS Discrimination Unit. Similar units have since been created in San Francisco and New York. The authors, heads of these three units, have handled hundreds of AIDS discrimination complaints in the employment, housing, education, government, business, dental and medical service areas. The vast majority have been handled without litigation due to their philosophy of early intervention and mediation of these disputes. This paper examines the nature of AIDS discrimination disputes and how they relate to attitudinal change about AIDS. It addres- ses the ways in which the public's desire to obey local AIDS discrimination laws can be used as effective public health education tools for compelling citizens to learn about HIV transmission. The role of stigma and taboo are discussed as they affect early intervention and mediation of disputes. Specific cases concerning funeral societies in New York and the dental profession in Los Angeles, as well as related San Francisco cases will be studied to reveal the importance of locally-based, full-time government attorneys experienced in community organi— zing principles in successfully conducting such intervention. FRIDAY, JUNE 5 Epidemiology—Other Retroviruses F 6-1 Lymphadenopathy Associated Virus Type 2 (LAV2) - Seroepidemiological Study in Cape Verde islands. FRANCOISE BRUN—VEZINET', C. KATLAMA‘, D. CEUNINCK*“, D. ANDRADE', D. DARIO", M.A. REY, et a1.*Hopital Claude-Bernard, Paris, France, "Delegado da Saude, Santiago, Cape Verde. A new human retrovirus (LAV2/HIV2) was isolated from an AIDS patient from Cape Verde Islands; therefore we designed a seroepidemiological study to evaluate the presence of HIV2 infection in this country. In the main island, Praia-Santiago, 236 subjects (217 males, 19 females) were tested : 93 soldiers. 110 prisoners, 13 blood—donors and 20 hospitalized patients. In the second island. Sal, sera were taken from 144 subjects (67 males, 77 females). All sera were tested for antibodies to HIVl (HIVl-Ab) and HIV2 (HIV2-Ab) by Elisa and confirmed by Western blot. In Sal, all sera were negative for both HIVl—Ab and HIVZ-Ab; in Praia, all were HIVl-Ab G and 15/236 were HIVZ-Ab 0 z 13 were healthy subjects (2 soldiers, 9 prisoners and 2 blood—donors) and 2 women had clinical symptoms consistent with AIDS. None were homosexual men nor drug addicts. 7/15 had previous history of sexually transmitted diseases (STD) (7 patients) or transfusion (1 patient). No significant difference was found between the 9 HIV2-Ab a and the 101 HIV2-Ab 9 prisoners considering mean age (29.6 years vs 27.6), previous transfusion (1/9 vs 4/101), STD (5/9 vs 40/101) or travel to other African countries (1/9 vs 3/101). 4/15 HIV2-Ab 0 sera were completely negative by HIV1 Elisa. This study assessed the presence of HIVZ infection in Cape Verde islands; heterosexual contacts seem to be the predominant route of HIV2 transmission. Moreover HIVl Elisa can miss HIV2 antibodies. Therefore blood-bank screening as seroepidemiological surveys must include, at least in Western Africa, both HIVl and HIV2 assays. Prevalence of HIV and STLV-III related human T-lymphotropic retrovirus (HTLV- IV) in several populations of Ivory-Coast. Nest—Africa. G. LEDNARD‘, F. BARIN“, A. SANGARE'*', G. GERSHY—DAMET”*, J.L. REV***, F. DENIS‘, et al., ”CHO Dupuytren, Limoges, France, *‘ CHU Bretonneau, Tours. *** Institut Pasteur and INSP. Abidjan, Ivory-Coast. The sera from 2900 individuals were collected from January to December 1986 in six geographic areas of Ivory Coast. Sera were tested for antibody to HIV by a commercially available ELISA (Abbott). All the sera which gave a ratio sample absorbance /cut-off value over 0.80 were subsequently tested by two western—blots using either HILV-IIIB or MTLV-Iszag as antigenic probes. The results indicate that both viruses. HIV and STLV-III related human retrovirus- HTLV-IV-, are widely present in Ivory-Coast. Briefly the results are as follows : - In control populations (without any risk factor) including 300 children and 850 adults, the adult prevalences were 2.7 I for HIV and 0.4 I for HTLV-IV. - In populations with risk factors were included : . 350 patients receiving multiple injections. The prevalences were 6.1 X for HIV and 1.8 I for HTLV-IV 1200 individuals having multiple sexual partners (prostitutes. prisoners. ...). The prevalences were 8.9 1 for HIV and 9.9 I for HTLV-IV. 2.9 1 had serological evidence of exposure to both viruses. . 200 inpatients presenting with pulmonary infections associated with asthenia and weight loss (considered as AIDS related symptoms). The prevalences were 19 x for HIV and 8 x for HTLV-IV. 13 1 had antibodies to both serotypes evidenced by reactivities to envelope glycoproteins of HTLV-IIIB and HTLV-IV. The coexistence of both HIV and STLV-III related retrovirus —HTLV-IV- in Ivory Coast le allow prospective studies providing important information: on the natural history of diseases associated with these two viruses in Africa. F.6.2 F 6 3 LAVZ/HTLV IV INFECTION ADKINS BLOOD DONORS. wLTITRANSFUSED ' ' I DF IDS I GROUPS, F N , A.N. COUROUCE - cfi. FWZIOUX - F. ERIN - S. CWEI and the RETROVIRUS study group of the french society of blood transfusion — Paris FRANCE - Since the discovery of a 2nd virus responsible for AIDS in Nest-Africa, 5 blood donors have been found LAVZ/HTLV IV seropositive in different french blood banks during 1986 : - A man from Senegal with multiple heterosexual partners - A french man living with a LAVZ positive woman from Ivory Coast - A french heterosexual man and I.V. drug user, having stayed in Ivory Coast. - An heterosexual man from Ivory Coast living in France for 4 years, - The french wife of a LAV2 positive man from Ivory Coast. All of them have been detected thanks to a positive reaction by LAVI Elisa. They gave unusual pattern by Western-Blot analysis (HB)= clear bands on p25 and p34 only. They were strongly positive by HB—LAVZ (Diagnostics Pasteur) and RIPA—LAVZ. In addition, a multi-Centre study has been made by Elisa LAVZ (Diagnostics Pasteur) on 1145 sera 210 polytransfused patients, 167 hemophiliacs, 452 IV drug users, 123 subjects from Africa and 193 sera which recognized only core proteins (p18 or p25) by HB. None of them have been found LAV2 seropositive. These results suggest a Nest African localisation for this second AIDS virus and a very low prevalence of this virus among blood donors collected in France. Further studies on over 9000 blood donors are in progress. 211 F.6_4 Transmission of HTLV-I and HIV Among Homosexual Men in Trinidad. WILLIAM A BLATTNER*, F CLEGHORN**, wc SAXINGER*, B MAHABIR***. B HULL-DRVSD'AEE’I‘“, (5 BAR HOLOMEN“. *Natl Cancer Institute, Bethesda, MD 20892, "The General Hospital, and "*Caribbean Medical Centre, and ****Pan American Health Organization, Port-of-Spain, Trinidad. Risk factors for HTLV-I and HIV infection were evaluated among a cohort of 100 homosexual/bisexual men in Trinidad. The high seropositivity for HTLV-I (15%, a six-fold increase compared to general population rates) and the finding that duration of homosexuality and number of sexual partners were associated with increased seropositivity suggested that HTLV-I like HIV can be transmitted by homosexual sex. Forty percent of homosexuals conpared to 0.19% of a general population comparison group were seropositive for HIV, and sexual contact with U.S. men was the major risk factor. Prior history of gonorrhea, a marker of sexual promiscuity, was associated with HIV seropositivity as well. HIV seroprevalence was three times higher than that for HTLV-I, suggesting that HIV is more efficiently transmitted, especially since HIV appears to be recently introduced into Trinidad while HTLV—I is endemic. Markers of altered inlnune status were most perturbed in 6 study subjects coinfected with HTLV-I and -111. One case of HTLV-I-associated adult T-cell leukemia (ATL) in an HIV infected homosexual raises the possibility that HIV coinfection accelerated the pathogenesis of clinical ATL. Interactions between human retroviruses may amplify their clinical effects, a hypothesis that will require further consideration in populations and in areas where nultiple human retroviruses occur. F65 Emerging High Rates of Human T-Cell Lymphotropic Virus Type I (HILV-I) and HIV Infection Among U.S. Drug Abusers (DA). STANLEY H. WEISS*, H.M. GINZBURG*, w.c. SAXINGER*, K.P. CANTOR*,F.K. MUNDON**, D.H. ZIMMERMAN**, H.A. BLATTNER*. *National Cancer Institute, Bethesda MD, **Electro-Nucleonics, Inc., Columbia MD. HTLV-I is associated with adult T-cell leukemia (ATL) in Japan and in populations of African ancestry in the Caribbean basin and bordering areas including southern U.S. blacks. Endemic virus infection is observed in areas where ATL may account for >50% of adult non-Hodgkin's lymphoma. Surveys of U.S. populations document low or absent HTLV-I seroprevalence in most study groups. Following-up our finding of 16% seropositivity for HTLV-I among Queens, NV DA (JAMA 255:3133), we surveyed 963 New Jersey (N.J.) and 214 New Orleans, LA (N.0.) DA. Sera were screened for HTLV-I antibodies by ELISA and confirmed by immunofluorescence, competition and/or immnoblot. SEROPREVALENCE BY LOCATION AND RACE BLACK DA NON-BLACK DA SITE (year) HTLV-I HIV 80TH HTLV-I HIV BOTH N.0. (1985) 49.3% 0.0% 0.0% 6.6% 2.6% 1.3% N.J. (1984) 30.2% 45.0% 15.5% 8.5% 31.0% 3.2% Black DA were significantly more likely to be HTLV-I seropositive than whites or Hispanics. Almost 50% of black N.0. DA were HTLV—I positive but HIV was absent suggesting that HTLV-I is an older endemic virus in this population. The elevated HTLV-I infection rates in the non-black DA raise the possibility that new spread of HTLV-I is emerging as a consequence of paraphernalia sharing. There are potential public health implications of this trend including long term sequelae such as lymphomas/leukemias and neurologic diseases, heightened risk to the blood supply, and potential for adverse modification of HIV natural history from retroviral co-infection. E65 HTLV-IV and HTLV-III/HIV in West Africa PHYLLIS KANKI*, S. M'BOUP**, F. BARIN***, D. RICARD*, F. DENIS****, M. ESSEX*, et a ., FHarvard School of Public Health, Boston, MA, ”University of Dakar, Dakar, SENEGAL, ***University of Tours, Tours, FRANCE, ****Univer- sity of Limoges, Limoges, FRANCE. A new human T-lymphotropic virus has been recently described from healthy Nest Africans. A unique feature of preliminary studies with HTLV-Iv indicated that in contrast to HTLV-III/HIV it was not associated with classic AIDS or related disorders. We present data on 4,248 serum samples from Senegal, Guinea, Guinea Bissau, Mauritania, Burkino Faso, and Ivory Coast. Control, sexually active risk and disease populations including AIDS were sampled from 1985 to 1987 and analyzed for reactivity to HTLV-IV and HTLV-III/HIV by radio- inununoprecipitation and SDS/PAGE and immunoblotting. Evidence for HTLV-IV infection was found in 5 of 6 countries, however the seroprevalence rates varied markedly (Ix-32% overall). Healthy sexually active risk groups demon- strated higher levels of HTLV-IV infection compared to healthy control and disease groups including AIDS. The seroprevalence of HTLV-III/HIV infection also varied from country to country and highly correlated with the rare cases of AIDS diagnosed; seroprevalence for HTLV-III/HIV was uniformly lower than that of HTLV-IV. It is not clear if HTLV-IV is a completely non-pathogenic HTLV, however the biology of this virus infection shows marked differences from that of HTLv-III/HIV and the pathogenesis of AIDS. The existence of at least two cross-reactive HTLVs in many countries of West Africa indicates the necessity for distinguishing serologic assays such as RIP-SDS/PAGE and immuno- blot analysis. Present data indicates HTLV-IV is not correlated with AIDS or other related disorders. This points out the need for health policy that will address issues of prevention and control for T-lymphotropic viruses of differing pathoggnicity. FRIDAY, JUNE 5 Virology—Animal Models Infection of Rhesus Macaques with HIV—2. F'7'1 PATRICIA N. FULTZ*, WILLIAM M. SWITZER*, and LUC MONTAGNIER**, *AIDS Program, Centers for Disease Control, Atlanta, GA, **Institut Pasteur, Paris, France. We have attempted to infect rhesus macaques with four different isolates of human immunodeficiency virus type 2 (HIV-2, originally called LAV-Z). Eight macaques, ranging in age from 18 months to 5 years, were given intravenous in— jections of cell-free virus using the ROD and MIR isolates. Fourteen weeks after inoculation, three animals received a second injection of virus. At time of rechallenge, one rhesus had serum antibodies to £5! gene products, gp140 and gp34, which we detected by immunoblot and radioimmunoprecipitation assays. within 7 weeks of the second inoculation, two other macaques had seroconverted with antibodies to gp34 and gplAO; however, virus had not been isolated up to 9 months after the initial injection of virus. More recently, two additional HIV—2 isolates, EHO and DIA, were each injected into one rhesus 3 days after xenogeneic stimulation of the animals with 107 human lymphocytes. Virus was isolated from peripheral blood mononuclear cells of the rhesus that received EHO at both 2 and A weeks after inoculation, but serum was antibody negative both times. These data suggest that the EHO strain of HIV—2 may be more infec— tious for macaques than other isolates tested. We have injected EHO recovered from rhesus PEMC into additional animals to determine whether infections can be established readily with this strain of HIV—2. A model system using macaques and the human virus HIV-2 would be extremely important in developing a vaccine against HIV, since a wider range of experimental vaccines could be tested than is feasible with the more limited chimpanzee-HIV system. F 7 2 Response of Pig—tailed Macaques to SIV/SMM Infection I ' HAROLD M. MCCLURE*, D.C. ANDERSON*, R.B. SWENSON*, J. ORKIN*, E.A. STROBERT*, AND P.N. FULTZ**, *Yerkes Primate Research Center, Emory University, Atlanta, GA, **AIDS Program, Centers for Disease Control, Atlanta, GA. A pig—tailed macaque, inoculated IV with SIV/SMM, developed a viremia that persisted until death 14 months post-inoculation (PI). The animal had chronic diarrhea, lymphadenopathy, lymphopenia and thrombocytopenia and terminally was anemic and ataxic. Autopsy revealed emaciation (22% wt. loss) and generalized lymphadenopathy and splenomegaly. Histology revealed lymphoid depletion and multinucleated giant cells in lymph nodes, spleen, intestine, brain and most other tissues. The animal also had cryptosporidiosis, and retrovirus was isolated from multiple tissues, including the brain. Blood transfusions from this animal to 3 other macaques resulted in acute disease in all 3 recipients. Two of these died at 7 and 9 days PI and the third is recovering from a clini- cal disease that included diarrhea, weight loss, anemia, thrombocytopenia and oral candidiasis. Animals which died had generalized lymphadenopathy, spleno— megaly and hyperplasia, hemorrhage and necrosis of lymphoid tissue of the in- testine. Histologically, lymphoid tissues were reactive and contained foci of necrosis and multinucleated giant cells. Bacterial organisms were not isolated or demonstrated by special stains in tissue sections. Three additional macaques were inoculated with a retrovirus isolated from either the initial case or a transfusion recipient. All 3 developed acute disease within 5 days and died within 7—8 days PI. Lesions in all 3 animals were identical to those seen in the transfusion recipients. These observations suggest that SIV/SMM is more pathogenic in the pig-tailed macaque or that the virus has become more virulent after passage in one animal (supported by NIH grant no. RR-00165). F.7.3 Natural and Experimental Infection of Macaques With the Simian Immunodeficiency Virus RONALD C. DESROSIERS, M.D. DANIEL, M. KANNAGI, P.K. SEHGAL, N.W. KING, N.L. LETVIN, et al., Harvard Medical School, New England Regional Primate Research Center, 1 Pine Hill Drive, Southborough, MA. Three of 848 macaques (0.35%) of the NERPRC colony had antibodies to simian immunodeficiency virus (SIV); SIV has now been isolated from these three macaques (two Macaca mulatta and one Macaca fascicularis). Analysis of stored sera and earlier studies have revealed six additional macaques, now dead, who previously were infected naturally with SIV while at NERPRC. Three of these six had lymphoproliferative syndromes/lymphomas. SIV was also isolated from two of these macaques. In one case, in utero transmission was documented. A total of 16 juvenile rhesus macaques have been inoculated with SIV grown in human peripheral blood lymphocytes or in HUT-78 cells. Eight of the macaques died 129-352 days post—inoculation with a variety of clinical and pathologic findings paralleling those of AIDS in humans. The other eight macaques became persistently infected for prolonged periods; these eight macaques remain alive 537-820 days post inoculation despite the continued ability to isolate SIV and persistent lymphadenopathy. The ability to survive infection correlated directly with the strength of the antibody response. There was no correlation of the dose of virus inoculum with either the strength of the antibody response or clinical outcome. Antibodies readily detected by ELISA and by immunofluorescence have been induced in macaques by ISCOM and inactivated virus vaccines; these antibodies recognized the 160/120 kd presumed envelope protein. Vaccinated macaques were not protected against persistent infection by intravenous inoculation of SIV. Additional vaccinations using larger amounts of column purified SIV are in progress in order to define conditions needed to achieve protective immunity. 212 F 7-4 Expression of Human Immunodeficiency virus Long Terminal Repeat in Transgenic Mice. JOHN M. LEONARD*, HOWARD s. GENDELMAN", JASPAL KHILLAN", ADIO Annex-11*, Mom-rs MELTZER"*, HEINER WESTPHAL“, and MALCOLM A. MARTIN’. 'LMM, NIAID; ' LMG, NIAID; National Institutes of Health, Bethesda, MD 20892; and '**Wa1ter Reed Army Institute-of Research, Washington, DC. Transgenic mice were constructed that contain the human immunodeficiency virus (HIV) long terminal repeat (LTR) driving the bacterial enzyme chloramphenicol acetyl transferase (CAT). Independently derived transgenic animals showed a consistent tissue pattern of high CAT expression in thymus, heart, tail, and lens epithelium; intermediate CAT levels in spleen; and no CAT activity in brain, liver, lymph nodes, monocytes, and peripheral blood lymphocytes (PBL). Peritoneal macrophages, stimulated $2 vitro by supernatants from activated murine lymphocytes, showed an 8-fold increase in CAT expression when compared to unactivated cells. when T-lymphocytes from transgenic animals were propagated in the presence of IL-2, a 10-fold increase of CAT activity over unstimulated T-cells was seen. In addition, the stimulated T—cells exhibited an approximately 5-fold further augementation of CAT activity when infected with human adenovirus type-5 or herpes simplex virus type—1. These results show that tissue, immunologic, and virologic factors influence expression of the HIV LTR in these animals. This transgenic mouse system represents a safe and potentially valuable method of evaluate the effects of cellular and viral transactivators on dormant HIV proviruses. F 7_5 The Isolation of a T—lymphotropic Lentivirus from Cats pith an Immunod ficiency Syndrome ** * NIELS c. PEDERSEN , J.K.YAMAMOTO , E.E.SPARGER*, EMA-10*, R.MUNN , UCD School of Veterinary Medicine,**UCD School of Medicine, Davis, CA. A lentivirus, highly tropic for T-lymphocytes, has been isolated from FeLV negative cats with an immunodeficiency-like syndrome. A lentivirus present in the blood or plasma of 3 affected cats was passaged into specific pathogen free (SPF) kittens and then into cultures of ConA and 11-2 stimulated cat lymphocytes. Virus from infected SPF kittens or cultures has been injected into a larger number of SPF kittens, some having been new observed for more than 10 months. Infected kittens developed a transient fever and leukopenia several weeks after inoculation. This was followed by a generalized lymphadenopathy persisting for months. Disease seen in naturally infected cats appeared 1/2 to h years or more after infection. At this stage, generalized lymphadenopathy was not as pronounced, but chronic infections of the nasal cavity, conjunctiva, gums, intestines, skin, ears, and sometimes nervous system, were prevalent. Affected animals survived in ill-health for months or years before dying. Anemia was seen terminally in some naturally and experimentally infected cats. The virus is widespread among cats but is infectious only after prolonged and intimate contact. The feline lentivirus appears antigenically and genetically distinct, but structurally and morphologically similar, to HIV and other animal lentiviruses. Serologic tests confirmed a strong relationship between this virus infection and acquired immunodeficiency. This is the first animal lenti- virus other than those of Old-world primates that has been T—lymphotropic and associated with acquired immunodeficiency-like syndromes. F_7.6 Evaluation of an HTLV-III gp120 Prototype Vaccine in chimpanzees LARRY 0. ARTHUR‘, ".6. N038Y“, 5.". PYLE‘, J.W. BESS, JE.*, P. NARA**, J. KELLIHEH**‘, D. BOLOGNESI, R.V. GILDEN, AND P.J. FISCHINGER, ‘Program Resources, Inc., NOT—Frederick Cancer Research Facility (FCRFL Frederick, MD 21701, *‘Office of the Director, Virus Control Unit, NCI-FCRF, Frederick, MD 21701, Primate Research Institute, Alamogordo, NM 88330, USA. Currently, the only known experimental animal reproducably infectable with human immunodeficiency virus (HIV) is the chimpanzee. We have inoculated chimpanzees with a prototype subunit vaccine consisting of the 120,000—dalton external outer envelope protein of HTLV-IIIb. The gplZO was purified from detergent extracts of membranes of HTLV-IIIb-infected H9 cells by immunoaffin— ity chromatography as previously described (Robey, et al. PNAS pg: 7023, 1986). Experimental animals inoculated with the gp120 prototype vaccine developed antibodies which precipitated the gp120 and neutralized HTLV—IIIb in 13 vitro infectivity assays. The chimpanzees received 4 inoculations, 50 ug each, of gp120 prototype vaccine. All chimpanzees were found to have anti— bodies to gp120 as detected by 125I—gplZO radioimmune precipitation assays and neutralizations of HTLV-IIIb 1g vitro infections. Antibody to the major core antigen, p24, was not detected in the vaccinated chimpanzees indicating the purity of the gp120 vaccine preparation. HTLV—IIIb viral stocks have been prepared and titered 1p vitro and, after 19 yiyg infectivity titration in chimpanzees, will be used to challenge the vaccinated animals. If the vaccin- ated animals can resist challenge with the homologous virus, challenge with a heterologous virus will be evaluated. Research sponsored, at least in part, by the National Cancer Institute, DHHS, under Contract Number NOl-CO-23910 with Program Resources, Inc. FRIDAY, JUNE 5 Prevention/Public Health—Monitoring Changes in Sexual Behavior Self-Reported Behavioral Change in Homosexual Men in the San F.8.1 Francisco City Clinic Cohort LYNDA S. DOLL*, W. DARROW*, P. O'MALLEY**, T. BODECKER**, H. JAFFE*; *AIDS Program, Center for Infectious Diseases, CDC, Atlanta, GA, **San Francisco Department of Public Health, San Francisco, CA. Although studies have documented recent declines in high-risk sexual behaviors in homosexual men, none have used information collected before the AIDS epidemic as a baseline for assessing behavioral change. of 125 men who answered questions regarding their sexual practices in 1978, 1984, and 1985, 90% had reduced their number of nonsteady partners between 1978 and 1985. The number of nonsteady partners decreased from a median of 16 in the previous 4 months in 1978 to 1 in 1985. Comparison of men who decreased their number of nonsteady partners between 1978 and 1984 with those who did not showed no demographic differences between the groups. Exposure risk from insertive and receptive anogenital and orogenital contact declined significantly between 1978 and 1984, although anogenital contact failed to decline further in 1985. Overall decline for orogenital contacts, while significant, was not as dramatic. Comparison of long-term negatives (522 of sample) with men who seroconverted between 1978 and 1984 (41% of sample) showed that seroconvertors were younger (mean=28 years) than long-term negatives (mean=33 years). Both groups significantly decreased their number of nonsteady partners and their participation in high-risk sexual practices. The groups did not differ in their decrease in these activities over the 7-year period. While these dramatic declines provide an indirect and positive evaluation of risk- reduction educational programming, in 1985, some men continued to engage in high-risk behaviors. These data emphasize the need to characterize men who have and have not changed their behavior in response to the AIDS epidemic. F 8.2 Prevention of HIV Infection Among Gay and Bisexual Men: Two Longitudinal Studies. Co-Authors: L. MCKUSICK, THOMAS J. COATES, J.A. WILEY, S.F. MORIN, R. STALL, University of California, San Francisco, School of Medicine. This presentation will focus on levels of high risk sexual behavior and predictors of compliance to safe sex guidelines among gay and bisexual men in San Francisco. The first cohort is a sample of 700 men recruited for participation in 1983 and 1984 as the epidemic was just beginning in San Francisco. The San Francisco Men's Health Study is a population-based sample of 843 single men from the 19 census tracts in San Francisco with the highest cumulative incidence of AIDS in 1984. They have also lowered significantly rates of participation in dangerous sexual activity. As of May, 1985, approximately 25% of the cohort were still engaged in at least one high risk sexual act per month which involved sex outside of a primary relationship. Our most recent analyses of predictors of levels of high risk sexual activity, cross-validated in both cohorts, identified 8 variables to be significantly related (R= .47, p is less than .001) to sustained low risk activity in a multiple regression analysis. Personal efficacy the belief that one is capable of making recommended changes), was most powerfully associated with level of risk activity. Men in relationships were also found to be engaged more frequently in behavior that might transmit HIV than men not in relationships. Depression was greater in those who subsequently reduced risk. Younger men were more likely to be engaged in high risk activity and level of agreement with risk reduction guidelines was related to low risk activity. Denial of the virulence of the epidemic was related to continued high risk activity. Holding a visual image of AIDS deterioration was related to low risk activity. Finally, levels of both drug and alcohol use during sexual activity was related to non-compliance with safe sex practices. F 8_3 Condom Use in a Cohort of Gay 5 Bisexual Men RONALD 0. VALDISERRI, D. LYTER, C. CALLAHAN, L. KINGSLEY, C. RINALDO, AIDS Prevention Project & Pitt Men's Study, University of Pittsburgh, Pgh-. PA Between 5/1/86 and 12/1/86 503 gay and bisexual men enrolled in a prospective study of HIV infection were surveyed concerning their attitudes and use of con- doms. 328 (65%) reported at least one episode of anal intercourse during the 6 months prior to the survey and constitute the study population. Most men were non—unnogamous with 72% reporting 2-100 sexual partners in the last 6 months. 242 reported half or more of their sexual partners were anonymous. Although a majority (90%) endorsed the belief that condoms can "reduce the spread of AIDS," 62% stated that they "never" or "hardly ever" wore a condom during anal inter- course in the last 6 months and 64% stated that their partners "never" or "hard— ly ever" were condoms during anal intercourse. 8% of the men reported a past experience of condom breakage but the majority indicated this happened only once. 5% reported a past experience of condom slippage, usually before ejacu- lation; but again most (602) related that this was rare or happened only once. Factors involved in the underutilization of condoms in this population may re- late to the following surveyed perceptions: condoms spoil sex (22%); purchas- ing condoms is embarrassing (18%); using condoms "turns off" partners (16%); condoms are not readily available (22%); or condoms are only used by "straights" (26%). Their underutilization is probably not related to deficits in knowledge since 91% identified receptive anal intercourse as the highest risk sexual ac- tivity vis-a—vis AIDS transmission. Also, the fact that 35% reported that they were "high" on alcohol/drugs with half or more of their partners may contribute to this underutilization. Finally, this underutilization may relate to the re- latively low incidence of AIDS in Pittsburgh, and the fact that 60% of our group did not personally know someone with AIDS. 213 F 8_4 Changes in Sexual Activities Among Participants in the Multicenter AIDS Cohort Study ROBIN 595, D. Ostrow, R. Valdlsseri, M. Van Raden, B. Visscher, B.F. Polk, for the Multicenter AIDS Cohort Study, NIH, Bethesda, MD 4,955 gay/bisexual men were enrolled in a prospective study of the natural history of HIV infection. Data on self—reported sexual activities were collected at four 6-month intervals beginning in April, 1984. We observed a study increase in celibacy (2% - 12%) and monogamy (12% 4 27%) and a decrease in number of partners. In general, there was a reduction in all high risk behaviors; the proportion not practicing receptive anal intercourse increased from 26% to 49%. Fisting was uncommon at baseline and has become a rare prac- tice. Use of douches/enemas has declined markedly. At baseline, 66% of MACS participants reported use of nitrite inhalants; this proportion had declined to 44% at the fourth visit. The use of condoms with anal sex (either receptive on insertive) doubled over the course of 4 visits, but still less than one—third reported using con— doms with anal sex. The direction and magnitude of reported changes in activi— ties varied modestly when stratified by race, age, city, education or HIV antibody status. We do not now have data to determine whether our participants are becoming more selective in choosing partners who have similar serologic status. We will present information on behavior changes through five visits. These data demonstrate a marked and continued decrease in sexual practices that increase risk of HIV infection. However, further reductions are clearly warranted. Safe sex education programs must be improved, expanded and sustained. F 8 5 Declining incidence of sexually transmitted diseases as a result of ' ' an AIDS—prevention campaign. B.D.P. EIJROND*, J.A.R. VAN DEN HOEK**, J.A. EMSBROEK**, F. JANSEN SCHOONHOVEN **, R.A. COUTINHO**; * AIDS policy co—ordination of the Netherlands; ** Muni— cipal Health Service Amsterdam. An AIDS—prevention campaign especially directed towards homosexual men started in the Netherlands in 1983. This campaign was nationwide but a special effort was made in Amsterdam. To see what influence this campaign had on the lifestyle of homosexual men, we studied rectal (RG) and homosexually acquired (HAG) male cases of gonorrhoea treated at the STD-clinics of the Municipal Health Service: year 1981 1982 1983 1984 1985 male cases total 3,407 3,139 2,837 2,380 2,051 of RC (Z) 451 (13.2) 502 (16.0) 471 (16.6) 271(11.4) 218 (10.6) gonorrhoea HAG (Z) 1,060(31.1) 1,137(36.2) 1,013(35.7) 570(23.9) 435 (21.2) The incidence of syphilis among men in Amsterdam was in 1981 108, in 1982 110, in 1983 101, in 1984 91,5 and in 1985 53 per 100,000. From these data we conclude that homosexual men in Amsterdam changed their sexual lifestyle since 1984. Data from 1986 will be presented at the conference. F_8.6 Use of an AIDS HolHne as an Educafional Toolas we“ as a Measure of Effectiveness of Outreach Efforts. INDIRA KOTVAL. B.M. Bronson, T. Widmark. W. Hansen-Sparks. Health Edu- cation Resource Organization. Baltimore. MD. USA HERO has conducted an AIDS information and referral hotline since 1983. A record of each ca" was kept, and analysed to Idenfify trends. to characterue the different types of caller. and to categorize the type of information asked or advice sought. This analysis demonstrated that the hotline was primarily an information tool. rather than a crifls or counsefing service. In order of frequency, caHers were gay white males (33.7%), straightwhite females (28.3%]. gay black males (10.5%) and straight black females (8.5%). The majority of calls (53.3%) were for gen- eral information on AIDS; “0.3% of calls were for referrals to antibody testing shes. 8.1% asked symptoms of AIDS. and only 2.1% of caHers were seeking counsefing. Analysis of calls after subsequent targeted outreach efforts by HERO to specific groups (minorities, IV drug usersl indicated an increase of calls from these groups. Tins suggests that tracking of hotnne caHs can be used to help evaluate the effectiveness of outreach efforts. FRIDAY, JUNE 5 Immunology—Viral Replication F 9 1 Mononuclear Phagocytes and Accessory Cells in the Pathogenesis ' ' of AIDS MIKULAS POPOVIC, S. GARTNER AND R.C. GALLO, Laboratory of Tumor Cell Biology, NCI/NIH, Bethesda, MD. Several lines of evidence indicate that, 33 vivo, cells other than T4+ lymphocytes harbor HTLV-III/LAV. Using a number of different methods, extensive studies of brain, lung, lymph node and skin tissues from HTLV- III/LAV-positive individuals clearly established that the virus-positive cells belong to the mononuclear phagocyte lineage. In brain tissue the virus—positive cells exhibited characteristics of monocyte/macrophages, in the lung they were mainly alveolar macrophages, in the lymph nodes they were the follicular dendritic cells and, in the epidermis, the Langerhans cells were HTLv-III/LAV positive. In vitro virological studies using monocyte/macrophages as targets demohstrated that these cells are highly susceptible to and permissive for the virus, particularly those isolates which were recovered from cells of the mononuclear phagocyte lineage. The longevity of virus production, the cytopathic effect and the presence of infectious virus particles within vacuoles indicates that these types of cells represent not only targets for HTLV-III/LAV, but perhaps more importantly, they are the primary source of virus persistence lfl vivo. Moreover, the normal physiological role of mononuclear phagocytes strongly suggests that these virus—infected cells are responsible for virus dissemination. The biological properties as well as the nucleic acid analysis of several isolates recovered from various types of cells from the mononuclear phagocyte lineage will be discussed. F 9_2 Cytokine Infected THOMAS M. FOLKS*, J. JUSTEMENT*, K. CLOUSE***, C.A. DINARELLO**, M. DUKOVITCH, I.S. FAUCI*, et al., *National Institutes of Health, Bethesda, MD, **Tufts University, Boston, MA, ***Georgetown Univ., Washington, D.C. Cells of the monocyte/macrophage lineage have been implicated as major targets of HIV infection. In order to further study this phenomenon, the promonocyte cell line, U937, has been used as a model for monocyte infection. Following HIV infection of U937 cells, chronic low-level virus-producing clones can be isolated which do not manifest a cytopathic effect and which contain integrated HIV proviral DNA copies. Clones such as these permit the detailed study of factors which might regulate or influence HIV expression. Our findings have shown that T cell and monocyte derived factors can control virus expression in these chronic HIV-producing clones. The T cell lymphokine, granulocyte-macrophage colony stimulating factor, can increase HIV production in one clone, U1, by 3 to 4 fold. Another lymphokine, ganma interferon, produces the opposite effect by inhibiting virus production. Monokines derived from LPS induced macrophages were shown to strongly up-regulate HIV production in these clones. The purified monokine, IL-ls, has been tested for viral regulatory properties in U1. Even though recombinant IL-ls had no effect on HIV expression, antibody to IL-1B inhibited the enhanced expression of HIV in U1 by other factors. Interestingly, following factor induction IL-16 mRNA was up-regulated 20 fold in U] over uninfected U937 cells. This implies a regulatory role for IL-IB in controlling HIV expression in this chronic HIV-producing clone and suggests that the inductive signals for virus expression by other external factors involve IL-1B in the final common pathway. Regulated Control of HIV Expression in Chronically Promonocyte Clones F 9 3 Quantitative Cytofluorographic Analysis of HIV Infected ' ' Macrophages (Me): Removal of CD4 Positive Lymphocytes Through a Cell Fusion Process SUZANNE CROHE. JOHN MILLS, MICHAEL S. of Med.. San Francisco. CA 94110 It is unlikely that HIV infection of CD4 lymphocytes alone can fully explain the immune dysfunction observed in AIDS. Me in- fected with HIV may directly cause AIDS by serving as a virus reservoir and by removing 004 T lymphocytes through an HIV enve- lope glycoprotein mediated fusion process. Quantitation of cell surface and cytoplasmic antigen in infected cells has been diffi— cult uaing conventional innunofluoreacent staining of cells on slides. We have developed a system which permits maintenance and differentiation of human peripheral blood monocytes in suspension culture for prolonged periods of time. This allows quantitation of CD4 and/or HIV antigens on single infected and uninfected us by two color immunotTfiorescent cytotluorographic analysis. These studies have shown: (1) CD4 antigen is present on monocytes, antigen expression showing marked donor variability (28—85% of cells). (2) Both 0KT4 and 0KT4a epitopes are present at equiva— lent levels on Me. (3) CD4 antigen density increases tenfold dur- ing the first 1—2 weeks of culture. (4) Cultured M9 between 2 hours and 57 days of age can be infected with HIV. (5) HIV p24 antigen is present in up to 70x of infected cells. (6) HIV in- fected M9 frequently form nultinucleated giant cells with poor ad- herence characteristics. (7) Two color immunofluorescent labeling shown HIV infected H0 fuse and remove CD4 lymphocytes in vitro. MCGRATH, UCSF & SFGH, Dept. with 214 F.“ \II'I‘ElEJgTIgIVl”: MINI BONE "ARR“ CELLS BY THE HIM" IHIJHODEFICIENCY v. LUNARDI-ISEANDAR", M.T. NUggRE“, v. EEORGOULIAS*. F. BARRE-SINOUSSIH. CLAUDE JASMIN , J.C. CHERMANN et al., INSERM U268, Hop. Paul Brousse. B.P. 200, 94804 Villejuif Cédex, France and **Department of Virology, Institut Pasteur, 25, rue du Dr. Roux, 75015 PARIS, France. In order to examine whether immature T cell precursors are infectable by HIV, normal bone marrow cells were infected in vitro, before and after deple- tion of mature T cells with 0KT3 or T11 plus complement. The culture was performed in the presence of phytohemagglutinin (PHA) and recombinant 1L2 (rILZ). Five to 10% of unfractionated or T-cell depleted bone marrow cells were specifically labelled with a fluorescein-conjugated HIV preparation. The peak of reverse transcriptase activity was detected at day 15 in all cases. At this time, infected cultures of T-cell depleted bone marrow were composed of T3+(50-55%), T8+(50-55%) but not T4+ (less than 2%) cells whereas non-infected cultures were composed of T3+(70-78%), T8+(15-20%) and T4+(50-55%) cells. Non—infected bone marrow cells generated a relatively high number of T-cell colonies in methylcellulose (more than 100 colonies/5x104 cells at day 15) whereas for infected cells. both unfractionated and cell fractions, displayed a time-dependent impaired T-cell colony growth capacity (less than 20 colonies/5x104 cells). Phenotypic characterization of T-cell colonies obtained from infected bone marrow cells revealed the presence of T3+,T4+,T6+,T8+ cells whereas colonies derived from non-infected cells were composed of T3+,T4+ and T3+, T8+ but not T6+ cells. This model thus seems to mimic the abnormal proliferation and differentiation of T-CFC observed in patients with AIDS and Persistent Lymphadenopathy Syn- drome. Low Numbers of Cytotoxic/Suppressor CD8+ Lymphocytes Prevent HIV Replication in Autologous Purified CD4+ Lymphocytes F.9.5 CHRISTOPHER M. WALKER, D.J. MOODY, D.P. STITES. and J.A. LEVY, Cancer Research Institute and Department of Laboratory Medicine, University of California, School of Medicine, San Francisco, CA. Our studies have focused on the role of cytotoxic/suppressor T lymphocytes in the control of human immunodeficiency virus (HIV) replication in cultures of peripheral blood mononuclear cells (PMC) from HIV seropositive subjects. Prev- iously published results demonstrated that when this T cell subset, which ex- presses the CD8 (0KT8/Leu2) surface antigen, is removed from PMC by cellular immunoaffinity chromatography and anti-CD8 antibodies, HIV replication is detected. Reconstitution of these cultures with the recovered CD8+cells abro- gated HIV replication. Some individuals have been identified whose PMC fail to release HIV even after CD8+ cell depletion. Analysis of this cell population revealed that it con- tained 10-152 contaminating CD8+ cells. To determine if these cells were suf— ficient to interfere with HIV replication in the PMC, we specifically enriched for CD4+ cells using anti-CD4 antibodies. The resulting population, which contained greater than 902 CD4+ and less than 51 CD8+ cells, routinely yielded high titers of HIV. while PMC depleted of CD8+ cells by negative sel- ection as described above did not produce virus. Readdition of CD8+ cells inhibited replication of HIV, and prevented the appearance of HIV-induced cyto- pathology which was often evident in cultures of purified CD4+ cells. These results suggest that most HIV seropositive individuals harbour HIV in their peripheral blood CD4+ cells, and that the efficiency of CD8+ cell con- trol of HIV replication within this subset varies from individual to individual. F.g.6 Immunologic Profiles of Mothers in Perinatal Transmission of HIV Infection HENRY FRANCIS M.D.*,N. LUBAKI‘, M.P.DUMA*, RN RYDER*,J MANN***, T.C. QUINN**, et 31., * Project SIDA, Kinshasa, Zaire,**NIAID, Johns Hopkins Univ,*** "H0 Geneva, Switerland. HIV infection is known to infect T—helper lymphocytes and many other cells important to the function of the cellular immune system. To assess if these effects are associated with perinatal transmission of HIV, we used a fluorescent automatic cell counter to evaluate the levels of Leu 2,3,4,7,11,2H4 and 434 positive lymphocytes in HIV seropositive mothers who gave birth to lg“ western blot positive infants, HIV seropositive mothers of HIV IgM seronegative children and seronegative control mothers who were matched for age and parity. of the 234 mothers who delivered babies in the study group in Kinshasa, Zaire, 25 were HIV seropositive. Six of the 25 mothers had HIV IgM seropostive infants. The mothers of the IgM positive babies had a significantly lower» T-helper/T—suppressor ratio (.57:.lZ) than the mothersof 13“ negative babies (3.3: .65) p<.001. The mothers of IgM positive children also had significantly more T-suppressors (8201257 cell/mm3) than mothers of IgM negative babies (375258 cells/mm3) but no differences in Leu3+2H4+ or Leu3+4B4+ cells. HIV positive mothers of IgM negative infants and seronegative control motherrhad similar T-helpet,T-suppressor,2H4 and 434 population, but the HIV positive women had sighficantly lower numbers of Leu 11+ (NK) cells (3325 cells/mm3 vs 130214 cells/mm3) p<.001. HIV positive motherswho transmit AIDS to their children have inversed T-helper/T-suppressor ratio and elevated. suppressor cells which are signficantly different from what is seen in HIV positive mothers who do not transmit the infection to their infants. with further study, these lym hocyte parameters may be used to judge the risk of perinatally transmitted IV infection. Closing Plenary Session F.10 Chairmen: Jean-Claude Gluckman Chalrman, I! International Conference on AIDS Paris, France Lars Olaf Kallinge Chalrman, IV International Conference on AIDS Stockholm, Sweden Summary and Current Status of AIDS Research June Osborn, Dean, School of Public Health, University of Michigan, Ann Arbor, Michigan. Lars Olaf Kslllngs, Director, Notion-l Bacteriological Laboratories, Stockholm, Sweden. Edward H. Brandt, Jr., Chancellor, University of Maryland, Baltimore, Maryland. Introduction of the Secretary Robert E. Vindom, Assistant Secretary for Health, U.S. Department of Health and Human Services, Washington, D.C. Concluding Address: AIDS —— Charge for the Future The Honorable Otis R. Bowen, Secretary, U.S. Department of Health and Human Services, Washington, D.C. 215 FRIDAY, JUNE 5 _A... Abdul-Quader, A, MR201 (43); THP.178 (I93) Abel, C, WP.10 (112) Ablashi, D, MP.146 (34); TP.20 (65); THP.3 (I64) Abrams, D, M.11.2 (9); M.11.3 (9); TP.44 (69); TP.197 (95); WP.47 (118); WP.58 (120); WP.207 (144); THP.57 (173) Abrams, E, WP.62 (120); TH.11.3 (162) Achterhof, L, TP.193 (94); THP.191 (195) Acra, J, TP.187 (93) Acuna, G, TP.184 (93) Adachi, A, E74 (212) Adachi, N, WP.209 (145) Adams, L, WP.40 (117); WP.133 (132) Adelsberg, B, WP.145 (134) Ades, A, MR47 (18) Adler, W, WP.119 (130); WP.123 (130) Adrien, A, TP.175 (91) Ahearne, P, M.10.3 (8); TP.128 (83) Ahlgren, D, WP.9O (125) Aime, F, M.5.4 (4) Aiuti, F, TP.117 (82) Aizawa, H, MP.235 (49) Ajdukovic, D, MP.102 (27) Albert, J, MR11 (12); THP.13 (165); THP.29 (168) Albrecht, P, TP.245 (103) Alcami, J, THP.116 (182) Alderette, B, E4.5 (209) Alderman, M, TH.11.2 (161); THP41 (170) Alessi, E, TP.164 (89); WP.161 (137) Alexander, S, MESS (24); MP.95 (26); TP.242 (102); WP.226 (148); THP.71 (175); THP.245 (204) Alger, L, MP.85 (24) Alizon, M, TH.2.1 (153) Allain, J, MR45 (17); MR87 (24); MP.ll9 (30); T81 (58); TP.38 (68); TP.69 (74); THP.9 (165); E22 (207) Allaire, J, MP80 (23) Allan, J, MR29 (15); TP.7 (63); WP.17 (113) Allegra, C, TH.4.1 (155) Allen, J, M.3.5 (2); MP.l69 (38); TP.133 (84); WP.130 (I32); THP.102 (180) Allen, R, WP.242 (150) Allen, S, ”[101 (60) Allouche, M, MP.112 (28) Alter, H, TP.74 (74); WP.107 (128); WP.249 (151) Alter, M, W45 (117); TH.5.3 (156) Amadori, A, MP.153 (35); TP.104 (79) Ambinder, R, MP.10 (11) Amiel, C, MP.118 (29) Amitai, H, T.5.1 (55); WP.148 (135); H, THP.153 (189) Amoroso, W, M.6.2 (4) Anand, R, TP.36 (68); WP.29 (115); THP.228 (201 ); THP.233 (202) Ancelle, R, WP.87 (124); THP.74 (175); THP81 (177) Anderson, D, M.11.6 (9); MP.Z7 (14); WP.168 (138); E72 (212) Anderson, M, MP.141 (33); WP.131 (132); THP.237 (203) Anderson, R, M.3.2 (1); TP.184 (93); THP.221 (200) Anderson, V, WP.170 (138) Andiman, W, TP.150 (87) Andrade, D, E61 (211) Andreev, S, MP97 (26) Andrews, C, M.11.4 (9); TP.144 (86) Andrews, L, THP.220 (200) Andreyev, S, WP.98 (126) Andrieu, J, THP.239 (203) Andriolo, M, E3.5 (208) Andron, L, MP.140 (33) Andrulis, D, WP.211 (145) Andzhaparidze, O, THP.40 (170) Angeloni, P, WP.122 (130); WP.248 (151) Anns, M, WP.188 (141) Anselmo, M, WP.134 (132) Antonen, J, M.10.4 (8); MP.119 (30) Antony, M, E3.4 (208) Antunes, E, MP.42 (17) Antunes, F, THP.88 (178) Aoussi, E, TP.165 (90) Appleman, M, T72 (57); WP.156 (136); THP.149 (188) Aquilante, R, WP.152 (135) Arakaki, D, TH.4.1 (155) Archer, G, WP.243 (150) Archibald, D, WP.84 (124) Arcidiacono, I, WP.250 (152) Arendrup, M, TP.81 (76) Argelagues, E, MP.165 (37) Arnaiz-Villena, A, THP.116 (182) Arnow, P, TR212 (97) Aronstam, A, MP.54 (19) Arrizabalaga, J, TP. 118 (82) Arthur, L, M102 (8); TP.10 (64); TP.13 (64); WP.3 (110); TH.2.5 (154); E7.6 (212) Arya, S, MP.25 (I4); TH.2.3 (153); THP.15 (166); THP.23 (I67) Asher, D, TP.29 (67); WP.3 (110) Ashley, R, E1.6 (206) Ashman, M, THP.240 (203) Asjo, B, MP.11 (12); THP.13 (165); THP.238 (203) Assogba, U, WP.87 (124) Atherton, S, MR146 (34) Atkinson, J, MP.145 (34); MP.200 (43) Atkinson, W, MR184 (40) Aubry, J, WP.126 (131) Autran, B, MP.123 (30); MP.149 (35); WP.126 (131); WP.216 (146); THP.76 (176) Avrunin, J, TP.174 (91 ); WP.172 (I39) Axel, R, M.4.3 (3); WP.2 (110) Axthelm, M, WP.34 (116) Ayehunie, S, MR214 (45) _B_ Baba, M, MP4 (10); T.4.2 (54); TPl (62) Bacchetti, P, TP.53 (71); THP.43 (I70); F.1.5 (206) Bach, M, MP.10 (11) Bacheler, L, TP.35 (68); Wp.28 (115); THP.27 (168) 217 Bachi, T, THP.14 (165) Badamchian, M, THP.107 (181) Badner, V, THP.213 (199) Baffoni, L, TP.112 (81) Bailey, S, TP.154 (88) Bailey, V, MP.l91 (42); TP.184 (93); WP.175 (139) Baillou, A, WP.27 (114) Bain, B, T48 (70) Baird, B, WP.205 (144); THP.219 (200) Baird, K, WP.168 (138) Baker, J, TH.3.6 (155) Baker, L, THP.243 (204) Baker, S, MP.86 (24) Balfour, Jr., H, TP.231 (101) Balzarini, J, MP.4 (10); T.4.2 (54); TR] (62) Bandemer, C, MP.188 (41) Barbaro, D, THP.229 (201) Barbier, M, MP.80 (23) Barin, F, TP.7 (63); WP.27 (114); E25 (207); E6.2 (211); E6.3 (211); E6.6 (211) Baringtang, D, TH.4.2 (155) Barlow, J, TH.4.2 (155) Barnes, S, THP.179 (193) Barnes, T, MP.63 (20) Barnett, J, TH.8.5 (159) Barnhart, J, T49 (70); TP.51 (71); W46 (118) Baroldi, G, THP.165 (191) Baron, G, WP.105 (127); THR240 (203) Barr, D, E5.3 (210) Barre-Sinoussi, F, MR37 (16); WP.37 (116); WP.77 (123); THP.37 (169); E21 (207); E4.6 (209); E9.4 (214); Barrera, J, MP.165 (37) Barry, A, MP89 (25); WP.210 (145) Barry, M, TP.47 (70) Bartczak, S, mPlél (190) Bartelme, S, MP201 (43); WP.72 (122); THP.178 (193) Bartholomew, C, TP.96 (78); E6.4 (211) Bartlett, E, MR188 (41) Bartnof, H, MR194 (42); TP.203 (96); WP.193 (I42); THP.218 (I99); THP.224 (200) Baruchel, S, MP.117 (29) Basiripour, L, M.4.6 (3) Baskin, G, WP.19 (113); THP.21 (167); THP.30 (168); THP.113 (182) Bassett, M, M.8.3 (6) Basten, A, MP.168 (38) Bates, J, WP.69 (121) Baum, B, MR152 (35) Baum, G, TP.168 (90) Bausell, B, TP.172 (91 ) Baxter, R, MR210 (45 ) Bayende, E, TH.7.6 (158) Bayer, R, E51 (210) Beall, G, THP.160 (190) Beasley, P, E1.5 (206) Beaton, D, MP.59 (20) Beatrice, S, TP.69 (74) Beatson, D, TP.124 (83); TP.238 ([02) Beaver, B, THP.15 (I66); THP.23 (167) Beavers, B, MR25 (14) Bebenroth, D, WP.141 (133); THP.103 (180) INDEX Becherer, P, MR78 (23) Bechtel, G, TP.202 (96) Becker, J, MR37 (16) Beckham, D, MP.197 (43) Beckstead, J, TP.115 (81) Bedarida, G, WP.250 (152) Bednarik, D, WP.38 (116) Bedos, J, MP.158 (36) Beers, V, WP.211 (145) Beeson, D, THP.207 (198) Behets, F, TH.7.6 (158) Beil, J, TP.57 (72) Bekesi, G, WP.115 (129) Bekesi, J, MP.132 (32); TP.131 (84); WP.114 (129); THP.117 (183) Bellanti, J, MP.18 (13) Bellin, E, TP150 (87) Bellobuono, A, MR249 (51) Bellonti, J, MP.188 (41) Belloso, L, TP.118 (82) Belman, A, TP.146 (86); W53 (109) Belongia, E, MP.182 (40) Bender, B, WP.123 (130) Bene, M, MP.118 (29) Benjers, B, THP.12 (165) Bensch, K, MP.12 (12) Benson, C, TP.225 (100) Benter, T, M.9.6 (7) Bentley, J, WP.211 (145) Benveniste, R, MP.13 (12); MP.15 (12); THP.30 (I68) Berardi, V, THP.175 (192) Beresford, H, WP.159 (136) Beresford, R, WP.158 (136) Beretta, A, WP.124 (131) Berg, G, WP.223 (147) Berg, K, WP.229 (148) Berg, S, TP.135 (85); TP.156 (88) Bergdahl, S, THP.13 (165); THP.238 (203) Berger, J, MP.139 (33); MP.143 (34); T.8.3 (58); TP.136 (85); THP.155 (189) Berggren, I, THP.78 (176) Bergman, T, MR39 (16) Berlin, F, MP.198 (43) Berman, M, TP.11 (64); TP.119 (82) Berman, P, M.4.4 (3); WP.25 (114); WP.107 (128); THP.20 (166); THP.125 (184) Bernard, J, T.16.5 (62) Bernstein, D, TP.116 (81 ) Bernstein, L, F.3.4 (208) Bemstein-Singer, M, THP.144 (187) Berry, A, TP.208 (97) Berry, C, T.10.5 (60) Berry, G, WP.86 (124) Berthaud, M, THP.209 (198) Berti, E, WP.161 (137) Bertram, J, MP231 (48) Bertrand, W, T.7.6 (57) Bess, J, TP.10 (64); TP.13 (64); E16 (212) Beth-Giraldo, E, TP.244 (103) Bettinger, C, THP.186 (194) Beverley, P, TP.4 (63); TH.9.4 (160); TH.9.6 (160) Bhan, A, TP.129 (84) Bianchi, F, TP.112 (81) Bianco, C, TP.240 (102); WP.236 (149); THP.208 (198); THP.243 (204) Biberfeld, G, M.10.6 (8); M293 (25); T1286 (76); WP.128 (131); THP.78 (176); THP.238 (203) Biberfeld, P, TP.125 (83); WP.5 (111); WP.128 (131) Biel, J, WP.88 (125) Bierling, P, WP.228 (148); THP.170 (191) Biemacki, P, TP.176 (91); WP.197 (143) Biesert, L, WP.24 (114) Biggar, R, MR65 (21); TR28 (67); TP.56 (71); W26 (106); WP.68 (121) Bigger, B, THP.71 (175) Biglieri, E, TP.197 (95); WP.207 (144) Bihari, B, WP.227 (148); THP.124 (184) Bilello, J, THP.12 (165) Bircher, J, THP.77 (176) Birriel, J, THP.167 (191) Birx, D, WP.110 (128); THP.105 (181) Bishburg, E, MP.160 (36); E, TP.57 (72) Bishop, P, THP.129 (185) Bisset, C, THP.172 (192) Black, I, WP.180 (140) Black, P, WP.198 (143) Blackwelder, W, WP.67 (121 ); THP.64 (174) Blain, N, WP.8 (111) Blanche, S, TH.7.4 (158) Blasco, E, TP.118 (82) Blattner, W, T33 (53); T48 (70); E12 (206); F.4.3 (209); E6.4 (211); F65 (211) Bloch, A, TP.42 (69); THP.86 (177) Bloom, J, TH.11.2 (161) Blough, H, TP.23 (66) Blumberg, R, WP.104 (127) Blumenfeld, W, THP.163 (190) Bocoon-Gibod, L, MP.117 (29) Bockelman, M, WP.22 (114) Bodecker, T, F.8.1 (213) Bodner, A, TP.242 (102); WP.21 (113); WP.128 (131); THP.245 (204) Bofill, M, WP.137 (133) Bogaerts, M, THP.227 (201) Bogner, J, WP.165 (137) Bohan, C, MR26 (14) Boix, J, TP.167 (90) Bolan, G, TP.51 (71) Boland, M, MP.162 (37); MP213 (45); TP.215 (98); WP.213 (145); THP.212 (198) Bolgiano, D, WP.49 (118) Bolognesi, D, T.16.4 (62); T.9.4 (59); TP.128 (83); TP.132 (84); F.7.6 (212) Bolton, W, WP.243 (150) Bonapour, B, TP.114 (81 ) Bonavida, B, TP.127 (83); WP.103 (127) Bond, G, TP.194 (94) Bond, W, MR229 (48); WP.233 (149) Bonhomme, M, T.6.3 (56) Bonk, S, THP.145 (187) Bonner, R, TP.245 (103) Bonneux, L, MP.82 (23); W24 (106) Bonney, D, WP.179 (140) Boo, T, MP.74 (22) Boone, D, WP.245 (151); THP.129 (185) Borek, E, WP.55 (119) Borkowsky, W, W.5.2 (108); WP.141 (133); THP.103 (180); THP.145 (187) Borucki, M, TP.159 (89) Bosch, D, MP.237 (49) 218 Bosio, R, WP.95 (126) Bosire, M, TH.5.5 (157) Boswell, R, T.7.2 (57); WP.107 (128); WP.156 (136) Bosworth, C, WP.113 (129); THP.114 (182) Bottiger, B, M.10.6 (8); WP.83 (124); THP.29 (168); THP.78 (176) Bottiger, M, M.6.5 (5) Bouhasin, J, THP.127 (184) Boulos, C, THP.63 (174) Boulos, R, THP.63 (174) Bouramoue, C, WP.79 (123) Bourguignon, L, WP.105 (127) Bouscary, D, THP.123 (184) Boussin, F, TP.27 (67) Bouvet, E, TP.180 (92) Bowles, C, TP.210 (97) Bowman, R, MP250 (51 ); WP.235 (149) Bowry, T, TP.41 (69); TP.249 (104) Boyd, V, THP.34 (169) Boyer, C, THP.190 (195) Boyer, R, THP.193 (195) Boyko, W, M.3.3 (2); M.6.3 (5); MP.111 (28); TP.99 (79) Boyle, R, MR43 (17) Boylen, C, THP.151 (188) Boynes, F, THP.179 (193) Bracco, M, MP.134 (32) Brackmann, H, TH.10.4 (161); THP.168 (191) Braddick, M, WP.50 (118); TH.7.5 (158) Brahic, M, MP2 (10) Brandes, T, THP.221 (200) Brandt, L, F34 (208) Branson, B, MP.181 (40); TP.191 (94); WP.185 (141); THP.184 (194); F.8.6 (213) Brasfield, T, MP.174 (39) Bratt, G, MP93 (25); THP.130 (185) Braun, B, MP.244 (50); T2235 (101) Braun, D, THP.101 (180) Braun, M, WP.74 (122); TH.2.5 (154) Braun, N, THP.231 (202) Braunstein, L, THP.214 (199) Bredberg-Raden, U, TP.86 ( 76); THP.29 (168) Brede, H, WP.24 (114) Breer, P, MP.181 (40) Brenner, M, W.5.4 (109) Brettle, R, MP.137 (33); TP.205 (96); WP.204 (I44); THP.172 (192) Brettler, D, M.11.4 (9); MP.86 (24); MP.240 (50); TP.144 (86) Brew, B, WP.149 (135 ) Brewster, F, M.11.4 (9); TP.144 (86) Brewton, G, TP.134 (84); TP.218 (98); THP.135 (186); THP.236 (202) Brey, R, MP.115 (29); WP.156 (136) Bricaire, F, WP.138 (133); THP.141 (187) Bridge, P, M.5.3 (4) Brink, B, M.8.2 (6) Brisker, J, WP.152 (135) Britton, S, MP214 (45) Britz, J, MP.107 (28) Broaddus, R, WP.74 (122); THP.70 (175) Brockmeyer, N, THP.131 (185) Broder, S, T.2.3 (52); T.4.1 (54); T.4.4 (54); TP.1 (62); WP.223 (147); THP.10 (165) Brodie, B, MR206 (44) Brodie, H, MP.221 (47); WP.231 (148) INDEX Bron, C, THP.14 (165) Brondum, J, MP.185 (41); TP.179 (92) Brossard, Y, THP.170 (191) Brousse, N, MP2 (10) Brouwers, P, THP.146 (187) Brown, C, WP.155 (136); THP.193 (195) Brown, D, MP90 (25) Brown, G, THP.221 (200) Brown, L, MR203 (44); TH.11.6 (162) Brown, M, MP.114 (29) Brown, R, WP.139 (133) Browning, R, WP.53 (119) Brozicevic, M, THP.192 (I95) Brucker, G, TP.229 (100); THP.24 (167) Briihwiler, J, WP.81 (123) Brun-Vezinet, F, MP.148 (34); MP.189 (41); TP.27 (67); TP.37 (68); TP.153 (88); WP.32 (115); THP.24 (167); THP.33 (169); THP.75 (176); F.2.4 (207); F.6.1 (211) Brunda, M, TP.17 (65) Brundage, J, MP.81 (23); T71 (57); TP.237 (102); WP.110 (128); F.1.1 (206) Brunet, J, TP.180 (92); THP.74 (175); THP.81 (177) Brutus, J, THP.63 (174) Bubley, G, WP.224 (147) Buchner, B, TP.45 (70); TP.243 (103) Buchow, H, T.120 (82) Bucknall, A, TP.195 (95) Bucquet, D, MP.79 (23) Buimovici-Klein, E, THP.124 (181); WP.227 (148) Bfiki, B, MP21 (13) Bulkin, W, TH.11.6 (162) Buller, M, WP.100 (127) Bunin, J, MP8] (23); TP.237 (102) Buning, E, MP.183 (40) Burcham, J, MR63 (20); WP.86 (124) Burger, D, THP.128 (184) Burger, H, THP.228 (201 ); THP.233 (202) Burgess, M, THP.137 (186) Burke, D, MR81 (23); T71 (57); TP.166 (90); W35 (107); WP.17 (113); WP.110 (128); THP.99 (180); THP.105 (181); FL] (206) Burnell, R, TH.8.3 (159) Burnett, A, THP.244 (204) Burnett, W, WP.68 (121) Burns, S, THP.172 (192) Busch, K, MR152 (35) Busch, M, W.4.3 (108); W.4.5 (108); WP.237 (149) Buschman, F, WP.55 (119) Bushar, G, TP.16 (65 ) Buttner, W, TP.157 (88) Byers, R, WP.42 (117); TH.7.1 (157) Bygbjerg, I, MP.62 (20); WP.229 (148) Bykovsky, A, TP.2 (62) Byron, K, THRZ (163) _C_ Cabbad, M, WP.157 (136) Cadeo, G, MR153 (35) Cai, Q, WP.106 (127) Cain, C, THP.3 (164) Cairns, M, T.9.4 (59) Calabrese, L, TP.182 (92); THP.180 (193) Calderone, R, THP.134 (185) Calisher, C, W.2.3 (106); E83 (213) Callan, M, TH.11.5 (162) Callegari, F, MP8 (11) Calvelli, T, THP.156 (189) Calzavara, L, MP49 (18); MRSO (18) Cambie, G, WP.250 (152) Cameron, C, THP.138 (186) Cameron, D, M84 (6); MP91 (25); TH.5.5 (157) Campos, A, WP.137 (I33) Camus, F, TP.165 (90) Candido, K, WP.135 (132) Canessa, A, WP.134 (132) Cano, J, MP.165 (37);TP.167 (90) Canton, P, MR118 (29); THP.164 (I90) Cantor, K, F.6.5 (211) Cao, Y, THP.9 (165) Caouette, S, THP.128 (184) Capobianchi, M, TP.117 (82) Capon, D, M.4.5 (3); MP.19 (13); TP.31 (67) Caralis, P, WP.196 (143) Caraux, J, MP227 (48) Carcassonne, Y, T.5.6 (55) Card, R, WP.163 (137) Cardell, N, TP.59 (72) Carden, J, TP.227 (100) Carey, J, MP.105 (27) Carey, V, MR92 (25) Carleton, S, T.8.2 (58) Carlson, J, MR151 (35); MP.191 (42); TP.28 (67); TP.53 (71); WP.53 (119); THP.215 (199) Carminati, G, TP.164 (89) Carpenter, S, TH.2.6 (154) Carr, G, MP206 (44) Carron, W, THP.150 (188) Carsley, J, TP.175 (91) Cartel, J, TP.95 (78) Carter, S, M.10.2 (8); TH.2.5 (154) Carter, W, MES (11); MR216 (46) Carwein, V, T2210 (97) Casareale, D, MP108 (28); TP.103 (79) Casasnova, S, TP.187 (93) Casavant, C, TP.53 (71) Casertano, M, TR113 (81) Casey, J, F.2.6 (207) Casini, M, THP.89 (178) Cassani, F, TP.112 (81 ) Cassuto, J, T103 (60) Castagna, A, WP.89 (125) Castano, R, WP.88 (125) Castello, G, TP.244 (103) Castro, K, TP.84 (76); W.2.3 (106) Catalini, M, TP.112 (81) Catania, J, THP.185 (194) Causey, D, TP.160 (89); WP.221 (147); THP.149 (188) Cauthen, G, TP.42 (69) Cavicchini, S, WP.161 (137) Cederberg, D, WP.231 (148) Cenzuales, S, TP.230 (100) Ceparano, S, TP.244 (103) Cereb, N, MP.18 (13) Ceroni, M, THP.108 (I81) Ceuninck, D, F.6.1 (211 ) Chabner, B, TH.4.1 (155) Chace, B, TP.231 (101) Chachoua, A, TH.4.5 (156) 219 Chadburn, A, THP.230 (201) Chaisson, R, MR87 (24); T81 (58); WP.112 (129); F.1.5 (206) Chakrabarti, S, T91 (59); T.9.2 (59); W.3.1 (106); Chamaret, S, MP.80 (23); F.6.3 (211) Chamberland, M, T725 (57) Chambers, L, MP242 (50) Chan, E, MP.102 (27); WP.242 (150) Chan, H, THP.17 (166) Chan, Y, TP.90 (77) Chanas, A, THP.237 (203) Chandra, P, MP24 (14); TP.220 (99) Chandwanl, S, W.5.2 (108); WP.141 (133); THP.103 (180); THP.145 (187) Chang, K, MR95 (26) Chang, M, MP.71 (22); TP.135 (85) Chang, N, M.10.3 (8); TP.11 (64) Chang, W, TP.90 (77) Chanh, T, TP.3 (63); WP.113 (129); TH.9.5 (160); THP.102 (180); F.4.5 (209) Chanock, S, MR242 (50) Chanteau, S, TP.9S ( 78) Chapman, S, MP.223 (47) Charap, M, TH.3.3 (154) Chase, M, WP.54 (119) Chase, R, MP.147 (34) Chatziandreou, E, THP.195 (196) Cheinsong-Popov, R, T.3.4 (53) Chemtai, A, TP.41 (69) Chen, C, WP.35 (116) Chen, J, T.10.2 (60); TP.171 (91); THP.39 (170) Chen, P, THP.111 (182) Cheng-Mayer, C, WP.7 (111); WP.14 (112) Cher Mann, J, MP.149 (35 ) Cherchi, M, TP.117 (82) Chermann, J, MP.37 (16); TR53 (71 ); WP.37 (116); WP.216 (146); THP.37 (169); F.2.1 (207); F.4.6 (209); F94 (214) Cherry, N, WP.215 (146) Chesebro, B, TH.2.6 (154) Cheung, T, WP.29 (115); WP.109 (128) Chew, E, TH.8.1 (158) Chiasson, M, MR83 (24); TP.75 (75); WP.70 (122); THP.66 (174) Chieco-Bianchi, L, TP.104 (79) Chinnock, B, TP.231 (101 ) Chiodi, F, MP.ll (12); TP.132 (84); THP.29 (168) Chiuten, D, THP.234 (202) Chmiel, J, T.3.6 (53); WP.63 (120); THP.60 (173) Cho, E, THP.21 (167) Chollet-Martin, S, TP.126 (83) Chotard, J, TP.52 (71 ) Chou, D, TP.62 (72) Chou, M, WP.17 (113) Chou, T, TP.30 (67) Choutet, P, WP.27 (114) Christ, G, MP.197 (43); T.10.2 (60); TP.171 (91) Christensen, L, MP.113 (29) Christonikos, N, THP.55 (172) Chuang, M, W56 (109) Chungue, E, TP.95 ( 78) Church, J, MP.110 (28); TP.137 (85) Ciantia, F, THP.84 (177) Civeira, M, MR24 (14) Clapham, P, M.10.5 (8); T.3.4 (53); TP.3 (63) INDEX Clark, C, TP.183 (93); WP.195 (142); THP.173 (192) Clark, E, MP.15 (12) Clark, J, MP.212 (45) Clark, S, TP.122 (82) Clark, V, WP.64 (121) Clause, K, THP.53 (172) Clausen, L, M.8.2 (6) Clauvel, J, MP.148 (34); TP.216 (98); WP.228 (148); THP.170 (191) Clavel, F, TH.2.1 (153) Clayton, A, THP.72 (175) Clayton, W, MP.140 (33) Cleghom, F, TP.96 (78); F.6.4 (211) Cleland, J, MP.204 (44) Clement, M, TH.3.1 (154); THP.154 (189) Clement, T, THP.245 (204); TP.242 (102) Clements, M, WP.116 (129) Clivio, A, WP.124 (131) Clotet, B, MP.165 (37); TP.167 (90) Clouse, K, M.9.4 (7); MP.22 (13); F92 (214) Clumeck, N, TP.82 (76); WP.59 (120); WP.80 (123); THP.61 (173) Coates, R, MP.49 (18); MPSO (18); TH.4.3 (155) Coates, T, T.10.1 (60); WP.184 (141); WP.186 (141); WP.232 (149); THP.185 (194); F.8.2 (213) Cobb, E, WP.231 (148) Cochi, S, WP.122 (130) Cochran, M, MP.16 (12); W.3.4 (107) Cochran, S, MP.202 (43) Cockerill, F, MP.147 (34) Cogniaux, J, MP.124 (30); TP.23 (66) Cohen, B, MP.142 (33) Cohen, H, TP.146 (86); WP.72 (122) Cohen, J, T.4.4 (54); “12.1 (105); WP.57 (119); WP.126 (131); WP.208 (145); TH.3.1 (154); THP.151 (188) Cohen, W, WP.147 (134) Cohn, D, TP.70 (74); TP.71 (74); TP.239 (102); WP.182 (140); THP.58 (I73) Cohn, J, WP.147 (I34) Cohn, M, TP.141 (86) Cohn, S, WP.116 (129); THP.119 (183) Cole, C, THP.86 (177) Cole, P, WP.196 (143) Colebunders, R, M.8.5 (6); T.7.6 (57); TP.139 (85); TP.145 (86); W.4.6 (108); WP.136 (133); THP.139 (186) Collalti, E, MR33 (15) Collier, A, T.5.3 (55); WP.54 (119); WP.76 (123); THP.73 (I75) Collier, D, THP.188 (194) Colman, L, TP.30 (67) Colombe, B, WP.112 (129) Colombini, S, MP.25 (14) Colombo, S, MP41 (17); WP.58 (120); Conant, M, WP.112 (129); WP.219 (146); TH.8.5 (159); THP.S7 (173) Cone, L, MP.108 (28); TP.103 (79) Conklin, R, MP.217 (46) Connor, D, WP.168 (138) Connor, E, MP.162 (37); MP.170 (38); MP.213 (45); TP.170 (90); TP.215 (98); TP.226 (100); W.5.1 (108); WP.169 (138); WP.213 (145); THP.212 (198) Conte, J, TP.217 (98); WP.222 (147) Conviser, R, MP.208 (44); WP.174 (139) Cook, D, MP.196 (42) Cook, L, WP.243 (150) Cooke, M, TH.3.2 (154) Coombs, R, T.5.3 (55); WP.54 (119) Cooney, D, THP.10 (165) Cooper, B, THP.220 (200) Cooper, D, MR63 (20); MP.64 (20); MP.186 (41); TP.101 (79); WP.86 (124); WP.149 (135) Cooper, L, WP.65 (121 ) Cooper, R, T.4.6 (54) Copeland, T, M.9.3 (7); TP.21 (66) Copello, A, THP.194 (195) Corallo, S, THP.165 (191) Cordoba, S, T.7.4 (57) Corey, L, T.5.3 (55); WP.54 (119); E16 (206) Corless, I, TP.197 (95); WP.207 (144) Cornblath, D, MR66 (21); TP.140 (85) Comet, P, MR82 (23); W.2.4 (106) Corrigan, A, TP.242 (102); WP.21 (113); THP.245 (204) Cort, S, TP.108 (80) Cortes, E, TP.227 (100) Cosand, W, TP.32 (67) Cossaboom, M, WP.200 (143) Costa, C, THP.88 (178) Costin, C, MP.51 (18) Cottenot, F, MR98 (26) Cottone, J, MP.187 (41) Cottrell, M, WP.198 (143) Couderc, L, MP.148 (34); TP.216 (98); WP.228 (148) Coulaud, J, THP.169 (191) Coulits, T, WP.243 (150) Counihan, C, TP.156 (88) Coupal, L, MP.215 (46) Courouce, A, F.6.3 (211) Courtois, F, F.2.4 (207) Cousineau, E, WP.206 (144) Coutinho, R, M61 (4); MP53 (19); MP.74 (22); TP.40 (69); F85 (213) Cowan, M, MP.163 (37) Cox, D, WP.28 (115) Crabb, E, THP.121 (183) Craib, K, M.6.3 (5); MP.111 (28) Crane, C, WP.4 (111) Crapper, R, WP.92 (125) Craske, J, TP.250 (104) Crawford, J, W269 (121 ) Crawford, L, WP.212 (145) Creech, P, WP.70 (122) Criss, V, THP.242 (203) Critchley, S, MP.241 (50) Critchlow, C, THP.68 (174) Crocchiolo, P, TP.230 (100); WP.250 (152) Cronin, W, MP.106 (27); THP.110 (181); THP.152 (188) Cross, G, TP.108 (80) Crotti, D, WE95 (126) Crovan', P, TP.83 (76); WP.134 (132) Crowe, S, F93 (214) Crumpacker, C, WP.224 (I47); TH.4.6 (156) Crush-Stanton, S, TP.119 (82) Cuadrado, E, TP. 118 (82) Cumming, C, WP.22 (114) Cumming, S, TP.18 (65); WP.6 (111) Cunillera, C, TP.187 (93) Curran, J, T.1.1 (52); TP.84 (76); W.4.6 (108); WP.56 (119); WP.190 (142); THP.188 (194) 220 Curvin, M, 11112194 (195) Cusano, A, TP.148 (87) Cushion, M, MP.219 (46) Cusini, M, TP.164 (89); WP.161 (137) Cuthbert, R, MP.245 (51 ); TP.124 (83); TP.238 (102); WP.102 (127) Cutler, K, wmso (135); THP.56 (172) -D- Daffos, F, MP.189 (41 ) Daguillard, F, ”£92 (59); WP.85 (124) D’Agustino, F, WP.250 (152) Dahl Christensen, L, WP.229 (148) Dalakas, M, MP.144 (34); TP.151 (87); WP.223 (147) Dal Conte, I, MR41 (17) Dalgleish, A, M.4.3 (3); MP.20 (13); MP.122 (30); TP.3 (63) Damrosch, S, TP.172 (91) Dandekar, S, TP.36 (68) Daniel, M, F.7.3 (212) Danila, R, MP.193 (42); T.7.5 (57); WP.235 (149); THP.176 (192) Danner, S, MP.220 (46) D’Aquila, R, THP.44 (170) Darby, G, THP.22 (167) Dario, D, F.6.1 (211) Darr, F, TP.74 (74) Darragh, J, MP.225 (47) Darrow, W, M.3.1 (1); W.2.1 (105); E8.1 (213) Daugherty, D, M.9.4 (7) Davenny, K, MP.156 (36); WP.41 (117); TH.7.2 (157); THP.140 (186) Davey, M, TP.243 (103); WP.240 (150) Davidson, A, TP.70 (74); TR71 (74) Davidson, B, THP.228 (201) Davidson, J, THP.172 (192) Davidson, S, TP.205 (96); THP.172 (192) Davis, G, TP.9 (64) Davis, J, MP.182 (40); TH.4.4 (156) Davis, T, TH.11.2 (161) Davis, W, TH.5.1 (156) Dawson, G, WP.242 (150); E26 (207) Dax, E, WP.119 (130) Day, J, TP.47 (70); WP.88 (125) Day, S, THP.202 (197) Dayton, A, M.4.6 (3); T162 (62); THP.6 (164) Dana, M, T.5.4 (55); TP.37 (68); WP.32 (115); THP.33 (169); THP.75 (I76) D’Costa, L, M291 (25); THP.68 (174) Dean, L, THP.79 (176) de Andres, R, TR102 (79) De Biasi, R, TP.244 (103) Debouck, C, TP.100 ( 79) Debre, P, MP.123 (30) Debuono, B, MP.185 (41 ); TP.179 (92) De Castro, L, TP.187 (93) Decazes, J, THP.141 (187) Decker, B, THP.181 (I93) Decker, R, WP.242 (150) De Clercq, E, MR4 (10); T42 (54); TP.1 (62); TP.23 (66) De Cock, K, MP84 (24); TP.145 (86); WP.43 (117) De Goede, R, TP.33 (68); WP.125 (131) de Gruttola, V, THP.76 (176) Dehovitz, J, MP.136 (32) INDEX Deinhardt, F, T.46 (70); TH.10.6 (161); THP.93 (179) Deitch, D, WP.237 (149) De Jong, W, WP.180 (140) de la Barrera, S, MP.134 (32) Delagneau, J, MP.79 (23) De Lalla, F, THP.84 (177) de la Macorra, L, MP.173 (39) De La Monte, S, TP.129 (84) Delapenha, R, THP.179 (193) Delaporte, E, M.8.1 (5); WP.32 (115) Del Bono, V, WP.134 (132) De Leeuw, H, TP212 (97) DeLeo, M, MP222 (47) Delfin, M, MP.168 (38) Delorme, N, THP.164 (190) De Maria, A, TP.83 (76) Demeulemeester, R, MP.96 (26) de Miranda, P, WP.231 (148) Denis, F, E25 (207); E62 (211); F.6.6 (211) Denis, M, MP.123 (30) Denny, T, TP.226 (100); WP.169 (138) De Paoli, P, WP.95 (126) Deppe, D, M35 (2) De Rossi, A, MP.153 (35); TP.104 (79) Derrick, J, TP.243 (103); WP.240 (150) Deschamps, M, M.8.6 (6); MP.68 (21); MP.69 (21 ); MP.136 (32); TP.43 (69) Des Jarlais, D, MP201 (43); TP.69 (74); “11.4 (105); WP.180 (140); THP.67 (I74); THP.178 (193); THP.198 (196); THP.216 (199) Desmyter, J, MR4 (10); TP.23 (66) De Souza, Y, MP.223 (47); TP.138 (85) Desrosiers, R, MP72 (22); F.7.3 (212) Detels, R, TP.72 (74); TP.73 (74); WP.63 (120); WP.64 (121); THP.60 (173) de The, G, MP.117 (29); TP.153 (88) Dettke, T, TP.155 (88) Deutsch, M, MP.114 (29) Devare, S, F.2.6 (207) De Vathaire, F, THP.76 (176) DeVico, A, THP.97 (179) De Vinatea, M, TP.169 (90); WP.168 (138) De Wit, S, TP.82 (76); WP.59 (120) De Wolf, F, M61 (4); MP.53 (19); TP.100 (79); THP.136 (186) De Wolff, F, THP.126 (184) Diamond, G, TP.146 (86); W.5.3 (109) Dickinson, G, T.8.5 (58); W.2.2 (105); WP.91 (125); WP.167 (138); THP.92 (178) Dickson, D, W.5.3 (109) Diclemente, R, T.6.5 (56); WP.192 (142); THP.190 (195) Diecidue, R, MR41 (17) Dierich, M, MP99 (26) Dieterich, D, TH.4.5 (156) Dietrich, M, TP.155 (88) Dietrich, S, WP.245 (151) Difini, J, MP.139 (33) Digiovanni, C, MP.142 (33) Dijkgraaf, M, MP177 (39) Dillon, B, MP.192 (42); TP.185 (93); TP.239 (102) Di Lorenzo, A, WP.122 (130) di Marzo Veronese, F, THP.97 (179) Dinarello, C, F.9.2 (214) Diodato, S, WP.95 (126) Dittel, B, WP.9 (111) Divittis, A, THP.182 (193) Dix, R, TP.136 (85) Dobkin, J, F.3.2 (208) Dobson, A, MP.64 (20) Dock, N, WP.226 (148); THP.247 (204) Dodd, M, TP.197 (95); WP.207 (144) Dodd, R, MP.234 (49); THP.77 (176); THP.246 (204) Dodds, S, WP.196 (143) Doering, S, MP.181 (40) D’Offizi, G, TP.117 (82) Doherty, R, TP.18 (65); WP.6 (111) Doinel, C, THP.132 (185) Dolan, K, MP.186 (41) Doll, L, M.3.1 (1); F.8.1 (213) Domart, Y, F.2.4 (207) Donahue, R, MR222 (47); TP.122 (82) Dondero, T, T.7.3 (57); TP.84 (76); TP.179 (92); WP.56 (119); THP.77 (176) Dondero, Jr., T, WP.190 (142) Donegan, E, W.4.5 (108) Donovan, B, MP.63 (20) Dorfman, T, THP.6 (164) Dormont, D, TP.27 (67) Dorner, D, THP.59 (173) Dorsett, B, MP.106 (27); THP.110 (181) Dorsey, B, WP.119 (130) Dosik, M, THP.16 (166) Douglas, B, M.3.3 (2); M.6.3 (5); MP.111 (28); TP.99 (79) Douglas, D, W41 (107); WP.241 (I50) Dove, S, MP.187 (41 ) Dowbenko, D, WP.12 (112); WP35 (116) Dowling, H, MP.182 (40) Downer, A, TP.186 (93); TP.190 (94) Downs, A, THP.74 (175); THP.81 (I77) Dreesman, G, TP.3 (63); WP.107 (128); TH.9.5 (I60); THP.102 (180); E45 (209) Dreis, M, W.4.4 (108) Drew, H, TP.228 (100) Driscoll, J, T41 (54) Drotman, D, THP.188 (194) Drouet, L, MR98 (26) Drucker, E, TP.66 (73); WP.52 (119); TH.11.2 (161); TH.11.5 (162) Drury, F, WP.227 (148); THP.124 (184) Dudley, J, TH.5.6 (157) Duflo, B, TP.229 (100) Dugan, M, WP.230 (148) Duginski, T, MP.115 (29) Dukovich, M, E4.4 (209) Dukovitch, M, F92 (214) Duma, M, THP.18 (166); THP.19 (166); THP.139 (186); THP159 (190); E96 (214) Duncanson, F, TP.154 (88) Dunlop, N, MP31 (15) Dunnum, D, THP.186 (194) Durack, D, T.9.4 (59) Durand, J, M.8.1 (5); WP.78 (123) Durand, S, TP.142 (86) Durda, P, TH.9.1 (159) Dwyer, B, THP.31 (168) Dwyer, J, WP.225 (147); THP.115 (182) Dye, J, THP.194 (195) Dzwillo, G, WP.132 (132) —E— Eales, L, TP.111 (81) Earl, p, T.9.3 (59),- w.3.1 (106) 221 Earle, S, MP244 (50); TP.235 (101) Easley, K, THP.180 (193) Eaton, D, MP.150 (35) Eberle, J, TH.10.6 (161) Echaniz, P, TP.118 (82) Echenberg, D, THP.207 (198) Edson, R, MP.147 (34) Edwards, M, THP.87 (178) Edwards, V, MR84 (24) Eeftinck Schattenkerk, J, MP.220 (46); THP.126 (I84); THP.136 (186) Ehrlich, G, WP.23 (114); E23 (207) Eichberg, J, T.9.5 (59); WP.107 (128); THRZO (166); THP.102 (180) Eichnelaub, D, TP.157 (88) Eijrond, B, E85 (213) Einck, L, MR216 (46) Eisdorfer, C, MP.116 (29); THP.155 (189) Eisele, J, THP.82 (177) El-Beik, T, W.4.5 (108) El-Sadr, W, TP.163 (89); THP.69 (175); F.3.6 (208) Elder, G, MP.159 (36) Eldred, L, THP.119 (183) Elkin, C, WP.154 (136) Elkins, R, THP.249 (205) Ellis, M, THP237 (203) Elmslie, K, THP.72 (175) Emanuele, T, THR229 (201) Embree, J, WP.50 (118) Emerman, M, TH.2.1 (153) Emmanuel, J, M.8.3 (6); TP.68 (73) Emmons, C, T106 (60) Emsbroek, J, E85 (213) Eng, R, MP.160 (36) Englard, A, TP.223 (99); WP.218 (146) Engleman, E, MP.12 (12) Ensoli, B, M.9.5 (7); MR32 (15); TP.125 (83); THP.15 (166); THP.23 (167) Eppes, S, THP.235 (202) Epstein, A, WP.210 (145) Epstein, J, WP.129 (131); THP.52 (172) Epstein, L, MP.162 (37); THP.21 (167) Ercilla, C, MP.165 (37) Erfle, V, MP.104 (27); MP.166 (37) Ericson, B, W3.4 (107) Eron, L, MP.13 (12) Eskenazi, B, MP75 (22) Eskin, T, TP.149 (87) Essex, M, MP29 (15); TP.7 (63); WP.17 (113); WP.84 (124); TH.1.2 (153); TH.5.1 (156); TH.10.5 (161);TH.P.7 (164); F.6.6 (211) Esteban, J, WP.249 (I51) Etchebes, S, TP.79 (75) Evans, D, THP.143 (187) Evans, L, TP.130 (84); TH.2.6 (154) Evans, M, T72 (57) Evans, P, MR213 (45); TP.51 (71); TP.215 (98); WP.213 (145); THP.212 (198) Evans, W, TP.224 (99) Evatt, B, WP.82 (124) Even, P, THP.239 (203) Ewing, W, TP.247 (103) Eymard, D, THP.96 (179) Eyster, E, MP.65 (21) Eyster, M, MP.70 (21); TP56 (71); W.2.6 (106); E13 (206) INDEX _F_ Faber, V, M2113 (29); M2224 (47); W2229 (148) Fahey, J, M292 (25); T31 (53); T.9.6 (59); W264 (121); W2118 (130); W2129 (131); TH2121 (183) Fahrner, R, W2208 (145); TH.3.1 (154) Fainboim, L, M2134 (32) Falcke, H, M242 (17) Falk, L, T2225 (100); W29 (11]); TH2101 (180) Falkner-Gunter, F, W3.1 (106) Faltz, B, T2203 (96); TH2218 (I99) Falutz, J, TH2133 (185) Fang, C, M2234 (49) Fannin, S, TH251 (I72) Fanning, M, M249 (18); M250 (18); M2209 (45); T2224 (99); TH.4.3 (155); TH.8.1 (158); Faraone, N, M2185 (41) Farber, B, W2158 (I36); TH216 (166) Farber, C, M2124 (30) Farthing, C, M.6.4 (5); TH2237 (203) Farzadegan, H, M266 (21); T31 (53); W266 (121) Fauci, A, M2103 (27); M2228 (48); T22 (52); "28.2 (58); T93 (59); T296 (78); T2106 (80); W5.4 (109); TH2109 (181); TH2226 (201); 24.4 (209); 29.2 (214) Faulkner-Valle, G, T2104 (79) Faure, G, M2118 (29); TH2164 (190) Fearns, M, M255 (19) Feck, J, TH270 (175) Fehniger, T, M2214 (45) Feigal, D, T244 (69); W247 (118); W258 (120); W2150 (135); TH256 (172); TH257 (173); TH2154 (189); 23.1 (208); 23.3 (208) Feigal, E, T2115 (81) Feinberg, J, M2228 (48) Feiner, C, T267 (73); W25 (106); TH2197 (196) Feingold, A, M2156 (36); TH.3.3 (154); TH.7.2 (157); TH241 (170); TH2140 (186) Feldman, H, T2176 (91); W2197 (143) Feldman, I, T2209 (97) Felgenhauer, K, T2157 (88) Fennie, C, M.4.4 (3) Fenyo, E, M.10.6 (8); M211 (12); TH213 (I65); TH229 (168); Fenyo, E, T2132 (84) Feorino, P, W2181 (140); TH228 (168); TH242 (170) Ferchal, F, M2149 (35) Ferguson, B, T235 (68); W228 (115); TH226 (167); TH227 (168) Fermosel, J, M2167 (38) Fernandez, A, W296 (126); W2120 (130) Fernandez-Cruz, E, W296 (126); W2120 (130) Fernando, L, W2175 (139) Ferris, S, M280 (23) Fertel, D, T2168 (90) Fiala, M, M2108 (28); T2103 (79) Fields, H, TH2119 (183) Figueroa, P, T48 (70) Fikrig, S, W2169 (I38); W2170 (138) Finaud, M, T.5.6 (55) Fior, R, TH2123 (184) Fioravanti, D, W2122 (130) Fischel, M, T.8.3 (58) Fischer, A, M2166 (37) Fischinger, P, M.10.2 (8); M231 (I5); T210 (64); W3.6 (107); W23 (110); 27.6 (212) Fischl, M, M238 (16); T238 (68); T2136 (85); T2232 (101); W22 (105); W291 (125); W2105 (127); W2167 (138); W2223 (147); TH292 (178); TH2240 (203) Fishbach, R, TH2150 (188) Fishbein, D, TH242 (170) Fisher, A, M95 (7); M223 (14); W3.5 (107); W220 (113) Fishinger, P, M217 (13) Fitzgerald, R, M2248 (51); W2246 (151 ) Fitzgerald-Bocarsly, P, W2109 (128) Fitzhugh, Z, TH.3.4 (155) Flack, S, T2198 (95) Flageul, B, M298 (26) Flanagan, S, W2.2 (105); TH292 (I78) Flaviano, A, M246 (17) Fleisher, E, W270 (122); TH266 (I74) Fleming, A, M277 (23); W2145 (I34) Fletcher, C, T2231 (101) Fletcher, M, M2116 (29); M2246 (51); W22 (105 ); W2105 (127); W2196 (143); TH2240 (203) Fletcher, W, W2202 (144) Flexner, C, W3.1 (106) Flodby, P, M239 (16) Flye Sainte Marie, F, T295 (78) Flynn, N, M2191 (42); T2184 (93); W2175 (139); TH2215 (199) Flynn, T, W2158 (136) Foeste, W, W2227 (148) Folks, T, M94 (7); M222 (13); T2106 (80); T2133 (84); W34 (107); TH2109 (181); 29.2 (214) Follett, E, TH2244 (204) Fonina, L, M297 (26) Forbes, C, T2241 (102); W2238 (I50); TH2244 (204) Ford, R, M234 (I5) Fordycebaum, M, M2116 (29) Forestier, F, M2189 (41 ) Forlenza, S, W229 (115) Formany, A, W2179 (140) Forrest, K, W2192 (142) Forsberg, A, M.11.4 (9); M2240 (50); T2144 (86) Forstein, M, T2178 (92) Forster, S, T2111 (81) Forthal, D, W243 (117) Foss, B, TH.5.1 (156) Foster, C, T2195 (95) Foucault, C, W287 (124) Foult, J, T2165 (90) Fouret, P, M2158 (36) Fox, P, M2152 (35) Fox, R, T272 (74); T273 (74); W267 (121); TH.5.6 (157); TH264 (174); 28.4 (213) Foy, J, M2219 (46); T274 (74) Francavilla, E, T2104 ( 79) France, A, M2137 (33) Franchini, G, M233 (I5); T215 (65) Francis, D, T2152 (87); W45 (117); TH.5.3 (I56); TH2181 (193) Francis, H, M36 (2); M261 (20); M273 (22); T76 (57); T2145 (86); W46 (108); W284 (124); W2136 (I33); TH.7.6 (158); TH218 (166); TH219 (166); TH2139 (186); 29.6 (214) 222 Francis, R, TH2200 (196) Frank, B, M2146 (34) Fratantoni, J, T2245 (103); W4.4 (108) Fraulino, L, T2150 (87) Frazer, 1, W292 (125) Fredenburg, L, TH2229 (201 ) Frederick, W, T2242 (102); TH2179 (I93); TH2245 (204) Frederiksen, B, M262 (20) Freeman, A, W2187 (141) Freeman, K, M2155 (36); TH.3.3 (154); TH.3.5 (155) Freeman, W, T2160 (89) Freese, U, T2138 (85) French, J, W2.1 (105); TH2196 (196); T257 ( 72) Frenkl, T, M2238 (49) Frenzel, B, T225 (66) Frenzel, G, F.4.5 (209) Freudenberg, N, M2176 (39) Friedland, G, M.3.4 (2); M2155 (36); T267 (73); T2143 (86); W241 (117); TH.3.5 (155); TH.4.6 (156); TH.11.6 (162); TH241 (170); TH2197 (I96) Friedman, E, M2157 (36) Friedman, S, M2201 (43); T269 (74); W2180 (140); TH267 (I74); TH2178 (193); TH2198 (196) Friedman-Kien, A, W2133 (132); TH29 (165) Frisby, H, 25.2 (210) Frosner, G, M2166 (37); TH293 (179) Fuchs, D, T287 (77); M299 (26); TH2166 (I91) Fuerst, T, W3.1 (106) Fulilove, M, W2178 (140) Fultz, 2 M227 (14); M272 (22); 27.1 (212); 27.2 (212) Fung, M, T211 (64) Fung, S, T211 (64) Fusillo, C, M290 (25) Fiist, G, M221 (13); M2236 (49) _G_ Gabuzda, D, T2129 (84); W2139 (133) Gadelle, S, T237 (68); TH233 (169) Gadol, C, T2170 (90) Gadow, A, T225 (66) Gage, L, W2211 (I45) Gage, P, T217 (65) Gajdusek, D, T229 (67) Galbraith, N, W294 (126) Galibert, F, W237 (116) Gallagher, K, M2168 (38) Galli, M, T2230 (100); W289 (125); TH284 (177) Gallo, R, M21 (1); M217 (13); M223 (I4); M225 (I4); M232 (15); M233 (15); M234 (15); M2131 (32); T33 (53); T164 (62); T.120 (82); T219 (65); T220 (65); T221 (66); T2125 (83); T2132 (84); W33 (107); W3.5 (107); W3.6 (107); W25 (III); W220 (113); W2128 (131); TH.2.3 (153); TH.2.4 (I54); TH.9.1 (159); TH23 (164); TH215 (I66); TH223 (167); TH297 (179); 29.1 (214) Galloway, W, T2195 (95 ) Ganfield, M, M236 (16) Gangadharam, 2, W269 (121); TH2147 (188); TH2157 (I89) INDEX Ganjei, P, THP.143 (187) Gantz, N, WP.171 (138) Garcia, N, WP.70 (122); WP.71 (122) Garcia Montes, M, WP.120 (130); WP.96 (126) Garcia-Fons, F, WP.127 (131) Gard, E, T219 (65) Gardner, L, MR81 (23); T.7.1 (57); T50 (70) Gardner, M, MP.230 (48); TP.6 (63); TP.28 (67) Gardner, T, MP.141 (33) Garfinkle, J, TP.169 (90) Gamer, J, WP.237 (149); THP.53 (172) Garovoy, M, WP.112 (129) Garrigue, G, WP.78 (123) Garry, R, THP.112 (182) Garsia, R, MP.168 (38) Gartner, S, MP.104 (27); MP.131 (32); TP.107 (80); T120 (82); F.9.1 (214) Garvey, M, TP.224 (99) Garzon, S, MP.102 (27) Gastaut, J, T.5.6 (55) Gaston, I, TP.130 (84) Gatenby, P, MP.168 (38) Gates, F, E42 (209) Gaub, J, MR224 (47) Gaynor, S, MP247 (51) Gazengel, C, MP.45 (17) Gazit, E, TH.10.5 (161) Gazzard, B, M.6.4 (5); MP.141 (33); THP.237 (203) Geary, J, TP.196 (95 ) Gehan, K, THP.228 (201); THP.233 (202) Gelderblom, H, TP.24 (66) Geltosky, J, MP.107 (28) Gendelman, H, MP.19 (13); MP22 (13); F.7.4 (212) Genesca, J, WP.249 (151) Gentilini, M, TP.229 (100); WP.79 (123); THP.24 (167) George, A, MP.171 (38) George-Nascimento, C, T121 (82) Georges, A, M.8.1 (5); MP37 (16); MP.164 (37); TP.79 (75); WP.77 (123) Georges-Courbot, M, MP.164 (37); TP.79 ( 75 ); WP.77 (123) Georgoulias, V, MP.112 (28); F.4.6 (209); F.9.4 (214) Gerard, H, THP.164 (190) Gerard, J, MP.154 (35) Gerber, M, WP.189 (141) Gerbert, B, THP.213 (199) Gershy-Damet, G, F25 (207); E62 (211) Gerstoft, J, T.3.5 (53); TP.123 (83) Gervais, F, TP.89 (77) Gesemann, M, THP.131 (185) Geurts, J, MP.177 (39) Gharakhanian, C, M.5.4 (4) Gharakhanian, S, TP.229 (100); F21 (207) Ghazzouli, I, THPS (164) Ghirardini, A, THP.248 (204) Ghrayeb, J, TP.28 (67); TP.132 (84) Gianakakos, V, TP.110 (80) Giaquinto, C, MP.47 (18); MP.153 (35); TP.104 ( 79) Gibbons, J, W.3.3 (107); WP.11 (112) Gibbs, C, TP.29 (67); WP.18 (113) Gibbs, W, T48 (70) Gibson, P, WP.178 (140) Gibson, S, MR217 (46) Gigase, P, THP.227 (201) Gilden, R, TP.10 (64); THP.34 (169); F.7.6 (212) Giles, M, THP.51 (172) Gill, P, W21 (105); WP.146 (134); WP.215 (I46); THP.49 (171); THP.96 (I79); THP.144 (187) Gilman, T, THP.151 (188) Gilmore, N, MP215 (46); WP.215 (146); THP.96 (I79) Gilson, I, TH.8.5 (159) Gindi, E, MR90 (25) Gindo, A, MPSO (23) Gingeras, T, TP.9 (64) Ginzburg, H, TP.87 (77); F.6.5 (211) Giorgi, J, T96 (59); WP.117 (129); WP.118 (130); THP60 (173); THP.121 (I83) Giovanni, C, MP.198 (43) Giraldo, G, TP.244 (103) Girard, M, THR32 (168) Girard, P, MP.161 (37); TP.165 (90); TP.216 (98); WP.160 (I37); WP.228 (148); THP.169 (191); THP.170 (191) Giri, C, TP.16 (65) Giuliani, G, MP.41 (17) Gjerset, G, WP.54 (119); THP.50 (171) Glover, L, T.6.4 (56) Gluckman, J, M.10.1 (7); TP.105 (80); TH.9.6 (160) Gluckmann, J, WP.87 (124) Goebel, F, MP.166 (37); TP.213 (98); WP.165 (137) Goeddel, D, T45 (54) Goedert, J, MR65 (21); MP.70 (21); T.3.3 (53); TP.56 (71); TP.87 (77); W26 (106); TH.7.3 (158); THP.71 (175); E12 (206) Goh, W, T.4,3 (54) Gold, J, MR64 (20); MP.186 (41); THP.222 (200) Gold, P, TP.89 (77); WP.163 (137); THP.133 (185) Goldberg, E, THP.96 (179) Golde, D, MP.222 (47) Golden, J, TP.217 (98) Goldfinger, D, MP.169 (38) Goldfinger, S, THP.167 (I91) Golding, B, E42 (209) Golding, H, F.4.2 (209) Goldman, E, MP.76 (22) Goldsmith, D, WP.180 (140); THP.198 (I96) Goldstein, A, MR24 (14); TP.134 (84); WP.18 (113); THP.107 (181); THP.128 (184) Goldstein, D, MP.248 (51 ); WR246 (151) Goldstein, L, WP.65 (121); THP.52 (172) Goldwater, P, MP204 (44) Gomperts, E, MP.138 (33) Gonda, M, M.10.2 (8); MP.13 (12); TH25 (154); Gonda, M, THP.34 (169) Gonzalez, J, TP.79 (75); WP.77 (123); WP.93 (125); THP.59 (173) Gonzalez-Porque, P, TP.118 (82) Good, R, F.4.1 (209) Gootenberg, J, MP.126 (31 ) Gordon, L, TP.199 (95); TH.11.5 (162) Gorman, E, TP.59 (72); THP.181 (193) Gorman, R, MP.225 (47) Gornitsky, M, MP.102 (27) Gottleb, M, THP.241 (203) Gottlieb, A, MP218 (46); TP.228 (100); THP.241 (203) 223 Gottlieb, M, MP.109 (28); MR218 (46); TP.127 (83); TP.228 (100); WP.103 (127); THP.232 (202) Gotzsche, P, WP.229 (148) Goudeau, A, WP.27 (114) Goudsmit, J, M.6.1 (4); MP9 (11); MP.S3 (19); TP.33 (68); TP.40 (69); TP.100 (79) Gougerot-Pocidalo, M, TP.126 (83) Gourley, P, WP.182 (140) Gowan, L, TP.248 (103) Gowda, S, MP.12 (12) Grabau, J, TP.177 (92) Gracie, J, TP.241 (102); WP.238 (150); THP.244 (204) Grade, M, TP.203 (96); THP.218 (199) Grady, C, THP.219 (200) Grady, G, THP.175 (192) Graham, D, W.4.4 (108) Graham, J, THP.195 (196) Graham, V, WRZOO (143) Grant, I, MP.145 (34); MP.200 (43) Grape, R, MP.140 (33) Grassi, F, WP.124 (131) Grassi, M, WP.143 (134) Grassi, P, WP.144 (134) Gravell, M, MP.144 (34) Gray, J, THP.172 (192) Greaves, W, THP.179 (193) Green, J, MP205 (44); T62 (56); THP.162 (190) Green, L, MP.185 (41) Greenberg, A, M.8.5 (6); MR73 (22); TP.139 (85) Greenberg, R, MP.199 (43) Greenblatt, R, THP.47 (171); THP.68 (174) Greene, W, F.4.4 (209) Greenspan, D, MP.223 (47); TP.138 (85); WP.58 (120) Greenspan, J, MP223 (47); TP.138 (85 ); WP.58 (120); WP.112 (129) Gregg, R, WP.129 (131) Gregory, T, M.4.4 (3); WP.12 (112); THP.20 (166) Grieco, M, MR90 (25); TP.223 (99); WP.218 (146); THP.62 (173) Grieve, W, THP.142 (187) Griffin, D, MP66 (21) Griffin, J, TP.140 (85) Griffiss, J, THP.163 (190) Griffiths, C, MP.171 (38) Griffiths, P, MP76 (22); TP.233 (101) Grifol, M, MP.165 (37); TP.167 (90) Grigoriu, A, WP.60 (120) Grimaila, R, WP.33 (115) Grimes, J, WP.53 (119) Grimfeld, A, MP.117 (29) Grindon, A, MP.241 (50); W.4.1 (107) Grint, P, MP67 (21) Griscelli, C, TH.7.4 (158) Gritti, F, TP.113 (81) Groen, G, TP.63 (73) Groh, V, TP.107 (80) Groopman, J, MR89 (25 ); M8222 (47); TP.17 (65); TP.64 (73); TP.122 (82); TH.5.1 (156); THP.20 (166) Grosch-Worner, I, MP.47 (18); THP.94 (179) Gross, M, TP.178 (92) Gross, S, WP.178 (140) INDEX Gross, W, MP.100 (26); MP.101 (27) Grossman, R, MP65 (21) Grover, S, MR215 (46) Growe, G, WP.163 (137) Gruttola, V, MP52 (18) Gschwind, C, WP.131 (132) Guerois, G, WP.27 (114) Guerra, C, THP.85 (177) Guigli, P, WP.155 (136) Guillon, J, MP.123 (30) Guinan, M, THP.54 (172) Gunnel, B, THP.29 (168) Gunson, H, MP233 (49) Guo, C, WP.20 (113) Guo, H, MR33 (15) Gupta, P, WP.106 (128) Gurbindo, D, WP.96 (126) Gurbindo, M, MP.167 (38) Gurgo, C, MP33 (15); MR34 (15) Giirtler, L, T46 (70); TH.10.6 (161); THP.93 (179) Gust, I, THP.31 (168) Gutierrez, C, WP.120 (130) Gutzwiller, F, MP.179 (40) Guyader, M, TH.2.1 (153) Guyton, R, TP.22 (66) Gyenes, A, T121 (82) _H_ Habermehl, K, TP.34 (68); WP.26 (114); THP.25 (I67) Haburchak, D, MP.140 (33) Haddadian, A, WP.103 (127) Hadley, W, TP.219 (99); THP.163 (190) Haffar, O, WP.25 (114) Hahn, B, WP.11 (112); TH.2.3 (153) Halabi, F, TH.9.6 (I60) Haley, C, TP.77 ( 75); WP.187 (I41); THP.221 0M» Haley, R, THP.221 (200) Hallberg, P, M.5.1 (3) Hallick, L, WP.34 (116) Halloran, P, TH.4.3 (I55) Halsey, N, THP.63 (I74) Hamamoto, Y, MP235 (49) Hamerschlack, N, THP.85 (177) Hamilton, P, MP.55 (19) Hammarskjold, M, MP.30 (15) Hampe, A, WP.37 (116) Hampl, H, WP.26 (114) Handsfield, H, T.5.3 (55); TH.4.6 (156); WP.76 (123); THP.73 (I75); F.1.6 (206) Hankins, C, WP.179 (140) Hannon, R, MP.140 (33) Hanrahan, J, THP.70 (175) Hansen, J, THP.36 (169) Hansen-Sparks, W, F86 (213) Hanson, M, MP237 (49) Harada, S, M.4.2 (2); MR235 (49) Harding, R, TP.45 (70) Hardy, A, MP.89 (25); THP.54 (172) Hardy, D, THP.232 (202) Harmon, T, MP209 (45) Harper, M, WP.241 (150) Harper, S, MP.191 (42); TP.184 (93); WP.175 (139); THP.215 (I99) Harris, B, THP.180 (I93) Harris, C, W.2.5 (106) Harris, J, THP.101 (180); THP.202 (197) Harrison, S, MP.140 (33) Harrison, W, TP.135 (85); TP.156 (88) Hartel, D, M.3.4 (2); WP.41 (117); THP.41 (170) Hartshom, K, TP.30 (67); WP.104 (127) Hartzman, R, THP.109 (181) Harvey, E, MP.150 (35) Harzic, M, MP.149 (35); TP.37 (68); WP.138 (133); THP.33 (169); THP.75 (I76); F.2.4 (207) Haschke, F, TH.10.4 (161) Haseltine, W, M.4.6 (3); M.9.2 (7); T43 (54); T.16.2 (62); WP.16 (113); WP.38 (116); THP.6 (164) Haskin, J, T.6.5 (56) Hassig, S, MP.184 (40) Hatch, W, MP31 (15) Hattori, T, W.3.2 (106) Hauer, L, WP.S7 (119) Hausen, A, MP99 (26) Hausler, W, MP.129 (31) Hausmann, E, TP.24 (66) Hawkins, J, THP.53 (172) Hayami, M, MP28 (14); MR94 (25); THP.65 (174) Hayward, G, WP.38 (116) Hazan, U, MR37 (I6) Hazel, E, F.3.2 (208) Hazell, E, T.6.1 (56) Heagarty, M, TH.11.3 (162) Hearn, J, TP.4 (63) Hearst, N, WP.150 (135); THP.56 (172) Heckert, K, TP.189 (94); THP.176 (192) Hedderman, M, TH.11.1 (I61) Hedley-Whyte, E, TP.129 (84); WP.139 (133) Hegarty, J, TH.11.3 (162) Hehlmann, R, MP.166 (37) Heimer, E, MR238 (49) Heisterkamp, S, MP.74 (22) Héjjas, M, MR236 (49) Helgerson, S, TP.181 (92) Heller, J, F.2.6 (207) Henco, K, WP.24 (114) Henderly, D, TP.160 (89) Henderson, L, M93 (7); THP.112 (182) Hendrickson, E, WP.28 (115) Hendrix, H, MR219 (46) Hendry, R, MP.125 (31 ); THP.122 (183) Hengy, C, M.8.1 (5) Henin, Y, THP.37 (169) Henriques, H, MP216 (46) Henry, K, MP.193 (42) Herbold, J, T71 (57); THP.77 (I76); F.1.1 (206) Herbst, J, MP.146 (34); TP.141 (86) Herdewijn, P, MR4 (10) Hermans, P, TP.82 (76); WP.59 (120); THP.61 (173) Hernandez, J, WP.249 (151 ) Hernandez, M, TP.147 (87); THP.234 (202) Hernandez Sampelayo, T, MP.167 (38) Herndon, K, TP.77 (75) Herpin, B, MP.228 (48); WP.205 (144) Herrera, M, TP.102 (79) Hersh, E, M2225 (47); TP.218 (98); WP.131 (I32) Herve, P, MP.148 (34) Heseltine, P, T85 (58); WP.221 (I47); TH.11.1 (161); THP.149 (188); THP.151 (188) 224 Hess, E, WP.133 (132) Hesselink, J, T83 (58); TP.158 (88) Hessol, N, M.3.1 (1) Heutink, P, TP.100 ( 79) Higgins, B, MP.199 (43) Higgins, J, MP.151 (35 ) Hildebrandt, D, MP.83 (24) Hill, J, M.5.1 (3) Hill, T, MP.107 (28) Hingson, R, T.6.6 (56) Hinuma, Y, M.4.2 (2) Hirsch, A, TP.142 (86) Hirsch, D, T105 (60) Hirsch, M, T91 (59); TP.30 (67); TP.129 (84); WP.104 (127); WP.139 (133); TH.4.6 (156) Hirsch, V, TH.2.2 (153); WP.15 (112); THRS (164) Hirschmann, M, WP.152 (135) Hittelman, J, THP.158 (189) Hitzeman, R, WP.3S (116) Ho, D, TP.129 (84); WP.139 (133) Ho, E, E75 (212) Ho, M, THP.60 (173) Hoban, M, THP.146 (187) Hobusch, G, MP.101 (27) Hodge, J, TP.179 (92) Hodges, R, THP.128 (184) Hoff, C, WP.50 (118) Hoff, R, THP.175 (I92) Hoffken, G, WP.132 (132) Hoffman, P, THP.12 (165) Hoffman, R, TP.58 (72) Hofmann, B, TP.123 (83); WP.101 (127); WP.162 (137) Hojvat, S, WP.44 (117); THP.9 (165) Hollan, S, MP21 (13); M2236 (49) Holland, B, W.5.1 (108) Holland, J, T.10.5 (60); W.5.6 (109); WP.115 (129) Holland, P, M35 (2); WP.175 (I39); MP.120 (30); MP.151 (35); T55 (55); TP.121 (82); TP.217 (98); WP.58 (120); TH.8.4 (159); TH.9.2 (159); THP.57 (173) Hollinger, F, THP.114 (I82) Holman, S, TP.78 (75); WP.157 (136); TH.7.3 (158); THP.158 (189); THP.209 (198); Holmberg, S, MP241 (50); W.4.1 (107); TH.10.1 Ha» Holt, E, THP.63 (174) Holtzman, D, THP.45 (171); THP.83 (177) Holzemer, W, TP.207 (97) Holzman, B, THP.167 (191) Holzman, R, WP.147 (134); THP.214 (199) Homsy, J, TP.130 (84); WP.14 (112) Honey, E, WP.200 (143) Hong, T, TP.68 (73) Honnen, W, TP.110 (80) Hood, H, MP.174 (39); MP.196 (42) Hooykaas, C, MP53 (19) Hopewell, P, E33 (208) Hopkins, D, WM (105) Hopkins, S, TP.186 (93); WP.49 (118); WP.88 (125) Hopkins, W, THP.198 (196) Hording, M, WP.229 (I48) Horsburgh, C, TP.7O (74) Horvath, A, MP.21 (I3) INDEX Horwitz, S, TP.77 (75) Hosein, B, TP.240 (102); WP.236 (149); THP.243 (204) Hoshino, H, WP.31 (115) Hoshino, T, WP.103 (127) Houff, S, MP.159 (36) Houghton, R, MP.35 (16); TP.32 (67) Houk, R, MP.115 (29); WP.156 (136) Hovanessian, A, TP.5 (63) Howard, J, MP.175 (39) Howard, L, WP.173 (139) Howard, T, TP.246 (103) Hryb, K, THP.220 (200) Hsu, A, MP.18 (I3) Hu, S, T.9.5 (59); WP.39 (116) Huhtala, M, TH.9.3 (I60) Huisman, H, THP.90 (I78) Huisman, J, TP.33 (68); TP.92 (77); WP.36 (116) Hull, H, THP.186 (194) Hull-Drysdale, B, F.6.4 (211) Hulley, S, T.10.1 (60) Hummel, R, TP.209 (97) Humphreys, P, TP.243 (103) Hunsmann, G, MR28 (14) Hunt, J, WP.242 (I50) Huprikar, J, T.3.6 (53) Hurd, G, THP.184 (194) Hurzeller, R, WP.214 (146) Hussey, S, WP.224 (I47) Hutchinson, V, TH.11.3 (162) Hutto, C, MP38 (16); E22 (207) Hutto, S, WP.166 (138); THP.91 (178) Huyghen, K, MP.124 (30) Hyldig-Nielsen, J, WP.101 (127) -1— Icardi, G, WP.134 (132) Iijima, H, MP.235 (49) Illeman, M, WP.219 (146) Imagawa, D, MR8 (11); THP.160 (I90) Imam, F, THP.3 (164) Imperato, D, TP.68 (73) Imrie, A, MP.186 (41) Inada, Y, THP.62 (173) Intrator, L, THP.123 (184) Ioachim, H, MP.106 (27); THP.110 (181); THP.152 (I88) Ioannou, S, TP.175 (91) Ippolito, G, TP.93 (78); WP.248 (151) Ischenko, A, WP.98 (126) Iseman, M, THP.147 (188) Ishikawa, Y, MR94 (25); THP.65 (174) Itoua—Ngaporo, A, Wp.79 (123) Ivanoff, L, M.9.5 (7) _J_ Jackson, J, MR210 (45); TH.5.2 (156); TH.11.4 (162) Jacob, J, WP.147 (134); THP.219 (200) Jacobs, R, WP.183 (140); TH.8.4 (159) Jacobsen, P, MP.195 (42) Jacobson, D, TP.61 (72); WP.234 (I49) Jacobson, M, MP.221 (47); WP.231 (148) Jacobus, D, THP.231 (202) Jacquette, G, E32 (208) Jaeger, H, T46 (70); THP.166 (191) Jaenisch, R, TP.62 (72) Jaffe, H, M.3.l (1); MR83 (24); MP.127 (31);W.2.3 (106); E81 (213) Jaffe, J, MP.74 (22); TP.54 (71); WP.119 (130); THP.74 (175); THP.95 (179) Jagodzinski, L, MR25 (14) Jain, S, MP.191 (42); TP.184 (93); WP.175 (139); THP.215 (199) Jairam, B, THP.157 (189) Jakobovitz, A, TP.31 (67) Janett, A, MP.56 (19) Janier, M, MR98 (26); TP.216 (98) Janossy, G, WP.137 (133) Jansen Schoonhoven, F, F.8.5 (213 ) Janssen, R, T.5.2 (55) Jarrett, W, T21 (52); TP.19 (65) Jarry, A, MP2 (10) Jarvik, J, TP.158 (88) Jasmin, C, MP.112 (28); E4.6 (209); F94 (214) Jason, J, WP.82 (124) Jayle, D, THP.106 (181) Jean-Charles, M, TP.43 (69) Jeannequin, 0, "IRS (63) Jeffries, D, TH.4.4 (156); TH.8.3 (159) Jelesoff, N, M.5.1 (3) Jellis, C, THP35 (169) Jendis, J, THP.14 (165) Jennings, A, T.3.3 (53) Jennings, M, TP.6 (63); TP.28 (67) Jensen, F, MP34 (15) Jesson, W, M.6.4 (5) Jett, K, MR85 (24) Joffe, R, THP.146 (187) Job], S, MP.18 (13) Johns, D, T42 (54); TP.1 (62) Johnson, A, TP.179 (92) Johnson, D, TP.188 (93) Johnson, E, MP.160 (36); THP.171 (192) Johnson, J, MR49 (18); MP50 (18); MR85 (24); WP.123 (130) Johnson, M, TP.122 (82) Johnson, R, MP.66 (21) Johnson, S, MESS (19); THP.31 (168) Johnson, W, M.8.6 (6); MP.68 (21); MP.69 (21); MP.136 (32); TP.43 (69) Joist, J, THP.127 (184) Jondal, M, M.10.6 (8) Jones, B, THP.100 (180) Jones, F, MR231 (48) Jones, M, MP.137 (33) Jones, P, MP.55 (19); TH.8.5 (159) Jones, T, TP.182 (92) Jones-Mangione, E, TP.58 (72) Jomvall, H, MR39 (16) Josefberg, H, THP.231 (202) Joseph, J, T.10.6 (60) Josephs, s, MP23 (14); TP.11 (64); TH.2.4 (154),- THP.242 (203) Josephson, S, MP.129 (31 ) Joshi, V, MP.162 (37); MP.170 (38); TP.170 (90); W51 (108); WP.169 (I38) Josse, R, M.8.1 (5); WP.78 (123) Jothy, S, WP.215 (I46); THP.96 (179) Jouvin, M, WP.126 (131) Jubran, A, WP.140 (133) Judkins, K, MP.125 (31) Judson, F, TP.70 (74); TP.71 (74); WR181 (140); WP.182 (140); THP.58 (173) 225 Julander, I, THP.238 (203) Junca, J, TP.167 (90) Jung, M, MP.46 (17) Jupp, P, MR40 (16) Jurkiewicz, E, MR28 (14) Justement, J, TP.106 (80); E92 (214) _K_ Kabote, N, M.8.5 (6); MP.73 (22) Kahl, P, TP.67 (73); THP.197 (196) Kahn, A, WP.195 (142) Kahn, D, TP.169 (90) Kain, S, WP.61 (120) Kamani, N, THP.122 (183) Kamradt, T, THP.168 (I91) Kanda, P, THP.102 (180); E45 (209) Kang, E, MR243 (50) Kanki, P, MP29 (15); TP.7 (63); THP.7 (164);; F.6.6 (211 ) ' Kannagi, M, THP.104 (180); F.7.3 (212) Kanouse, D, TP.59 (72); THP.181 (193) Kapila, R, MP.160 (36); WP.60 (120) Kapita, B, M.3.6 (2); T.7.6 (57) Kaplan, C, WP.180 (140) Kaplan, J, T.5.2 (55); THP.42 (170) Kaplan, L, M.11.2 (9); M.11.3 (9); TP.115 (81) Kaplan, M, WP.158 (136); WP.159 (136); THP.3 (164); THP.16 (166) Kaplowitz, L, TP.208 (97) Kappatos, D, W.5.6 (109) Kappel, S, THP.192 (195) Karaffa-Myles, C, TP.162 (89); WP.222 (147) Karamov, E, WP.98 (126) Karlsson, A, MR93 (25); WP.83 (124); THP.130 (I85) Karp, M, F56 (210) Karty, R, WP.34 (116) Kasali, M, THP.18 (166) Kashkin, J, TP.146 (86) Kasili, E, TP.249 (104) Kaslow, R, TP.72 (74); TP.73 (74); WP.67 (121); TH.5.6 (157); THP.64 (174) Katlama, C, T54 (55); WP.160 (137); THP.24 (167); THP.75 (176); F.6.1 (211) Katoff, L, WP.203 (144) Katona, I, MP.133 (32) Katz, D, MP.159 (36) Katz, J, TP.127 (83); Katz, J, WP.103 (127) Katz, S, THP.16 (166) Katzenstein, D, M.8.3 (6) Katzmann, J, MP.147 (34) Kauffman, S, WP.169 (138); WP.170 (138) Kaufman, F, MP.138 (33) Kaufman, J, TP.16 (65 ) Kaufman, N, E52 (210) Kaufmann, M, MR56 (19) Kay, J, WP.247 (151) Kayembe, K, MP.61 (20) Keddie, E, MP.191 (42) Kegeles, S, THP.185 (194) Keiser, J, WP.152 (135) Keith, D, 119.6 (59) Kekow, J, MP.100 (26); MP.101 (27) Kelen, G, TH.3.6 (I55) Keller, A, MP.46 (17) Keller, G, WP.21 (113); WP.22 (114) Keller, N, THP.186 (194) INDEX Keller, S, WP.165 (137) Kelley, P, T.50 (70); F.1.1 (206) Kellie, S, MR68 (21) Kelliher, J, F.7.6 (212) Kelly, J, MP.174 (39); MP.196 (42); WP.199 (143); THR249 (205) Kemp, B, TP.18 (65); WP.6 (111) Kenealy, W, MP36 (16); TP.23 (66) Kennedy, C, MP.145 (34); MR200 (43); T.8.3 (58); TP.61 (72); TP.158 (88); WP.234 (149) Kennedy, M, MP.127 (31); TP.3 (63); TP.108 (80); WP.113 (129); TH.9.5 (160); THP.102 (180); F.4.5 (209) Kenny, D, MP.168 (38) Kenrick, K, WP.243 (150) Keresztes, J, TP.215 (98); TP.226 (100); WP.213 (145); THP.212 (I98) Kern, C, MP.218 (46); THP.241 (203) Kern, P, MP.100 (26); MP.101 (27); TP.155 (88) Kernoff, P, MP.76 (22); TP.233 (101); WP.137 (133); Kessler, H, TP.225 (100); WP.9 (111); THP.101 (180) Kessler, R, T.10.6 (60) Ketlinsky, S, WR98 (126) Keur, W, TP.63 (73) Keys, T, TP.162 (89) Khaitov, R, MP97 (26) Khan, N, THP.99 (180) Khillan, J, F.7.4 (212) Khoury, E, WP.112 (129) Kiango, J, TP.86 (76) Kienny, M, M.10.1 (7) Kieny, M, THP.32 (168) Kim, C, MP219 (46) Kim, H, THP.82 (I77) Kinder, B, WP.225 (147) King, N, THP.104 (I80); F.7.3 (212) Kingsley, L, M.6.2 (4); MR92 (25); MP.121 (30); WP.63 (120); TH.5.6 (157); THP.60 (173); E83 (213) Kinney-Thomas, E, THP.8 (164) Kinter, A, TP.106 (80) Kirk, R, WP.227 (I48) Kim, D, WP.47 (118) Kissinger, R, MP.107 (28) Kitchen, L, MP3 (10) Kitonyi, G, TP.249 (104) Kittur, D, WP.123 (130) Klanieki, J, MP35 (16) Klatzman, D, TH.9.6 (160) Klatzmann, D, M.10.1 (7); TP.105 (80) Klauber, M, TP.61 ( 72); WP.234 (149) Klauber, S, WP.234 (149) Klein, E, MP90 (25); TP.223 (99); WP.65 (121); WP.218 (146); THP.62 (173) Klein, H, TP.74 (74) Klein, M, MP49 (18); MRSO (18); TH.4.3 (155) Klein, N, TP.154 (88) Klein, R, M.3.4 (2); MP.155 (36); TP.143 (86); W.2.5 (106); WP.41 (117); WP.209 (145); TH.3.5 (I55); THP.197 (196); F.3.4 (208) Klein, S, WP.202 (144) Kleinman, P, THP.198 (I96) Kleinman, S, M.3.5 (2); MP232 (48); TP.234 (101); W.4.1 (107); W.4.2 (107); THP.246 (204) Klimas, N, MP.116 (29); WP.105 (127); THP.240 (203) Klimek, J, THP.220 (200) Klimenko, S, THP.40 (I70) Kline, A, TH.3.1 (154) Kline, M, TP.224 (99) Kline, R, THP.19 (166) Klock, J, WP.10 (112) Kloser, P, WP.60 (120) Kluge, J, MP.230 (48) Knight, S, THP.232 (202) Knowles, D, WP.230 (148) Knutsen, A, THP.127 (184) Koch, M, TP.24 (66); WR48 (118); WP.93 (125); THP.4 (164) Koch, S, THP.94 (179) Kochems, L, THP.182 (193) Kochen, J, THP.16 (166) Kock, M, THP.59 (173) Kodama, C, TP.173 (91) Koenig, B, TH.3.2 (154) Koenig, R, TP.187 (93) Koenig, S, MP.10 (11); MP.103 (27); T.9.3 (59); THP.109 (181) Koerper, M, MP.163 (37); TH.10.3 (161) Kohler, C, THP.164 (190) Kohmescher, R, T63 (56) Koito, A, W.3.2 (106) Kong, L, TH.2.3 (153) Kontio, S, TH.9.3 (160) Korkolainen, M, TH.9.3 (160) Kornfeld, H, WP.15 (112); TH.2.2 (153); THRS (164) Kosowski, S, WP.39 (116) Koss, L, TP.143 (86) Kost, T, TH.2.5 (154) Kotler, D, THP.148 (188) Kotval, 1, E86 (213) Kouri, Y, THP.138 (186) Kourouma, K, THP.75 (176) Kovacs, J, MR228 (48); T.8.2 (58); THP.226 (201 ) Kowalski, M, M.4.6 (3); T.4.3 (54) Krailo, M, THP.49 (171); THP.144 (187) Kréll, G, MR21 (13) Kramer, A, WP.132 (132) Krampf, W, THP.43 (170) Krasinski, K, W.5.2 (108); WP.72 (122); WP.141 (133); WP.142 (134); THP.103 (180); THP.145 (187) Kraus, B, TH.10.4 (161) Krause, P, E13 (206) Krebs, J, WP.181 (140) Kreek, M, THP.216 (199) Kreiss, J, TH.7.5 (158) Kreuz, W, TH.10.4 (161) Kreuzfelder, E, THP.131 (I85) Krilov, L, THP.122 (183) Kristal, A, WP.189 (I41) Krogh, G, MR93 (25); WP.83 (124) Krogsgaard, K, T35 (53); TP.41 (69); TP.81 ( 76) Krohn, K, M.10.4 (8); MP.17 (I3); MP.119 (30); W.3.6 (107); TH,9.1 (159); THP.35 (169) Kronawitter, U, WP.165 (I37) Krone, W, TP.100 (79) Krowka, J, T121 (82); T45 (54); TH.9.2 (I59) Krusr, B, TP.5 (63) Ktsanes, V, MP.184 (40) 226 Kuenssberg, B, WP.40 (117) Kufta, C, MP.159 (36) Kuhn, A, TP.183 (93); THP.173 (192) Kiihnel, H, WP.24 (114) Kumar, M, THP.155 (189) Kumar, P, TH.2.3 (153) Kumari, S, TP.94 (78) Kunches, L, MR242 (50); TP.47 (70) Kunze, R, TP.25 (66); THP.4 (164) Kuo, A, MP.95 (26) Kuritsky, J, W.4.4 (108) Kurowski, P, THP.234 (202) Kurth, R, TP.132 (84) Kushi, L, WP.198 (143 ) Kutzko, D, THP.192 (195) Kuzma, R, TH.4.2 (155) Kvinesdal, B, MP57 (I9) Kvitash, V, TP.200 (95) Kwoh, D, TP.9 (64) Kwok, S, WP.23 (114); THP.28 (168); F23 (207) Kyle, G, WP.189 (141) _L_ Lack, E, W.5.4 (109) Lafleur, F, TH.4.5 (156) L’age-Stehr, J, WP.48 (118); THP.59 (173) La Grenade, L, T48 (70) Lainson, F, MP245 (51); TR238 (102) Lamb, B, MP89 (25) Lamb, G, WP.210 (145) Lamberson, H, WP.226 (148); THP.246 (204); THP.247 (204) Lambert, T, M.11.5 (9) Lamon, K', MR240 (50) Lamotte, G, MP248 (51); WP.246 (151) Landay, A, WP.9 (111); THP.101 (180) Landers, S, WP.210 (I45) Landesman, S, TP.56 (71); TP.78 (75); TP.228 (100); WP.75 (122); WP.157 (136); WP.194 (142); WP.200 (143); TH.4.6 (156); TH.7.3 (158); THP.71 (175); THP.209 (198) Lane, C, WP.85 (124); WP.151 (135); THP.71 (175) Lane, H, MP.103 (27); MP.125 (31); MR228 (48); T.8.2 (58); T.9.3 (59); W.5.4 (109); TH.4.1 (155); THP.226 (201); E4.4 (209) Lang, W, M.3.2 (1) Lange, J, MP9 (11); MP.53 (19); TP.33 (68); TP.100 (79); THP.90 (178); THP.136 (186) Lange, M, TP.223 (99); WP.218 (146); THP.62 (I73); THP.231 (202) Lange, W, TP.54 (71); THP.95 (179) Langhoff, E, WP.101 (127) Langlade-Demoyen, P, WP.127 (131) Langlois, A, Tp.128 (83) Lansky, L, THP.193 (195) Lantos, G, W.5.3 (109) Laper, G, THP.201 (197) Larder, B, THP.22 (167) Laroche, A, M269 (21) Larouze, B, WP.32 (115) Larson, D, TP.248 (103) Laskin, O, TH.8.5 (I59) Lasky, L, M.4.4 (3); WP.12 (112); THP.20 (166) Latif, A, M.8.3 (6) Lau, A, WP.121 (130) Laurent, A, TP.5 (63) INDEX Laurian, Y, MR45 (I7) Lauritzen, E, MP57 (19) Laursen, I, MP.62 (20) Law, R, MR204 (44) Lawrence, A, M.6.4 (5) Lawrence, D, M.11.5 (9) Lawrence, J, MP.196 (42) Lawrence, R, W52 (108); WP.141 (133); THPJ45 (187) Lazarowicz, R, T.6.3 (56) Lazzarin, A, TP.230 (100); WP.89 (125); WP.151 (135); THP.89 (I78); THR118 (I83); THP.165 (191) ' Le, S, THP.39 (170) Learmont, J, WP.243 (150) LeBlanc, R, THP.96 (179) Lebow, L, TP.127 (83) Lebughe, I, TP.139 (85) Lecocq, J, THP.32 (168) Le Deist, F, TH.7.4 (158) Ledergerber, B, WP.81 (123) Lederman, M, MP.105 (27); TP.97 (78); F.1.3 (206) Lee, C, WP.137 (133) Lee, F, THP.61 (173) Lee, H, WP.170 (138) Lee, J, MP.176 (39); WP.155 (136) Lee, M, MES (11) Lee, N, TP.150 (87) Lee, S, TP.9O (77); TH.2.3 (153) Lee, T, T.3.l (53); WP.17 (113); WP.66 (121) Leece, B, TH.9.1 (I59) Leedom, J, MP.175 (39); T85 (58); TP.160 (89); WP.221 (147); TH.11.1 (161); THP.149 (188) Legg, H, WP.13 (112) Le Guern, A, TP.5 (63) Lehrman, S, T81 (58); THP.235 (202) Leibowitch, J, THP.106 (181) Leiderman, I, WP.145 (134) Leite Da Costa, J, THP.78 (176) Leitman, S, TP.74 (74) Lejeune, B, M.6.6 (5) Lekas, P, TP.115 (81) Lekatsas, A, TP.75 (75); WP.71 (122); THP.199 (196) Lelie, N, TP.92 (77); WP.73 (122); THP.90 (178) Lemp, G, T.49 (70); TP.51 (71); W46 (118) Lennette, E, MP.223 (47) Lenoir, G, TP.8 (63) Lenox, T, TP.154 (88) Leonard, G, F.2.5 (207); F.6.2 (21]) Leonard, J, MP.19 (I3); F.7.4 (212) Leonard, P, T.6.4 (56) Leonard, R, T165 (62) Leonard, T, THP.188 (194) Leoung, G, THP.154 (189); F.3.3 (208) Leport, C, MP.161 (37); WP.138 (133) Lerche, N, TP.6 (63) Lernestedt, J, THP.238 (203) Lesane, F, F.4.3 (209) Leslie, J, TP.185 (93) Lessner, L, TP.76 (75) Letvin, N, THP.104 (180); E73 (212) Leuther, M, MP4S (17); MP.87 (24); T.8.1 (58); TP.38 (68); TP.69 (74); WP.44 (117); F2.6 (207) Levacher, M, TP.126 (83) Levine, A, WP.146 (134); THP.49 (171); THP.144 (187) Levine, C, F.5.1 (210) Levine, J, TH.11.5 (162) Levine, P, M.11.4 (9); MP.86 (24); MR240 (50); TP.144 (86); F.1.3 (206) Levy, E, WP.198 (143) Levy, J, M.4.1 (2); MP.163 (37); T.121 (82); TP.130 (84); TP.187 (93); TP.44 (69); WP.7 (111); WP.13 (112); WP.14 (112); WP.80 (123); WP.107 (128); WP.111 (128); TH.10.3 (161 ); THP.47 (171); F95 (214) Lewis, D, WP.113 (129); THP.114 (182) Lewis, J, TP.236 (101) Li, P, TP.9O (77) Liautaud, B, MP.69 (21); MP.136 (32) Lieb, L, TP.91 (77); THP.51 (172) Lieb, S, W.2.3 (106); THP.83 (I77) Liesnard, C, MP.124 (30); MP.154 (35) Lifson, A, MP.83 (24); T.7.3 (57); TP.84 (76) Lifson, J, MP.12 (12); MP.130 (31); TRIM (81) Lightbourne, B, THP.243 (204) Lillehoj, E, THP.l7 (166) Lilley, P, TP.233 (101 ) Lillo, F, WP.151 (I35) Lin, R, WP.135 (132) Lin, T, THP.8 (164) Lindhardt, B, MR57 (19); MR62 (20); MR224 (47); TP.41 (69); TP.81 (76); WP.101 (127); WP.162 (I37) Lindner, W, F.4.2 (209) Lindstrom, E, MR3O (15) Linette, G, THP.109 (181) Link, R, TH.3.3 (154) Linke, M, MR219 (46) Linnan, M, THP.159 (I90) Liozner, A, MR97 (26) Lippa, A, M.5.6 (4) Livartowski, J, THP.76 (I76) Ljunggren, K, M106 (8) Llena, J, WP.154 (I36) Lloyd, A, THRIIS (182) Lode, H, WP.132 (132) Lodynski, A, THP.162 (190) Loeb, L, MP.169 (38) Loftus, J, WP.224 (147) Log, T, MR95 (26); WP.85 (124) Lombard-Cannan, M, WP.44 (117) Longworth, D, TP.162 (89) Looney, D, W.3.5 (107) Lopez, C, WP.109 (128) Los, A, TP.193 (94); THP.191 (195) Loskoski, S, MP229 (48); MR239 (50); WP.233 (149) Loureiro, C, THP.49 (171); THP.144 (187) Lourenco, M, THP.88 (178) Loveless, M, THP.128 (184) Low, B, WP.50 (118) Lowe, G, T2241 (102); WP.238 (150); THP.244 (204) Lowen, N, TP.245 (103) Lowenstein, W, THP.239 (203 ) Lowenstine, L, TP.6 (63) Lowy, M, TP.240 (102) Lu, H, MP.84 (24) Lubaki, M, T76 (57) Lubaki, N, E9.6 (214) 227 Luban, N, WP.239 (150); THP.242 (203) Luby, J, THP.229 (201) Lucas, C, TP.246 (103) Lucchini, A, MR4] (I7) Luciw, P, M.9.1 (6); MR26 (14); TP.36 (68) Ludlam, C, MR245 (51); TP.124 (83); TP.238 (102); WP.102 (127) Liier, W, TP.157 (88) Luft, B, TH.8.6 (159) Lugo, S, MP.134 (32) Lui, K, TH.10.1 (160) Lukehart, S, THP.68 (174) Lunardi-Iskandar, Y, MP.112 (28); F.4.6 (209); E9.4 (214) Lundin, K, MP.39 (I6) Luney, C, TP.54 (71 ); THP.95 (I79) Lurhuma, Z, T165 (62) Liithy, R, WP.81 (123) Luzia, L, THP.78 (I76) Lwegaba, A, TH.5.4 (157) Lyerly, H, T.9.4 (59); TP.128 (83) Lyndall, P, TP.85 (76) Lynn, D, WP.33 (115) Lyons, C, WP.75 (122); WP.200 (143) Lyons, P, WR90 (125) Lyons, S, MP.40 (16); MR58 (I9) Lyter, D, M.6.2 (4); MP.121 (30); WP.67 (121); WP.106 (128); THP.64 (174); F.8.3 (213) _M_ Maayan, S, MR51 (18) MacDonald, K, MP.193 (42); T75 (57); WP.235 (149); THP.176 (I92) Macher, A, M.11.6 (9); TR169 (90); WP.168 (138); WP.170 (I38) Macik, G, MR78 (23) Mack, D, F.2.3 (207) Mackay, I, WP.92 (125 ) Macks, J, THP.203 (197) Madden, D, THP.108 (181) Maddon, P, M.4.3 (3) Madhok, R, TP.241 (102); WP.238 (150); THP.244 (204) Madjar, J, TP.37 (68); THP.33 (169) Maesaka, J, TP.148 (87) Maganu, E, MR60 (20) Maguire, B, WP.74 (122); THP.213 (199) Maha, M, THP.235 (202) Mahabir, B, TP.96 (78); F.6.4 (211) Mahloane, L, MR60 (20) Mahon, R, MP.175 (39) Mahony, K, THP.182 (193) Maillard, M, WP.89 (125) Maino, V, TH.9.2 (159) Maizel, J, THP.39 (170) Major, E, MP.159 (36) Makuch, R, TP.38 (68) Makuwa, M, TP.52 (71) Malavade, V, WP.236 (I49) Males, B, MR238 (49) Malkovsky, M, M.4.3 (3); MP.122 (30); TP.3 (63) Malone, G, TH.10.5 (161) Manabe, S, MR235 (49) Manak, M, WP.21 (113); WP.22 (114) Mandel, J, TP.203 (96); THP.218 (199) Mandelli, F, THP.248 (204) Manikar, S, WP.240 (150) INDEX Mankikar, S, TP.243 (103) Mann, D, T.9.2 (59); E12 (206); E43 (209) Mann, J, M.3.6 (2); M.8.5 (6); MP6] (20); MP.73 (22); T13 (52); W.4.6 (108); WP.55 (119); WP.84 (124); WP.136 (133); TH.7.6 (158); THP.55 (172); E96 (214) Mannella, E, WP.122 (130); WP.248 (151) Mannucci, P, THP.248 (204) Manoff, S, TP.42 (69); TH.7.1 (157) Mansell, P, T.8.5 (58); TP.134 (84); TP.218 (98); THP.135 (186); THP.234 (202); THP.236 (202) Mantell, J, THP.182 (193) Mantovani, A, THP.118 (183) Manyeneng, W, MR60 (20) Marcel, A, TP.228 (100); WP.75 (122) Marche, C, MP.161 (37); WP.160 (137); THP.141 (187); THP.161 (190) Marcus, R, THP.223 (200) Marcus, S, TP.227 (100) Marechal, V, THP.37 (169) Marennikova, S, THP.40 (170) Margolick, J, WP.117 (129) Margolis, I, TP.87 (77) Mariani, G, THP.248 (204) Marin-Garcia, J, MP.170 (38); TP.170 (90) Marion, R, WP.153 (135) Markham, P, MP.34 (15); TP.19 (65); TP.20 (65) Marlene, M, THP.78 (176) Marlink, R, TH.5.1 (156); THP.7 (I64) Marmor, M, MP.201 (43); TP.69 (74); WP.72 (122); THP.69 (175); THP.178 (193) Marquis, J, W.5.1 (108) Marquis, L, WP.53 (119) Marsh, J, MP.130 (31) Marsh, M, MPZO (13) Marshall, D, WP.156 (136) Martin, J, TP.65 (73); WP.177 (139); THP.79 (176); THP.217 (199) Martin, L, MR229 (48); MR239 (50); TP.109 (80); WP.19 (113); WP.233 (149); THP.113 (182) Martin, M, M.4.5 (3); M.9.4 (7); MP.l9 (13); W.3.4 (107); F.7.4 (212) Martinez-Mala, O, THP.121 (183) Martini, E, THP.132 (I85) Martini, M, THP.168 (I91) Martiniwitz, U, TH.10.5 (161) Martuzzi, M, TP.113 (81) Marx, P, MP.230 (48) Mascaretti, L, MP.249 (51) Mascola, L, THP.51 (172) Masdeu, J, WP.154 (136) Masinovsky, R, MP35 (16) Masison, V, THU (65 ) Maskill, W, TP.246 (103); THP.31 (168) Maslansky, R, MP.201 (43) Mason, P, WP.115 (129) Massari, V, TP.180 (92) Massey, J, TP.57 (72) Massuet, L, WP.249 (I51) Mastroianni, P, THP.182 (193) Mastrucci, M, WP.166 (138); THP.91 (178); THP.167 (191) Masur, H, MP228 (48); T82 (58); W54 (109); TH.4.1 (I55); THP.226 (201) Matheron, S, MP.148 (34); TP.27 (67); TP.165 (90); TP.216 (98); THP.161 (190); THP.169 (191) Mathez, D, THP.106 (181) Mathiot, C, MP164 (37); TP.79 (75) Matsevich, G, THP.40 (170) Matsukura, M, T.4.1 (54); T.4.4 (54) Matsushita, S, T.4.1 (54); W32 (106) Matthews, T, M.10.3 (8); MP36 (16); MP.78 (23); T.9.4 (59); T.16.4 (62); TP.128 (83); WP.33 (115); THP.35 (169) Mattinen, S, M.10.4 (8) Matts, L, THP.82 (177) Matuschke, A, MP.166 (37) Matzk, D, TP.159 (89) Matzke, D, WP.140 (133) Maude, D, TP.143 (86); W25 (106) Mauge, C, THP.198 (196) Mauser-Bunschoten, E, M115 (9) Mawle, A, TP.108 (80); WP.99 (126) May, T, MP.118 (29); THP.164 (190) Mayaud, C, MP.123 (30); MP.158 (36); WP.164 (137) Mayaux, M, TH.7.4 (158) Mayer, K, MP52 (18); MP89 (25); MR244 (50); TP.64 (73); TP.174 (91); WP.172 (139) Mayers, D, TP.135 (85) Mayers, M, TP.67 (73); TH.7.2 (I57); THP.197 (196) Mayr, C, T46 (70) Mazeron, M, TP.142 (86) Mbayo, K, T.16.5 (62) Mbena, E, TP.86 (76) Mbesa, H, MR61 (20) M‘Boup, S, THP.7 (164); F.6.6 (211) McAllister, D, THP.51 (172) McArthur, J, MP66 (21); MP.142 (33); TP.140 (85) McAuliffe, W, MP.181 (40) McBride, L, MR55 (19) McCabe, D, THP.26 (167) McCalla, S, TP.78 (75) McCallum, D, M2212 (45) McCarthy, P, TH.3.4 (155) McCarthy, S, F.4.4 (209) McCartney-Francis, N, TP.133 (84) McClure, H, MP.27 (14), E72 (212) McClure, J, MP35 (16), T95 (59), TP.32 (67) McClure, M, M220 (13), TP.4 (63) ' McCluskey, T, THP.183 ( 194) McCormick, J, MP72 (22); TP.145 (86); WP.43 (117) McCrory, L, THP.234 (202) McCusker, J, TP.64 ( 73); TP.174 (91); WP.172 (I39) McCutchan, A, WP.234 (149) McCutchan, J, MP.l45 (34); MP.200 (43); TP.61 (72); TP.158 (88) McDonald, J, WP.215 (146) McDonald, L, WP.40 (117) McDougal, J, MR127 (31); TP.108 (80); TP.109 (80); WP.99 (126); THP.100 (180) McEvoy, M, MP.67 (21) McFarlane, R, MP.l97 (43) McGhee, B, MR238 (49) McGillivray, G, MR58 (19) McGrath, H, TP.188 (93) McGrath, K, TP.246 (103) McGrath, M, MP.130 (31); TP.115 (81); F.9.3 (214) 228 McGuire, G, TH.11.6 (162) McHenry, M, TP.162 (89) McKinley, G, TP.223 (99); WP218 (I46); THP.62 (173) McKinney, C, THP.182 (193) McKusick, L, WP.184 (141); WP.186 (141); WP.232 (149); F82 (213) McLane, M, MR29 (15) McLees, B, TH.4.2 (155) McLeod, A, MP.111 (28); TP.99 (79) McLeod, W, M33 (2) McMahon, C, THP.247 (204) McManus, T, THP.137 (186) McMaster, P, TH.11.2 (161) McMeeking, A, WP.147 (I34) McNally, L, TH.11.6 (162) McNamara, G, WP.225 (147) McNeil, J, TP.166 (90); TP.237 (102) McNulty, W, WP.34 (116) McPhee, D, TRIS (65); WP.6 (111) Medina, I, W.5.5 (109); E31 (208); F.3.3 (208) Megill, M, WP.205 (144); THP.226 (201 ) Meidema, F, THP.126 (184) Meigel, W, TP.155 (88) Meignan, M, WP.164 (137) Melbye, M, MR65 (21 ) Melcher, G, T.7.2 (57) Melica, G, TP.83 (76) Mellert, W, MP.104 (27) Mellor, A, M.4.3 (3) Melpolder, J, TP.74 (74) Meltzer, M, E74 (212) Mendelson, J, TP.170 ( 90) Mendes, N, THP.85 (177) Mendez, H, WP.157 (I36); TH.7.3 (158); THP.71 (175); THP.158 (189); THP.209 (198) Meon, M, TP.189 (94) Merigan, T, THP.125 (184) Merlin, M, M.8.1 (5); WP.77 (123); WR78 (123) Meropol, N, E13 (206) Merritt, R, MR190 (41) Mertens, S, TP.28 (67) Mertz, G, THP.186 (194) Mervis, R, THP.17 (I66) Mesa-Tejadar, R, WP.154 (136) Mesagno, F, T102 (60); TP.171 (91) Mess, T, TP.219 (99); WP.217 (I46) Messiah, A, MP.79 (23) Metellus, G, THP.45 (171); THP.83 (177) Metroka, C, WP.220 (I47); THP.230 (201 ); THP.231 (202) Mettetal, J, MP.79 (23) Meyer, R, THP.150 (188) Mezzaroma, I, TP.117 (82) Mhalu, F, TP.86 (76) Mian, A, WP.1 (110) Michaeli, D, MR51 (18) Michaelis, B, WP.13 (112) Michel, F, WP.127 (131) Michon, C, MP.148 (34); MP.161 (37); THP.169 (191) Miedema, F, TP.33 (68); WP.36 (116); WP.125 (I31); THP.90 (178); THP.136 (186) Miehakanda, J, TP.52 (71) Mielke, C, WP.10 (112) Mijch, A, TP.246 (103) Milberg, J, TP.42 (69); THP.67 (174) INDEX Mildvan, D, TR69 (74); W5.6 (109) Miles, S, TR227 (100); THR206 (197) Miller, B, THR66 (174) Miller, D, T.6.4 (56); TR201 (96) Miller, E, MR76 (22); TR233 (101); TR39 (69); WR137 (133) Miller, J, WR88 (125) Miller, K, TR168 (90) Miller, L, TR186 (93); TR190 (94); THR177 (193) Miller, R, MR76 (22); MR81 (23); T50 (70) Mills, J, MR221 (47); T121 (82); W5.5 (109); WR231 (148); F.3.3 (208); E93 (214) Mimms, L, MR244 (50); TR235 (101) Mingle, J, MR94 (25); THR65 (174) Minkoff, H, TR78 (75); WR157 (136); TH.7.3 (158) Minnefor, A, TP.226 (100) Minnick, S, MR209 (45) Miotti, P, WR116 (129) Miraglia, E, TR244 (103) Mitchell, M, THR175 (I92) Mitchell, N, ”E61 (56) Mitchell, S, THR28 (168) Mitchell, W MR5 (11); MR6 (11); TR98 (78); WR97 (126); THRl (163) Mitsuya, H, MR103 (27); T.4.1 (54); T.4.4 (54); THR10 (165) Mitsuyasu, R, MR109 (28); MR222 (47); TR127 (83); TR227 (100); WR103 (127); THR121 (183); THR232 (202) Mizel, D, TR133 (84) Mizuma, H, TR110 (80) Mizuochi, T, WR100 (127) Moas, C, THR143 (187) Moberg, L, MR93 (25); WR83 (124); THR130 (185) Moehring, R, TR183 (93); THR173 (192) Moelling, K, THR36 (169) Moerkerk, H, MR178 (39) Mok, J, MR47 (18); TR205 (96); WR204 (144) Moller, J, TR123 (83) Monplaisir, N, MR96 (26) Monroe, J, TP.8 (63) Montagna, R, WR23 (114) Montagnier, J, TH.9.6 (160) Montagnier, L, M.10.1 (7); M.10.5 (8); MR2 (10); MR80 (23); TP.5 (63); TH.1.1 (153); TH.2.1 (I53); THR32 (168); E71 (212) Montefiori, D, MP5 (11); MR6 (11); TP.98 (78); WR97 (126); THRl (163) Montgomery, S, T.10.6 (60) Moody, D, MR120 (30); WR111 (128); E95 (214) Moon, M, TR64 (73) Moore, J, TR36 (68); WR29 (115) Moore, P, MR211 (45) Moore, T, W5.2 (108); WR141 (133); THR103 (180) Moran, P, T95 (59) Morfeldt-Mé’mnson, L, WR83 (124); THR13 (165); THR238 (203) Morin, S, WR184 (141); WR186 (141); E8.2 (213) Morisky, D, WR189 (141) Morlet, A, WR188 (141); THR222 (200) Moroni, M, WR151 (135); THR165 (191) Moroso, G, THP.209 (198) Morris, J, TP.246 (103) Morrisey, E, WP.44 (117) Morrison, C, WR172 (I39); TH.3.4 (155) Morrison, M, WR40 (117) Morrison, S, MR162 (37); MR170 (38); TR215 (98); TR226 (100); W5.1 (108) Morrow, J, TR130 (84) Morse, D, TR177 (92); WR61 (120); WR74 (122); THR70 (175) Mortimer, P, MR9 (II) Morton, W, MR15 (12) Mosca, J, WR38 (116) Moser, S, MR180 (40) Mosimann, J, MR46 (17) Moskovitz, B, TP.222 (99) Mosley, J, MR84 (24); TH.10.2 (160) Moss, A, MR87 (24); TR53 (71); WR199 (143); THR43 (I70); THR47 (171); F.1.4 (206); F.1.5 (206) Moss, B, T.9.1 (59); T92 (59); T.9.3 (59); W3.1 (106) Motley, L, MR248 (51); WR246 (151) Motyl, M, MR155 (36) Moulton, J, WR199 (I43); WR201 (I43) Mounier, M, E25 (207) Mouradian, J, THP.230 (201) Moynihan, R, MR197 (43) Moyorga, R, WR160 (I37) Mozzi, F, MR249 (51) M’Pania, M, WR136 (133) M’Pele, P, WP.79 (123) Muchinik, G, MR134 (32) Mucke, L, MR143 (34) Muesing, M, TR31 (67) Mulder, C, TP.8 (63) Mulhall, B, WR92 (125) Muller, J, THR132 (185) Mfiller, W MR1 (10) Mullins, J, WR15 (112); TH.2.2 (153); THRS (164) Mundon, F, TP.248 (103); E65 (211) Mundy, T, MR169 (38) Munjal, D, WR247 (151 ) Munn, R, E75 (212) Munoz, A, MR92 (25); TR73 (74); WP.64 (121); THR119 (183) Munoz, L, TR102 (79) Murali, M, TP.228 (100) Murhpey-Corb, M, THR113 (182) Murithii, J, WRSO (118) Murphey-Corb, M, THR21 (167) Murphy, D, MR203 (44) Murphy, E, T48 (70) Murphy, V, WP.76 (123); THR73 (175) Murphy-Corb, M, WR19 (113) Murray, C, E12 (206) Murray, P, WR143 (134); WR144 (134); THR142 (187) Mussa, M, WR136 (133) Mutinelli, M, THR16S (191) Mwendapole, R, MR77 (23 ) Myers, C, WR223 (I47) Myers, G, MR14 (12) Myers, P, TR208 (97) Myrtveit, M, THR59 (173) _N- Nachman, S, TR55 (71) Nadelman, R, TP.211 (97) 229 Nagashima, K, MR13 (12) Nagel, J, WR119 (130); WR123 (130) Nahmias, A, THR61 (173) Nair, P, MR85 (24) Najera, R, TR102 (79) Nakamura, G, M.4.4 (3); WR12 (112) Nakamura, S, MR32 (I5); TR125 (83); WP.5 (111) Nara, P, MR31 (15); WR3 (110); E76 (212) Narvanen, A, TH.9.3 (I60) Nasca, P, WR68 (121) Nason, M, W43 (108) Nath, N, MR234 (49) Nay, K, TR141 (86) Naylor, C, THR107 (181 ) Naylor, P, TR134 (84); WR18 (113); THR107 (181) Ndinya-Achola, J, M.8.4 (6); MR91 (25); WRSO (118); TH.5.5 (I57); TH.7.5 (158) Ndoko, K, TR139 (85) Ndongala, L, THR18 (166) Neequaye, A, MR94 (25 ); THR65 (174) Neff, S, THR233 (202) Negre, M, T103 (60) Negri, C, TP.230 (100) Neil, G, MR137 (33) Neisson-Vemant, C, MR96 (26) Nelson, A, WR168 (138); TH.7.6 (158) Nelson, K, WR116 (129); WR208 (145) Nelson, L, WR53 (119) Nelson, W, TR207 (97) Nencioni, L, THR118 (183) Neshin, S, MR210 (45 ) Nettey, V, MR94 (25); THR65 (174) Neumeyer, D, TR30 (67) Newlin, B, WR219 (146) Newman, C, MR10 (11) Newstetter, A, MR75 (22) Ng, V, MR130 (31) N’Galy, B, MR61 (20); WR136 (133) Ngaly, B, M.3.6 (2) Ngovan, P, T.5.4 (55) Ngugi, E, M.8.4 (6); TH.5.5 (157) Nguyen-Dinh, P, M.8.5 (6); MR73 (22); TR139 (85) Nicholas, H, T.6.4 (56) Nicholas, S, TH.11.3 (162) Nichols, M, TR198 (95) Nicholson, J, MR127 (31 ); TR108 (80); THRIOO (180) Nickens, N, E5.6 (210) Nielsen, C, MR224 (47); T.3.5 (53) Nielsen, J, T35 (53); TR81 (76) Nielsen, M, T75 (57) Nienaltow, M, MRISO (35) Niese, D, THR168 (191) Nigra, E, MR41 (I7) Nikora, B, T.5.3 (55); WR54 (119) Niland, J, MR84 (24); MR88 (24) Nishanian, P, T32 (53); T.9.6 (59) Nixon, A, MR204 (44) Noa, M, WR190 (142) Noche, L, WP.78 (123) Noel, L, TR80 (75) Norcross, M, TR16 (65) Norman, G, WR146 (134) Norman, S, TR141 (86) INDEX Norrby, E, M.2.2 (1);THP.29 (168) Norris, H, MP.199 (43) Novick, D, THP.216 (199) Nseka, K, W.4.6 (108) Nugeyre, M, F.9.4 (214) Nunes, A, THP.85 (177) Nunes, W, WP.25 (114) Nyamuryekunge, K, TP.86 (76) Nyanjom, D, THP.179 (193) Nyarango, P, TP.41 (69) Nye, K, TP.111 (81) . Nygren, A, MP30 (15); MP39 (16) Nzila, N, THP.159 (190) Nzilambi, N, TP.145 (86); W.4.6 (108); WP.43 (117); TH.7.6 (I58) -0— O’Brien, T, TP.236 (101); TP.242 (102); WP.226 (148) Ochs, H, MP.15 (12) Ocuno, L, WP.30 (115) Odajnyk, C, WP.230 (148) Odaka, N, WP.66 (121); WP.116 (129); THP.119 (183) Odete Santos Ferreira, M, THP.88 (178) O’Donnell, J, MR221 (47) O’Donnell, M, TP.173 (91) O’Donnell, R, TP.76 (75); WP.71 (122); WP.155 (I36); THP.199 (196) O’Dowd, M, WP.209 (145) Odum, N, TP.123 (83) Oette, D, MP222 (47) Officer, J , MR204 (44) Offutt, S, TP.211 (97) Ogg, P, THP.193 (195) Ognibene, F, W.5.4 (109) O’Hearn, P, WP.196 (143) Ohta, Y, MP28 (14) Ojo-Amaize, E, T.9.6 (59) Oksenhendler, E, WP.228 (148) O’Leary, T, M.11.6 (9); THP.30 (I68) Oleske, J, MP.162 (37); MP.170 (38); MP.213 (45); TP.170 (90); TP.215 (98); TP.226 (100); W.5.1 (108); WP.169 (138); WP.213 (145); THP.212 (198) Oleszko, W, THP.243 (204) Oliva, G, T.6.5 (56) Olivier, R, M.10.1 (7) Ollivier-Henry, F, E2.1 (207) O’Malley, P, M.3.1 (1); THP.207 (198); E81 (213) Ong, K, TP.223 (99); WP.65 (121); WP.218 (146) Operskalski, E, TP.60 (72) Oppermann, A, WP.70 (122) Orbe, M, WP.227 (148) O’Reilly, K, WP.182 (140) Orenstein, J, TP.106 (80) Orgad, S, TH.10.5 (I61) Orkin, J, MR27 (14); F.7.2 (212) Ornitz, D, T.5.1 (55); WP.148 (135); THR153 (189) Oroszlan, S, M.9.3 (7); TR21 (66) O’Rourke, M, TP.207 (97) Osborne, M, MP.108 (28); MP.109 (28) Osei, W, MR60 (20) Osei-Kwasi, M, MP94 (25); THP.65 (174) O’Shaughnessy, M, MP.16 (12); W34 (107); WP.215 (146); THP.96 (179) Osmond, D, MP87 (24); TP.53 (71); WP.199 (143); THP.43 (170); THP.47 (I71); F.1.5 (206) Ostchega, Y, THR219 (200) Ostergaard, L, W1.2 (105) Osterholm, M, MP.193 (42); T.7.5 (57); WP.235 (149); THP.176 (192) Ostrove, J, MP.19 (13); MP22 (I3) Ostrow, D., MP.142 (33); T.10.6 (60); TH.5.6 (157); THP.80, (176); E8.4 (213) O’Sullivan, M, THP.231 (202) Ottomanelli, G, WP.227 (148); THP.124 (184) Cu, C, THP.28 (168) Outuki, N, WP.30 (115) Oxtoby, M, TH.7.1 (I57) Ozel, M, TP.24 (66) _P_ Padian, N, WP.53 (119); THP.48 (I71) Paganelli, R, TP.117 (82) Pahwa, R, F.4.1 (209) Pahwa, S, F.4.1 (209) Palangie, A, MP98 (26) Pallis, K, MP248 (51); WP.246 (151) Palmer, C, THP.162 (190) Pamphile, M, M.8.6 (6) Panavelil, T, W.3.6 (107) Pantarotto, F, TP.83 ( 76) Pape, J, M.8.6 (6); MP.68 (21); MR69 (21); MP.136 (32); TP.43 (69) Papouin, G, TP.95 (78) Papsidero, L, WP.23 (114) Paradis, T, T.9.1 (59); WP.104 (127) Parekh, B, MP248 (51) Parenti, D, TP.220 (99) Parikh, K, THP.147 (188); THP.157 (189) Parker, D, T.3.4 (53) Parkin, J, TP.111 (81); WP.245 (I51); TP.111 (81); TH.8.3 (159) Parks, E, MP38 (16); TP.38 (68); W33 (107); WP.11 (112); F.2.2 (207) Parks, P, TP.172 (91 ) Parks, W, MR38 (16); T.8.1 (58); TP.38 (68); TP.136 (85); W.3.3 (107); WP.11 (112); WP.166 (I38); THP.91 (I78); F22 (207) Parquin, F, MP.158 (36) Parr, D, T.6.4 (56) Parravicini, C, WP.124 (I31) Parry, J, MR9 (11) Partanen, P, TH.9.3 (160) Pasechnik, V, WP.98 (126) Pasquali, M, WP.250 (152) Pastore, L, TP.169 (90) Patarca, R, T162 (62) Patel, P, MP.115 (29) Patronik, S, THP.220 (200) Patten, E, MP.128 (31) Patzer, E, WP.12 (112) Paul, D, MR45 (17); MP.S3 (19); TP.225 (100); W.5.2 (108); WP.9 (111); THP.101 (180); THP.103 (180); THP.106 (181) Paul, L, TP.235 (101) Paul, N, WP.108 (128) Pauli, G, TP.24 (66) Paulson, Y, THP.151 (188) Pauwels, R, MP4 (10); T42 (54); TP.1 (62); TP.23 (66) Pawel, B, MP.170 (38) 230 Payte, J, TP.54 (71 ); THP.95 (179) Pearson, A, TP.250 (104); WP.94 (126) Peckham, C, MR47 (18) Pedersen, C, MR224 (47); T35 (53); TP.81 (76) Pedersen, N, TP.54 (71); E75 (212) Pederson, C, TP.123 (83) Pedro, M, THP.88 (I78) Peixinho, Z, THP.85 (177) Pekovic, D, MP.102 (27) Pelissier, J, T.5.6 (55) Pellet, P, MP.Z6 (I4) Penhallow, R, MP.12 (12) Penley, K, TP.70 (74); TP.71 (74); THP.58 (173) Penny, R, MP63 (20); TP.101 (79); WP86 (124) Pepkowitz, S, MR169 (38) Pepose, J, MP.10 (11) Perdices, M, WP.149 (135) Perez, E, THP.171 (192) Perez, G, THP.171 (192) Perez Garcia, R, MP.167 (38) Perkins, H, M.3.2 (1); M.3.5 (2); W.4.3 (108); WP.237 (I49); THP.53 (I72) Perkins, J, THP.194 (195); THPZOO (196) Perno, C, THP.10 (165) Perol, Y, MP.149 (35); TP.142 (86) Perronne, C, WR138 (133) Perry, J, TP.206 (96) Perry, S, MP.195 (42) Pert, C, M.5.1 (3) Perucci, C, WP.248 (151) Perumal, V, WP.69 (121); HP.147 (I88); THP.157 (I89) Pesce, A, T.10.3 (60) Petat, E, WP.27 (114) Peterlin, B, M.9.1 (6) Peterman, T, M.3.4 (2); WP.42 (117); TH.10.1 (160) Peters, S, MP.18 (13) Petersen, C, TH.8.4 (159) Petersen, E, MP.225 (47) Petersen, H, MP62 (20); TP.41 (69) Petersen, L, THP.44 (I70) Petersen, V, MP223 (47) Peterson, K, THP.58 (173) Petillo, J, MR24O (50) Petit, A, WP.125 (I31); THP.126 (184) Petrella, R, TP.131 (84); WP.114 (129); THP.117 (183) Petrov, R, MR97 (26) Petrus, D, THP.66 (174) Petteway, S, M103 (8); MP36 (I6); T.3.1 (53); TP.35 (68); TP.85 (76); WP.226 (148); TH.9.1 (I59); THP.26 (167); THP.27 (I68) Peutherer, J, MP.245 (51 ); TP.124 (83); TP.238 (102); WP.102 (127) Pezeshkpour, G, MP.144 (34); TP.151 (87) Pfenninger, L, TP.22 (66) Phair, J, MP.142 (33); MP92 (25); T.10.6 (60); T.3.1 (53); T32 (53); T.3.6 (53); THP.64 (174); TP.72 (74); TP.73 (74); WP.67 (121); WP.117 (129); WP.129 (131) Phelan, J, TH.3.5 (155) Phillips, A, TH.4.3 (155) Philpott, K, M.4.3 (3) Pialoux, G, MP.189 (41); TP.126 (83) Piaua, P, WP.106 (127) Picard, C, WP.164 (I37); THP.123 (184) INDEX Piccardo, P, THP.108 (181) Picchio, G, MP.134 (32) Pickering, J, TP.91 (77) Pickles, H, TP.194 (94) Pieper, A, TP.14 (64) Pics, C, MP.75 (22); T.6.5 (56) Pignon, J, WP.138 (133) Piland, T, T49 (70) Pinching, A, TP.111 (81); TH.4.4 (156); TH.8.3 (159) Pindborg, J, MP.207 (44); TP.161 (89) Pindyck, J, MR247 (51 ); TP.240 (102); TP.247 (103); WP.236 (149) Pinsky, P, T52 (55) Pinter, A, TP.110 (80) Piot, D, MP217 (46) Piot, P, M23 (1); M.8.4 (6); MP82 (23); MR91 (25); TP.63 (73); TP.139 (85); TP.145 (86); W24 (106); WP.43 (117); WP.51 (118); THP.139 (186); THP.227 (201) Pitchenik, A, TP.168 (90); THP.143 (187) Pitha, P, WP.38 (116) Pitlik, S, MP5} (18) Pizzuti, D, TH.4.6 (156) Plata, F, WP.127 (I31); THP.32 (168) Plescia, O, MR226 (47) Plummer, F, M.8.4 (6); MP9] (25); TH.5.5 (157); TH.7.5 (158); THP.68 (174) Podapati, N, THP.147 (188) Pohle, H, TP.157 (88) Poiesz, B, WP.23 (114); WP.226 (148); F23 (207) Polesky, H, MR237 (49); WP.235 (149) Poli, F, MP.249 (51) Poli, G, TP.106 (80); THP.118 (183) Polis, M, T32 (53) Polk, B, MP.66 (21); MP92 (25); T32 (53); TP.73 (74); WP.66 (121); WP.116 (129); WP.129 (131); F.8.4 (213) Polk, F, WP.241 (150); THP.119 (183) Pollak, M, M.5.4 (4); M.6.6 (5) Pollard, R, TP.159 (89); WP.140 (I33) Pollet, S, THP.215 (199) Pollowy-Domek, M, WP.44 (117) Polmar, S, WP.108 (128) Poncin, M, THP.61 (173) Pontani, D, MP.226 (47) Poole, L, WP.57 (119) Popescu, M, THP.166 (191) Popovic, M, MP.104 (27); MP.131 (32); T120 (82); F43 (209); E9.1 (214) Popovsky, M, THP.246 (204) Porwit, A, WP.128 (131) Poser, S, TP.157 (88) Potasman, I, TH.8.6 (159) Pottage, J, TP.225 (100) Pottathil, R, MP238 (49) Pottenger, L, TP.212 (97) Potz, J, M.4.6 (3); THP.6 (164) Poulsen, A, MR57 (19); MP224 (47) Poust, B, TH.11.5 (162) Powell, D, T.9.3 (59) Powell, K, THP.22 (167) Preble, O, MR7O (21) Price, R, T.5.1 (55); WP.148 (135); THP.153 (189) Prieto, V, MP.173 (39) Primm, B, MR203 (44); TP.54 (71); THP.95 (179) Pristera, R, THP.89 (178) Prodouz, K, T2245 (103) Proudfoot, A, T.6.1 (56) Prusoff, W, THP.8 (164) Przedborski, S, MP.154 (35) Puissant, F, WP.80 (123) Pulsatelli, L, TP.113 (81 ) Purifoy, D, THP.22 (167) Purvis, S, TP.97 (78) Putnam, D, WP.61 (120) Putney, S, M.10.3 (8); MP.17 (13); T.16.4 (62); TP.132 (84); WP.33 (115); THP.35 (169) Pyle, S, TP.10 (64); TP.13 (64); F.7.6 (212) Quackenbush, M, THP.187 (194) Quader, A, THP.216 (I99) Quadland, M, WP.183 (140) Quattara, A, TP.153 (88) Quinn, T, M.3.6 (2); M.8.5 (6); MP.10 (11); WP.84 (124); TH.3.6 (155); TH.7.5 (I58); THP.18 (166); THP.19 (166); THP.63 (174); THP.68 (174); THP.139 (186); THP.159 (19o),- F.9.6 (214) Quinnan, G, MP.125 (31); T92 (59); THP.120 (183); THP.122 (183) Qureshi, N, THP.112 (182) _R_ Rabin, D, MP.188 (41) Rabin, H, TH.9.1 (159) Rabin, L, TP.114 (81 ) Rabkin, B, T.10.5 (60) Rabkin, C, TP.247 (103) Rabson, A, MP.19 (13); MP22 (13) Rademaker, M, MR67 (21 ) Raevsky, C, TP.239 (102); TP.58 (72); WP.176 (139); THP.174 (192) Raghunath, J, THP.216 (199) Ragni, M, TP.236 (101) Ragone, V, THP.124 (184); WP.227 (148) Rahman, R, TP.21 (66) Rai, A, TP.94 (78) Rainer, C, MP.130 (31); THP.154 (189) Raise, E, TP.112 (81); TP.113 (81) Raj, N, WP.38 (116) Ram Ayyar, D, MP.139 (33) Ramey, W, THP.62 (173) Ramsey, K, MP.128 (31) Rance, N, TP.140 (85) Ranki, A, M.10.4 (8); MP.17 (13); MP.119 (30); W36 (107); TH.9.1 (159) Rao, N, TP.160 (89) Rao, T, MP.157 (36) Raphael, B, WP.230 (148) Raphael, M, MP.123 (30) Rappersberger, K, TP.107 (80) Rappocciolo, G, WP.106 (128) Rarick, M, THP.49 (171); THP.144 (I87) Rasheed, S, T.4.6 (54); WP.146 (I34); THP.49 (171) Raska, K, THP.82 (177) Ratner, L, M95 (7); WP.108 (128) Raum, M, THP.17 (166) Rautmann, G, THP.32 (168) Rawlinson, V, MP.233 (49) Rawson, D, WP.214 (146) Rayner, M, TP.35 (68) 231 Razin, A, WP.209 (145) Read, S, MP49 (I8); MPSO (18); TP.224 (99); WP.121 (130); TH.4.3 (155); TH.8.1 (158) Reagan, K, TP.14 (64); WP.4 (111) Reaman, G, WP.239 (150); THP.242 (203) Reddy, M, MP90 (25) Redfield, R, M.11.1 (8); T71 (57); W.3.5 (107); WP.17 (113); WP.66 (121); WP.110 (128); THP.99 (180); THP.105 (181); TP.166 (90); F.1.1 (206) Reed, C, WP.29 (115) Reed, D, MR36 (16); TP.85 (76); THP.26 (167) Reesink, H, WP.73 (122) Reeves, J, TP.45 (70) Reff, V, TP.77 (75) Regnier, B, THP.141 (I87) Regueiro, J, THP.116 (182) Rehm, S, TP.162 (89); WP.222 (147) Reibnegger, G, MR99 (26) Reid, B, MP.42 (17) Reife, R, WP.109 (128); THP.228 (201 ) Reimer, C, MP.127 (31 ) Reinarz, J, MP.128 (31 ) Reitz, M, MP25 (14); MP33 (15); T.4.1 (54) Rekart, M, TP.192 (94); WP.191 (142); THP.189 (195) Rekosh, D, MP30 (15) Remington, J, TH.8.6 (159) Renner, M, WP.132 (132) Renz, M, WP.35 (116) Renzullo, P, TP237 (102) Repetti, C, MP.114 (29) Resnick, L, MP.109 (28); MP.146 (34); TP.136 (85); TP.141 (86); WP.1 (110); TH.8.6 (159); THP.155 (I89) Reuben, J, TP.134 (84); TP.218 (98); WP.131 (132); THP.135 (I86); THP.236 (202) Reupke, H, TP.24 (66) Reuter, P, TP.59 (72) Revuz, J, WP.164 (I37) Rey, F, F.2.1 (207) Rey, J, E62 (211) Rey, M, MP.189 (41); T54 (55); TP.27 (67); TP.37 (68); TP.153 (88); WP.87 (124); THP.33 (169); THP.24 (167); THP.169 (I91); F.6.1 (211) Reyes, G, TP.114 (81); TP.115 (81) Rhame, F, TP.231 (101 ); MP250 (51 ) Rhoads, J, TP.166 (90); WP.110 (128); THP.105 (181) Rhodes, R, THP.30 (168) Ricard, D, THP.7 (164); E66 (211) Ricci, L, MP.155 (36); THP.201 (197) Rich, R, THP.114 (182) Richardson, H, MP211 (45) Richardson, S, MP.197 (43) Richman, D, MP.145 (34); MP200 (43); T.8.3 (58); T.8.4 (58); TP.9 (64); TP.61 (72) Richwald, G, WP.189 (141) Rickard, K, M.11.5 (9) Riedel, N, WP.15 (112); TH.2.2 (153); THP.5 (164) Riedener, H, MP.179 (40); MP.180 (40) Rieder, H, THP.86 (177) Riefel, S, F53 (210) Riethmueller, G, T46 (70) Rietmeijer, C, TP.70 ( 74); WP.181 (140) Riggin, C, THP.19 (166) INDEX Rinaldo, C, M.6.2 (4); M2121 (30); T.3.1 (53); T.3.2 (53); T272 (74); T273 (74); W2106 (128); W2117 (129); W2129 (131); 28.3 (213) Rindum, J, M2207 (44); T2161 (89) Rios, A, T2134 (84); T2218 (98); TH2135 (186); TH2236 (202) Ripper, M, TH.11.1 (161) Rivera, J, TH2214 (199) Rivera, Y, W2187 (141) Riviere, Y, M101 (7) Rizza, C, M.11.5 (9); T2250 (104) Rizzardini, G, TH284 (177) Robbins, F, TH2109 (181) Robert-Guroff, M, T.3.3 (53); W32 (106); W233 (115); TH235 (169); 21.2 (206) Roberts, A, TH.8.3 (159) Roberts, J, T2195 (95) Roberts, P, W276 (123); TH273 (175) Roberts, R, M2195 (42); T85 (58) Roberts, W, M.11.6 (9) Robertson, J, M259 (20); T2195 (95 ); W240 (117) Robertson, P, TH2115 (182) Robertson, V, M2156 (36); TH2140 (186) Robey, E, W22 (110) Robey, F, 24.2 (209) Robey, W, M102 (8); M104 (8); M217 (13); M231 (15); T210 (64); W23 (110); W.3.6 (107); 27.6 (212) Robinowitz, M, M.11.6 (9) Robinson, H, TH211 (165) Robinson, W, M25 (11); M26 (11); W297 (126); TH21 (163); T298 (78) Roboz, J, W5.6 (109); W2115 (129) Rodrigues, L, TH2138 (186) Rodriguez, G, M2210 (45); T2206 (96); TH.11.4 (162) Rodriguez, K, W2167 (138) Rodriguez, M, T2147 (87); W2120 (130); TH292 (I78) Rodriguez, S, TH298 (I79); T112234 (202) Rogers, M, T267 (73); T288 (77); T1171 (157); TH.7.2 (157); TH2140 (186); TH2197 (196) Rohrschneider, L, T43 (54) Rokos, H, T225 (66) Rokovich, J, W2246 (151) Rolan, N, M2107 (28) Roland, A, TH257 (173) Roland, J, M2158 (36) Rolsma, G, TH2191 (195) Rolston, K, T2147 (87) Romano, M, TH2118 (183) Romet-Lemonne, J, TH27 (164) Rompalo, A, 21.6 (206) Ronspeck, W, T225 (66) Roodman, S, TH2127 (184) Rook, A, M2103 (27); T296 (78) Roos, M, TH2136 (186) Rosci, M, W2122 (130) Rosello, P, TH2138 (186) Rosen, C, M.4.6 (3); M.9.2 (7); T162 (62); W216 (113) Rosenberg, A, W2100 (127) Rosenberg, B, TH2249 (205) Rosenberg, M, T.6.3 (56) Rosenfeld, L, ”Fl-{285 (177) Rosengren, O, TH296 (179) Rosenheim, M, W279 (123); TH224 (167) Rosenthal, K, T2114 (81) Rossi, G, W2124 (131); TH2248 (204) Rosso, J, W2164 (137) Rotenbourg, J, W287 (124) Roth, D, T282 (76); W259 (120) Rotkiewicz, L, T2206 (96); TH.5.2 (156) Roux, J, T295 (78) Rouzioux, C, M279 (23); TH.7.4 (158); 26.3 (211) Rouzuette, B, W2216 (146) Rowe, M, M2190 (41) Rowland, J, TH218 (166) Roy, A, M254 (19) Roy, M, TH2152 (188) Royce, R, M.3.2(1) Rozakis, M, TH296 (179) Rozenbaum, W, M54 (4); M2112 (28); W2126 (131); TH276 (176); T2229 (100); 22.1 (207) Rubin, D, 23.6 (208) Rubinow, D, TH2146 (187) Rubinstein, A, T2146 (86); W53 (109); W2153 (135); THP.156 (189) Rubinstein, P, T74 (57); TH2156 (189); TH29 (165); TH298 (179) Rubsamen-Waigmann, H, W224 (114) Rucker, R, TH2193 (195) Rudd, R, T2227 (100) Ruddle, N, W2108 (128) Ruff, M, M51 (3) Ruger, R, T235 (68) Rugunda, R, T.1.2 (52) Ruitenberg, E, M274 (22) Ruprecht, R, T262 (72) Rusche, J, T.16.4 (62); W233 (115); TH235 (169) Russo, R, W2126 (131) Rutherford, G, M.3.1 (1); T49 (70); T65 (56); T251 (71); T291 (77); W46 (118); TH2207 (198); 21.4 (206) Rutledge, J, W2174 (139) Ryan, C, M2190 (41) Ryder, L, T2123 (83) Ryder, R, M36 (2); M261 (20); M273 (22); T76 (57); W243 (117); TH.7.6 (158); TH2159 (190); 29.6 (214) Ryser, H, M2179 (40) -S- Saag, M, W.3.3 (107) Saab, A, M292 (25); T.3.1 (53); T32 (53); W264 (121); W2117 (129); W2129 (131) Sabella, W, T2181 (92) Sadaie, M, M96 (7) Safary, A, TH2131 (I85) Saidi, P, TH282 (177) Saimot, A, M2161 (37); T227 (67); T2165 (90); W232 (115 ); W2160 (137); TH2141 (187); TH2161 (190); TH2169 (191); 22.4 (207) Saimot, G, TH2106 (181) St. John, R, M244 (17) St. Lawrence, J, M2174 (39) Salahuddin, Z, M232 (15); M234 (15); M2146 (34); T220 (65); W25 (111); TH23 (I64) Salaun, D, W277 (123) Salaun, J, T165 (62) Salit, I, TH.8.1 (158) 232 Salmon, C, TH2132 (185) Salmon, D, T.5.4 (55) Salmon, P, M.10.1 (7); T2105 (80) Saltzman, B, T267 (73); W25 (106) Saltzman, S, T264 (73); T2174 (91) Samarasinghe, P, W2173 (139) Samet, R, M2197 (43) Sampalis, J, TH2133 (185) Samson, S, W.4.3 (108); W2237 (149); TH253 (172) Samuel, M, TH246 (171); TH247 (171) Sanchez, M, W272 (122) Sandstrom, E, M293 (25 ); W283 (124); TH2130 (185) Sangare, A, E25 (207); 26.2 (211) Sano, K, M28 (11) Santa Maria, I, T2102 (79) Santil, J, T243 (69) Saracco, A, W289 (125); TH284 (177) Sardet, A, M2117 (29) Sargent, P, TH2187 (194) Sarin, P, M21 (10); M224 (14); M2226 (47); T222 (66); T2220 (99); W218 (113); TH2107 (181 ) Samgadharan, M, T219 (65 ); T221 (66); TH297 (179) Sattentau, Q, T24 (63); 11-194 (160); TH.9.6 (160) Sattler, F, M2175 (39); TH.11.1 (161) Sauk, J, W284 (124) Saulsbury, F, M243 (17) Saxinger, C, 24.1 (209) Saxinger, W, 26.4 (211); 26.5 (211) Saykin, A, T52 (55) Scalia, V, T245 (70) Scesney, S, W217] (138); TH22 (163) Schaab, C, T112186 (194) Schaaf, K, W239 (116) Schable, C, M272 (22); M2241 (50); TH.3.5 (155); TH252 (172) Schaeffler, B, W2145 (134) Schafer, A, TH294 (179) Schaffner, C, M2226 (47) Schatz, B, TH2210 (198); 25.5 (210) Schechter, M, M.3.3 (2); M63 (5); M2111 (28); T299 (79) Schechter, P, TH.4.2 (155) Scheffel, C, M2135 (32) Scheffel, J, M2135 (32) Scheibel, E, T2161 (89) Scheiermann, N, TH2131 (185) Schellekens, P, TH2126 (184); TH2136 (186) Schenk, P, T2107 (80) Schenmetzler, C, TH2170 (191) Scheppler, J, W299 (126) Schiattone, M, T2113 (81 ) Schieb, R, T2220 (99) Schietinger, H, TH.3.4 (155) Schiltz, M, M.6.6 (5) Schimpf, K, TH.10.4 (161) Schibdt, M, M2207 (44) Schiodt, M, T2161 (89) Schirm, J, TH.8.2 (158) Schito, G, W2151 (135) Schletty, S, T.7.5 (57); W2235 (149) Schmidt, R, T2200 (95) Schmitz, H, M228 (14) INDEX Schneider, C, WP.48 (118) Schneider, J, MP.28 (14) Schocheiman, G, THP.28 (168); THP.52 (172) Schoenbaum, E, M.3.4 (2); MP.156 (36); WP.41 (117); TH.7.2 (157); THP.41 (170); THP.140 (186) Schonberger, L, ”£52 (55) Schooley, R, T.9.1 (59); WP.104 (127) Schorr, J, THP.77 (176) Schorr, R, MR86 (24) Schoub, B, MP.58 (19) Schppers, W, WP.51 (118) Schrager, L, MP.155 (36); TP.143 (86) Schramm, W, TH.10.4 (161); TH.10.6 (I61) Schreiber, K, TP.143 (86) Schroder, H, MP1 (10) Schulman, D, E5.6 (210) Schulman, S, M.11.5 (9) Schulof, R, MP.24 (14); MP.216 (46); T.8.6 (58); TP.220 (99) Schultz, S, MR83 (24); TP.42 (69); WP.155 (136) Schulze, T, THP.36 (169) Schumacher, R, WP.244 (151) Schuman, R, WP.183 (140) Schupbach, J, THP.14 (165) Schwartlander, B, TP.25 (66) Schwartz, T, MR51 (18) Scott, A, TP.239 (102) Scott, G, MR38 (16); MP.116 (29); WP.105 (127); WP.166 (138); THP.91 (178); THP.167 (191); E22 (207) Scott, H, MP.185 (41) Scrobohaci, M, MR98 (26) Seage, 111, G, MR89 (25); TP.47 (70); WP.210 (145) Scale, J, THP.205 (197) Secord, K, MP.232 (48) Seebacher, C, THP.89 (178) Segal, A, THP.92 (178) Sehgal, P, TP.94 (78); E73 (212) Sei, Y, MP.132 (32); TP.131 (84); WP.114 (129); THP.117 (183) Seibert, G, THP.221 (200) Seidl, O, TP.213 (98) Seidlin, M, THP.214 (199) Seligmann, M, TP.216 (98); WP.228 (148) Selik, R, TP.88 (77); WP.56 (119) Selleri, L, TP.112 (81) Selnes, O, MP.142 (33) Selwyn, P, M.3.4 (2); MP.156 (36); WP.41 (117); TH.7.2 (157); THP.41 (I70); THP.140 (186) Sension, M, THP.19 (166); THP.159 (190) Serrato, C, TP.59 (72) Sethi, N, E32 (208) Sette, P, THP.76 (I76) Sever, J, MP.144 (34); TP.151 (87); THP.108 (181) Shah, K, TP.68 (73); WP.153 (135) Shah, P, THP.158 (189) Shahied, S, MP.226 (47) Shapshak, P, MR8 (11); MP.108 (28); MP.109 (28); THP.160 (190) Sharer, L, THP.21 (167) Sharma, 0, WP.55 (119) Sharma, V, TP.114 (81 ) Sharpe, A, TP.62 (72) Shattls, W, WP.183 (140) Shaukat, M, TP.141 (86) Shaw, G, W.3.3 (107); WP.11 (112); TH.2.3 (153) Shearer, G, TP.116 (81 ); WP.100 (127) Shelov, S, TH.3.3 (154) Shepard, C, MP.75 (22) Shepard, D, THP.138 (186) Shepherd, F, MR49 (18); MRSO (I8); MP.209 (45); TP.224 (99) Shepp, D, T92 (59); WP.85 (124); THP.120 (183) Sher, J, WP.170 (138) Sher, R, M.8.2 (6); MR42 (17) Sherr, L, T62 (56) Shih, J, WP.249 (151) Shiigi, S, WP.34 (116) Shimasaki, C, WP.12 (112) Shine, K, WP.178 (I40) Shinozuka, K, T.4.4 (54) Shiota, J, W.4.3 (108) Shriver, C, MR84 (24) Shriver, K, MP.35 (16); TP.32 (67); WP.65 (121); WP.145 (134) Shu, S, T.4.6 (54) Shuh, M, TP.39 (69) Shulman, J, MP.156 (36) Shultz, J, MP.193 (42) Shuster, J, TP.89 (77); WP.163 (137) Sicard, J, MP.158 (36) Siccardi, A, WP.124 (I31) Sidhu, G, E3.6 (208) Sidorovich, I, MP.97 (26) Sidtis, J, T.5.1 (55); WP.148 (I35); THP.153 (189) Siegal, F, TP.68 (73); TP148 (87); WP.29 (115); WP.109 (128); THP.228 (201); THP.233 (202) Siege], K, T102 (60); TP.171 (91) Siegenthaler, W, WP.81 (123) Siegler, M, TP.212 (97) Siegman-Igra, Y, MRSI (18) Sijin, O, TP.78 (75); WP.75 (122) Sikes, R, W21 (105) Silcott, J, THP.158 (189) Silva, D, MR72 (22) Silverman, H, MP.181 (40) Simberkoff, M, TP.163 (89); E3.6 (208) Simek, L, WP.21 (113) Simmonds, P, MP.245 (5]) Simmons, J, TP.209 (97) Simoen, E, THP.131 (185) Simon, G, MP.216 (46); TP.220 (99) Simonsen, J, M84 (6); MP.91 (25) Simooya, O, MP.77 (23) Simpson, M, MP.193 (42) Sims, J, THP.45 (171); THP.83 (177) Sinclair, A, MP.122 (30) Singer, M, MP.205 (44) Singer, R, THP.2 (163) Singh, B, TH.9.2 (159) Sisson, B, WP.22 (114) Sito, A, MP.107 (28) Sivertson, K, TH.3.6 (155) Siziya, S, MP77 (23) Sjoerdsma, A, TH.4.2 (155) Skidmore, C, MP.59 (20); TP.195 (95); WP.40 (117) Skinner, K, WP.204 (144) Sklizovic, D, THP.110 (181) Skurkovich, S, MP.18 (13) Slaterus, K, MP.220 (46) 233 Slim, J, MP.160 (36); THP.171 (192) Small, C, THP.201 (197) Smiley, L, MR78 (23) Smit Sibinga, C, TP.193 (94); THP.191 (195) Smith, A, MP9 (11); MP.58 (19) Smith, C, M.5.1 (3) Smith, D, M.4.4 (3); TP.31 (67) Smith, G, MP.16 (12); W.3.4 (107) Smith, L, THP.105 (181 ) Smith, P, MP.133 (32); TP.133 (84); WP.130 (132); THP.134 (185) Smith, R, MP.237 (49) Smith, S, MP.196 (42) Smith, T, TP.32 (67) Snape, T, TP.250 (104) Snider, D, THP.86 (177) Sninsky, J, WP.23 (114); F.2.3 (207) Sninski, J, THP.28 (168) Snyder, H, MP.231 (48) Sobel, A, WP.164 (I37); THP.123 (I84) Sobesky, G, MR96 (26) Sodroski, J, M.4.6 (3); M.9.2 (7); T162 (62); T43 (54); WP.16 (113) Soeken, K, TP.172 (91 ) Solinger, A, WP.133 (132) Solomon, G, M.5.5 (4) Solomon, S, WP.55 (119) Somaini, B, MP.S6 (19); MP.179 (40); MP.180 (40) Somasundaran, M, THP.11 (165 ) Sonigo, P, TH.2.1 (153) Sonnerborg, A, TH.1.3 (153) Sonnex, C, WP.173 (139) Sooy, C, TP.130 (84) Soskolne, C, MP.49 (18); MPSO (18) Sotheran, J, THP.67 (174); THP.178 (I93) Soumenkoff, G, WP.80 (123) Sparger, E, E75 (212) Spear, J, TP.225 (100); WP.9 (111) Spech, T, TP.162 (89) Spechko, P, WP.234 (149) Spector, S, MP.145 (34); MP.200 (43); TP.61 (72) Spencer, N, MP.192 (42); TP.185 (93); WP.176 (139); THP.174 (192) Sperling, J, MP.175 (39) Spero, J, TP.236 (101) Spira, T, MP.127 (31); T.5.2 (55); WP.99 (126); THP.42 (170); THP.69 (175); THP.100 (180) Spire, B, MP37 (16); WP.37 (116) Spooner, R, TP.250 (104) Sprecher-Goldberger, S, MP.124 (30); MP.154 (35); WP.80 (123); THP.227 (201) Sprenger, H, TH.8.2 (158) Spross, J, THP.219 (200) Squillace, K, THP.146 (187) Sridhar, P, T95 (59) Srinivasan, A, MP.26 (14); TP.36 (68) Sroka, S, TP.182 (92) Stall, R, THP.80 (176); E82 (213) Staloch, L, TP.208 (97) Stamm, W, F.1.6 (206) Stanback, M, M.8.6 (6); TP.43 (69) Stapleton, D, TP.18 (65); WP.6 (111) Starcher, T, TP.57 ( 72); TP.84 (76); WP.88 (125) Starcher, II, E, WP.190 (142) Starcich, B, WP.20 (113); TH.2.4 (154) Staub, R, MP.179 (40); MP.180 (40) INDEX Stavrou, D, MP.104 (27) Steben, M, WP.179 (140) Steel, C, MP.137 (33); MP.245 (51); TP.124 (83); TP.238 (102); WP.102 (127) Steel, M, MP.S9 (20) Stehr-Green, J, WP.82 (124) Steigbigel, N, W.2.5 (106); TH.3.5 (155) Steigman, C, TP.169 (90) Steimer, K, TP.39 (69); TH.9.2 (159); THP.38 (169) Stein, A, WP.90 (125) Stein, B, MP.12 (12) Stein, J, TP.191 (94); WP.185 (I41); THP.184 (194) Stein-Streilein, J, THP.143 (187) Steinbeck, A, THP.168 (191) Steinhauer, E, THP.156 (I89) Steis, R, THP.226 (201) Stempel, R, WP.199 (143) Stenberg, M, TP.229 (100) Stepanova, L, THP.40 (170) Stephans, J, TP.39 (69); THP.38 (169) Sterk, C, THP.196 (196) Stern, M, THP.239 (203) Stevens, C, T.7.4 (57); TP.12 (64); THP.98 (179) Stevens, R, THP.45 (171); THP.83 (177) Stingl, G, TP.107 (80) Stites, D, M55 (4); MP.120 (30); T.121 (82); T45 (54); TH.9.2 (159); WP.111 (128); E95 (214) Stocking, C, TP.212 (97) Stoddard, A, TP.64 (73); TP.174 (91); WP.172 (139) Stoler, M, TP.149 (87) Stoller, E, T65 (56) Stoller, L, WP.178 (140) Stone, G, THP.108 (181) Stoneburner, R, MR83 (24); TP.42 (69); TP.75 (75); WP.70 (122); WP.71 (122); THP.67 (174) Stool, E, MP.217 (46) Strang, J, THP.137 (186) Strawczynski, H, TP.89 (77); WP.163 (137) Strayer, D, MP.216 (46) Strebel, K, M.9.4 (7) Strehl, L, TP.35 (68); WP.28 (115); THP.27 (168) Strickland, P, MP95 (26); WP.85 (124) Stringari, S, T.5.5 (55) Strobert, E, MP27 (14); F.7.2 (212) Stroud, F, WP.178 (140) Strunin, L, T66 (56) Strykowski, H, MP.102 (27) Stuck, B, THP.94 (179) Stutsman, A, TP.191 (94) Stutz, T, MP.56 (19) Su, P, TP.32 (67) Su, S, WP.146 (134) Sugita, K, MP8 (11); THP.160 (190) Sukrow, S, THP.36 (169) Sullivan, C, TP.231 (101) Sullivan, J, M.11.4 (9); MP.86 (24); MP.240 (50); TRIM (86); WP.171 (I38); THP.2 (163) Sullivan, M, WP.239 (150) Sun, D, MP.24 (14); MP.226 (47) Sun, N, THP.160 (190) Sunderland, A, THP.209 (198) Suni, J, TH.9.3 (160) Sutherland, S, THP.137 (186) Sutjipto, S, MP.230 (48) Sutoh, H, W.3.2 (106) Suurmeyer, T, TP.193 (94); THP.191 (195) Svejgaard, A, WP.101 (127) Svenson, M, MP.113 (29) Swack, N, MP.129 (31 ) Sweet, D, WR201 (143) Swenson, R, F.7.2 (212) Swerdloff, M, MP.139 (33) Swift, R, TH.5.1 (156) Switzer, W, MP.27 (14); MP72 (22); F.7.1 (212) Szapocznik, J, MP.116 (29) _T_ Taelman, H, MP.82 (23); MP.154 (35); TP.82 (76); W.2.4 (106); THP.227 (201) Taggart, V, MP.188 (41) Tagliabue, A, THP118 (183) Takatsuki, K, W.3.2 (106) Takeda, A, WP.30 (115) Takeuchi, Y, WP.31 (115) Tam, M, WP.145 (134) Tambussi, G, WP.89 (125) Tan, P, WP.247 (151) Tan, S, WP.215 (146); THP.96 (179) Tapko, J, T.5.6 (55) Tasker, M, MP.213 (45); WP.213 (145) Taswell, H, MP.147 (34) Tateno, M, WP.7 (111) Tatuta, C, WP.30 (115 ) Tauber, M, WP.81 (123) Taylor, D, TH.4.4 (156) Taylor, E, WP.66 (121 ) Taylor, H, M.6.4 (5) Taylor, J, MP.199 (43) Taylor, M, TH.2.3 (153) Taylor, P, T.7.4 (57); TP.12 (64); THP.98 (179) Taylor-Robinson, D, TH.4.4 (I56) Tedder, R, MP9 (11) Tegtmeier, G, WP.244 (151) Teirlynck, O, THP.227 (201 ) Temoshok, L, M55 (4); WP.201 (143) Tennant, F, TP.54 (71); THP.95 (179) Tenneriello, L, TH.11.5 (162) Tenorio, A, TP.102 (79) Terpstra, F, WP.125 (I31); THP.126 (I84) Terragna, A, TP.83 ( 76); WP.134 (132) Tersmette, M, TP.33 (68); WP.36 (116); WP.73 (122); WP.125 (131); THP.90 (178) Terwilliger, E, M.4.6 (3); M.9.2 (7); T.16.2 (62); WP.16 (113) Teschke, R, T83 (58); TP.158 (88) The, G, TP.52 (71) The, T, TH.8.2 (158) Theodore, T, M.4.5 (3) Thies, H, TP148 (87) Thind, D, TP.103 (79) Thiry, L, MP.124 (30) Thomas, D, TP.248 (103); WP.244 (151) Thomas, F, MP.69 (21) Thomas, J, MP.250 (51); WP.227 (148) Thomas, P, TP.76 (75); WP.155 (136); WP.71 (122); TH.7.1 (157); THP.69 (I75); THP.199 (196) Thompson, D, TP.233 (101 ) Thong, K, TP.90 (77) Thouless, M, MP.15 (12) 234 Tielman, R, M.6.1 (4) Tijmstra, T, TP.193 (94); THP.191 (195) Tillett, G, F.5.4 (210) Tindall, B, MP.63 (20); TP.101 (79); WP.86 (124) Ting, R, WP.21 (113) Tipple, J, TP.208 (97) Tirelli, U, WP.95 (126) Tong-Sarksen, S, M.9.l (6) Tonnessen, G, THP.171 (192) Toossi, Z, MP.105 (27) Tor, J, MP.165 (37); TP.167 (90) Torensma, R, TH.8.2 (158) Torseth, J, THP.125 (184) Tosato, G, THP.10 (165) Tourani, J, THP.239 (203) Tourtellotte, W, MP.108 (28); MP.109 (28) Tracey, E, THP.12 (165) Tramont, E, TP.183 (93); WP.195 (142); THP.173 (I92) Tran, C, MP.128 (31) Traylor, D, MP.135 (32) Tremblay, M, TP.26 (66) Trepo, C, THP.216 (199) Tribe, D, TP.85 (76); THP.26 (167); THP.193 (195) Tross, S, T.10.5 (60) Truman, B, TP.177 (92); W.P.74 (122); WP.61 (120); THP.70 (I75) Tsai, C, THP.30 (168) Tsang, P, MP.132 (32) Tschachler, E, TP.107 (80) Tsoukas, C, TP.89 (77); WP.163 (I37); THP.133 (185) Tuazon, C, TH.4.1 (155) Tucker, J, WP.102 (127) Tung, C, MP.14 (12) Turbitt, P, THP.222 (200) Turshen, J, TP.208 ( 97) Tyms, A, TH.4.4 (156) Tyms, S, TH.8.3 (159) Tyson, R, TP.14 (64) _U_ Ujhelyi, E, MP2] (13); MP.236 (49) Ullrich, P, F.2.3 (207) Ulrich, K, MP.62 (20); TP.81 (76); WP.101 (127); WP.162 (137) Ulrich, P, W.4.5 (I08) Ungerer, L, F.5.3 (210) Usategui, M, MP.238 (49) Ussery, F, MP.217 (46) Uttamchandani, R, TP.168 (90); WP.167 (138) Uyeda, A, TP.6 (63) ' _V.. Vacante, D, MP.159 (36) Vaccher, E, WP.95 (126) Vaglia, A, MP.153 (35) Vaheri, A, TH.9.3 (160) Valdiserri, R, M.6.2 (4); F83 (213); E8.4 (213) Valdivia, L, MP.244 (50); TP.235 (101); WP.44 (117) Valentine, F, THP.9 (165) Valentine, J, WP.187 (I41) Valette, I, MR96 (26) Valinsky, J, WR236 (149) Valle, S, MP.119 (30) Valleron, A, TP.180 (92) INDEX Valway, S, TR58 ( 72); THP.174 (192) Van Dam, J, MR6O (20) Van Den Hoek, J, TP.40 (69); E85 (213) Van de Perre, P, THP.61 (173) Van Der Groen, G, MR82 (23); W.2.4 (106); WP.51 (118); THP.139 (186) Van Der Maaten, M, TH,2.5 (154) Vander Noordaa, J, M.6.1 (4) Van Der Poel, K, WP.73 (122) Van Devanter, N, TP.247 (103) Van Druten, H, MP.74 (22) Van Geel, G, WP.51 (118) Van Griensven, G, M.6.1 (4); MP.177 (39) Van Haastrecht, H, TP.40 (69) Van Horne, J, THP.215 (199) Van Ness, P, W.1.3 (105) Van Raden, M, TH.5.6 (157); E84 (213) Varela-Millot, C, MP.112 (28) Varnier, O, TP.83 (76); WP.151 (135) Vaughan, D, TP.191 (94); WP.185 (141) Vazeux, R, MP2 (10); THP.161 (190) v. d. Bij, W, TH.8.2 (158) v. d. Poel, C, THP.90 (178) Veber, F, TH.7.4 (158) Vedrenne, C, THP.161 (I90) Vellend, H, MR209 (45); H, TH.8.1 (158) Venet, A, THP239 (203) Venkatesan, S, THP.17 (166) Verani, P, THP.248 (204) Vercauteren, G, TP.63 (73); WP.51 (118); TH.7.5 (158) Verdier, R, M.8.6 (6); MP.68 (21); MR69 (21); MP.136 (32) Vergeront, J, MP.182 (40); E52 (210) Vermund, S, TP.66 (73); WP.52 (119) Vernon, A, T.8.6 (58) Vernon, D, THP.167 (191) Veronese, F, TP.20 (65); TP.21 (66) Veronesi, R, MP.48 (18) Verroust, F, MR45 (17) Vestergaard, B, T35 (53) Via, C, WP.100 (127) Viallefont, A, M.5.4 (4) Vianello, L, MR249 (51) Vieira, J, TP.221 (99) Viglianti, G, WP.15 (112); TH.2.2 (153); THP.5 (164) Vigneau, B, WP.179 (140) Vilde, J, WP.138 (133); WP.160 (137) Vinceguerra, V, THP.16 (166) Virmani, R, M.11.6 (9) Vishnubhakat, S, WP.159 (136) Visscher, B, TP.72 (74); WP.63 (120); WP.64 (121); WP.67 (121); THP.60 (173); THP.64 (174); E84 (213) Visser, O, MP.220 (46) Vittecoo, D, MP.149 (35); WP.216 (146) Vittecoq, D, TP.142 (86); F.4.6 (209) v Krogh, G, THP.130 (185) Vogel, R, TP.154 (88) Vogt, M, WP.104 (127) Vogt, R, THP.192 (195) Vogt, W, TP.30 (67) Volberding, P, M.11.2 (9); M.11.3 (9); T81 (58); WP.47 (118); WP.58 (120); WP.150 (135); THP.56 (172); THP.57 (173) Voltolin, L, TP.230 (100) Von Briesen, H, Wp.24 (114) Vonk, M, TP.193 (94) Voordecker, P, MP.154 (35) Vorkauf, H, MP.56 (I9) Voskovitch, J, T71 (57) Vrang, L, THP.13 (165) Vuillecard, E, MP.164 (37) Vujcic, L, THP.120 (183) Vyas, G, W.4.3 (108); W.4.5 (108) Vyas, R, MP60 (20) _w_ Waehter, H, MR99 (26); THP.166 (I91) Wada, S, THP.107 (181 ) Wadsworth, J, THP.202 (197) Wagner, B, MP.199 (43) Wagner, K, TP.135 (85 ) Wahl, L, MP.133 (32),- TP.133 (84); WP.130 (132),- THP.134 (I85) Wahl, S, MP.133 (32); THP.134 (I85) Wahren, B, TP.132 (84) Wain-Hobson, S, ”1116.3 (62); WP.32 (115); WP.127 (131); E24 (207) Wainberg, M, TP.26 (66); WP.8 (111) Wakefield, D, THP.115 (182) Waldenlind, L, THP.130 (185) Waldman, A, TP.240 (102); WP.236 (149) Walker, B, T.4.3 (54); T.9.1 (59); THP.6 (164) Walker, C, MP.163 (37); WP.13 (112); E95 (214) Walker, J, TP.75 (75); TP.91 (77); WP.71 (122); THP.199 (196) Walker, R, T.8.2 (58) Wallace, B, MP.126 (31) Wallace, J, WP.55 (119); WP.115 (129); THP.55 (172) Wallemark, C, T.3.6 (53) Walmsley, S, TH.8.1 (158) Walsh, M, TP.14 (64) Walters, D, MP243 (50) Walters, W, THP.111 (I82) Walton, R, MP.172 (38) Walzer, 1-", MP.219 (46) Wan, W, TP.160 (89) Wang, C, MR243 (50); TP.68 (73); THP.111 (182) Wang, J, MP243 (50); THP.111 (182) Wang, L, MR95 (26) Wang, S, WP.18 (113) Wang, Y, MP.120 (30) Wara, D, MP.163 (37) Ward, H, THP.202 (197) Ward, J, M.3.S (2); MP.169 (38); MR241 (50); W.4.1 (107); WP.190 (142); WP.237 (149); THP.30 (I68); THP.53 (172) Ware, G, TP.185 (93) Warfield, D, THP.42 (170) Warren, R, THP.31 (168) Waselefsky, D, MR36 (16) Wassef, M, MP54 (19) Waters, M, THP31 (168) Watkins, S, MP85 (24) Watson, A, MP.35 (16) Watson, E, WP.19 (113); THP.113 (182) Watson Martin, P, THP.128 (184) Watson-Williams, E, TP.28 (67) Watters, J, T.10.4 (60) Waxdal, M, WP.117 (129) 235 Weatherly, B, WP.100 (127) Weaver, M, M.3.3 (2); M.6.3 (5); TP.99 (79) Webb, G, THP.137 (186) Webber, J, WP.242 (I50) Weber, J, M.10.5 (8); T.3.4 (53); TP.78 (75); TRIM (81); WP.2 (110); WP.75 (122); TH.9.4 (160) Weck, K, MP.19 (13); MP22 (I3) Wei, C, M.4.6 (3) Weidlein, D, MP.152 (35 ) Weigel, I, TH.10.6 (161) Wein, A, TH.11.2 (161) Weinhold, K, M.10.3 (8); MP78 (23); T.9.4 (59); TP.128 (83); THP.235 (202) Weintrub, P, MP.163 (37) Weiser, B, THP.228 (201 ); THP.233 (202) Weisman, H, MP.150 (35 ) Weiss, H, THP.156 (189) Weiss, L, WP.72 (122); WP.154 (I36) Weiss, R, M.10.5 (8); MPZO (13); T.3.4 (53); TP.4 (63); WP.2 (110); TH.9.4 (160); THP.20 (I66) Weiss, S, E65 (211); TP.87 (77) Weits, J, TH.8.2 (158) Welck, U, THP.59 (173) Wells, M, WP.85 (124) Werdegar, D, T49 (70); TP.51 (71); W46 (118) Werner, E, MR99 (26) Wernz, J, WP230 (148) Westphal, H, F.7.4 (212) Wetterberg, L, M52 (3); TH.1.3 (153) Whal, S, WP.130 (132) Whalen, M, WP.13 (112) Whaun, J, TP.237 (102) Whitaker, G, TP.57 (72) White, C, T.7.3 (57); TP.84 (76) White, G, MR78 (23); F.1.3 (206) Whyte, B, MR64 (20); MP.186 (41) Widmark, T, F86 (213) Wiebel, W, THP.80 (176) Wigdahl, B, TP.22 (66) Wigzell, H, MR30 (15); MR39 (16) Wiley, A, THP.183 (194) Wiley, C, TP.158 (88) Wiley, J, TP.91 (77); THP.48 (171); F.1.4 (206); E82 (213) Wilfert, C, THP.235 (202) Wilhelm, S, TP.248 (103) Wilkinson, D, WP.152 (135) Willey, R, M.4.5 (3) Williams, A, TP.59 (72); WP.239 (150); THP.44 (170); THP.242 (203); THP.246 (204) Williams, B, WP.121 (130) Williams, K, MP.181 (40); THP.246 (204) Willingmann, P, WP.26 (114) Willitts, D, MP.S6 (24) Willoughby, A, WP.157 (136); TH.7.3 (I58); THP.158 (189) Willoughby, B, M33 (2); M.6.3 (5); MP.111 (28); TP.99 (79) Wilson, B, WP.34 (116) Wilson, V, TP.96 (78) Winbome, R, WP.185 (141) Winchurch, R, WP.123 (130) Winkel, I, WP.36 (116) Winkelstein, A, MP.121 (30) Winkelstein, W, M32 (1); THP.46 (171); THP.47 (171); THP.48 (171); F.1.4 (206) INDEX Winkler, J, WP.143 (134); WP.144 (134); THP.142 (187) Winn, R, T.7.2 (57); WP.156 (136) Winslow, D, TP.85 (76) Winter, K, TH.7.1 (157) Wintfeld, N, MR205 (44) Wisniewolski, R, THP.111 (182) Witebsky, F, WP.152 (135) Withum, D, THP.45 (171) Witte, J, W.2.1 (105); W.2.3 (106); THP.45 (171); THP.83 (177); THP.86 (177) Wittek, A,;MP.125 (31); THP.71 (175); THP.122 (183) Wiznia, A, TP.146 (86); WP.153 (135); THP.156 (189) Wodak, A, MP.186 (41) Woelfel, M, WP.61 (120); THP.70 (175) Woerle, R, WP.216 (146) Wofsy, C, MR221 (47); TP.219 (99); W.5.5 (109); WP.57 (119); THP.154 (189); E31 (208); E33 (208) Wolf, F, TP.239 (102); TP.58 (72); WP.176 (I39); THP.174 (192) Wolf, S, F.5.1 (210) Wolfe, P, THP.232 (202) Wolff, A, TP.29 (67) Wolff, M, T.5.4 (55) Wolska, J, THP.133 (185) Wong, G, T45 (54) Wong-Staal, F, M.9.5 (7); M.9.6 (7); MR23 (I4); MR25 (14); MP.33 (15); T16] (61); TP.11 (64); TP.125 (83); W.3.3 (107); W35 (107); WP.20 (113); TH.2.3 (153); TH.2.4 (154); TH.9.1 (159); THP.15 (166); THP.23 (167) Wood, C, WP.225 (147) Wood, R, F.1.6 (206) Wood, T, THP.34 (169) Woodard, D, TP.103 (79) Woodard, L, THP.51 (172) Woods, W, WP.186 (141) Woolridge, T, THRZOO (196) Wormser, G, TP.154 (88); TP.211 (97); WP.74 (122) Worobec, S, TP.235 (101) Worrell, C, TH.4.5 (156) Worthington, G, MP.173 (39); TP.204 (96) Woweries, J, THP.94 (179) Wright, C, THP.105 (181) Wright, D, TP.166 (90); WP.110 (128); THP.99 (180) Wright, H, TP.214 (98) Wu, W, T36 (53) Wunderlich, C, MR234 (49) Wunderlich, G, THP.183 (194) Wykoff, R, MP.43 (17) ._Y_ Yala, F, WP.79 (123) Yamaguchi, E, WP.167 (138) Yamamoto, J, F.7.5 (212) Yamamoto, N, M.4.2 (2); M2235 (49) Yanagihara, R, TP.29 (67) Yap, P, MP.137 (33) Yarchoan, R, WP.223 (147); THP.10 (165 ) Yee, J, MP.151 (35); TP.6 (63); TP.28 (67) Yeh, C, MP.152 (35) Yemane-Berhan, T, MR214 (45) Yeoh, E, TP.90 (77) Yetter, R, THP.12 (165) Ying, W, TP.240 (102); THP.243 (204) Yocum, D, MR225 (47) Yoffe, B, WP.113 (129); THP.114 (182) Yokoyama, M, TP.131 (84); WP.114 (129); THP.117 (183) Yoshihara, P, THP.128 (184) Young, L, THP.232 (202) Young, S, MP.208 (44); TP.206 (96) Youmo, J, MP.23 (14) _z_ Zabay, J, WP.96 (126); WP.120 (130) Zacarias, F, THP.138 (186) Zacarias, R, M244 (17) Zacchello, F, MP.153 (35 ) Zachar, V, WP.37 (116) Zadelhoff, A, TP.40 (69) 236 Zagury, D, MP.23 (I4); T16.5 (62) Zagury, J, TH.2.4 (154) Zaizov, R, TH.10.5 (161) Zajac, R, T7.2 (57) Zajdowicz, T, MR71 (22) Zajowicz, T, TP.135 (85) Zanella, A, MR249 (51) Zaner, R, THP.194 (195) Zang, E, T7.4 (57) Zapka, J, TP.174 (91); WP.172 (139) Zarling, J, T95 (59) Zazula, T, WP.148 (135) Zegans, L, TP.203 (96); THP.218 (199) Zeichhardt, H, WP.26 (114) Zeleniuch-Jacquotte, A, THP.69 (175) Zeli, P, THP.84 (177) Zelnick, R, TP.87 ( 77) Zerboni, R, TP.164 (89); WP.161 (137) Zhdanov, V, MR7 (11); WP.98 (126); THP.40 (170) Zhou, E, TH.9.5 (I60) Zich, J, M55 (4); WP.201 (143) Ziegler, J, WP.58 (120); WP.111 (128); THP.57 (173); THP.218 (I99) Ziegler, S, MR241 (50) Ziegler-Heitbrock, L, T46 (70) Zimmerman, D, TP.248 (103); F65 (211) Zissis, G, TP.82 (76); WP.59 (120); W280 (123) Zito, J, WP.109 (128) Zolla-Pazner, S, TP.110 (80); THP.69 (175) Zon, G, T.4.4 (54) Zon, L, TP.122 (82) Zones, J, THP.207 (198) Zook, B, WP.18 (113) Zorr, B, TP.34 (68); WP.26 (114),"1‘1-11225 (167); THP.94 (179) Zoubi, D, MP.161 (37); THP.141 (187) Zoulek, G, THP.93 (179) Zuck, T, THP.52 (172) Zuckerman, A, TP.4 (63) Zuckerman, C, TP.199 (95) Zuger, A, THP.206 (197) U.C. BERKELEY LIBRARIES )Iflllllllllll CDDH‘HELLH