NATIONAL INSTITUTES OF HEALTH National Institute of Allergy and Infectious Diseases Bethesda, Maryland USA HIV INFECTION AMONG GAY AND BISEXUAL MEN IXTH International Conference on AIDS Highlights The following are several summaries from two studies supported by National Institute of Allergy and Infectious Diseases (NIAID), the Multicenter AIDS Cohort Study (MACS) and the San Francisco Men's Health Study (SFMHS). Begun in 1984, MACS follows more than 5,000 gay and bisexual men at risk for or infected by HIV. MACS sites include The Johns Hopkins Medical Institutions in Baltimore, Md., Northwestern University in Chicago, Ill., University of Pittsburgh, Pa., and University of California at Los Angeles. The data analysis center is at Johns Hopkins. The SFMHS, located at the University of California, Berkeley, enrolled 1,034 single men, many of them homosexual or bisexual, in 1984 and 1985. The men were contacted using statistical sampling from 19 census tracts in San Francisco where the AIDS epidemic was most severe. NIAID, a component of the National Institutes of Health (NIH), supports research on AIDS, tuberculosis, allergies, immunology and infectious diseases. NIH is an agency of the U.S. Public Health Service, part of the U.S. Department of Health and Human Services. AIDS-FREE HIV-INFECTED MEN HAVE SLOWLY PROGRESSING DISEASE Oral, Wednesday, June 9, 5 p.m. (11 a.m. EDT) HIV-infected individuals who do not progress to AIDS for more than six years may undergo changes to their immune system and then stabilize to a very slowly progressing disease state, according to NIAID-supported researchers. An analysis of 290 SFMHS participants, revealed that 10 percent had no net loss of the immune system cells, CD4+ T cells, targeted by HIV. However, these men had an average CD4+ T cell count of 400 cells per cubic millimeter (mm3) of blood lower and an average of 250 CD8+ T cells/mm3 higher than uninfected SFMHS men. Changes in other laboratory markers that predict CD4+ T cell loss leads the SFMHS investigators to conclude that HIV disease is slowly advancing even among these men with apparently stable CD4+ T cell counts. The findings also suggest that the broad range in HIV progression rates may be the result of several independent factors interacting in a variety of combinations. "Characterization of HIV-1 Infected Individuals With Long-Term Infection and Stable CD4+ T Cell Levels." Haynes Sheppard, Ph.D., William Lang, M.D., Michael Ascher, M.D., Eric Vittinghoff, Ph.D., Warren Winkelstein, M.D., of the Viral and Rickettsial Disease Laboratory of the California Department of Health, California Pacific Medical Center and the Department of Biomedical and Environmental Health Sciences, University of California at Berkeley. HIV-INFECTED MEN WITH STABLE CD4+ T CELL COUNTS FOR SEVEN TO EIGHT YEARS Poster, Tuesday, June 8, 11:30 a.m. (5:30 a.m. EDT) A MACS study has identified a group of men who have not lost the critical immune system cells that HIV targets, called CD4+ T cells, despite seven to eight years or more of HIV-infection. Laboratory investigations already under way could reveal information about specific immune responses in these men and the characteristics of the virus that infects them that accounts for their stable states of infection. When MACS began in 1984, 1,809 of the men enrolled had HIV infections. For this investigation, scientists selected 293 who had not received any zidovudine (AZT) and whose CD4+ T cells had been measured at intervals for at least seven years. For this study, the researchers are comparing immune response and viral characteristics between men whose CD4+ T cells had not declined for at least seven years and those who had intermediate rates of decline and those showing the most rapid rates of decline. The men did not differ by risk factors for acquiring HIV, by history of sexually transmitted disease, by estimated duration of infection prior to enrolling in MACS nor by levels of certain immune system proteins or other factors. Of the group with stable counts, none has developed AIDS. Of those with intermediate rates of decline, 7 percent have developed AIDS, while 79 percent of the most rapid progressors have developed AIDS. Of the rapid progressors, 64 percent have died. Further laboratory investigations may explain the different rates of CD4+ T cell destruction that is apparent among these three groups. "HIV-1 Infected Men With Stable CD4 Numbers." John P. Phair, M.D., Alvaro Munoz, Ph.D., Richard Kaslow, M.D., M.P.H., Barbara Visscher, M.D., Charles Rinaldo, Jr., Ph.D., and Joseph Margolick, M.D., of Northwestern University, Chicago, Ill.; The Johns Hopkins Medical Institutions, Baltimore, Md.; NIAID; University of Pittsburgh, Pa.; and University of California at Los Angeles. RAPID PROGRESSION TO AIDS AMONG HIV-INFECTED MEN Poster, Tuesday, June 8, 11:30 a.m. (5:30 a.m. EDT) Men who rapidly progress to AIDS after becoming infected with HIV have greater changes in their blood and immune systems than those who develop AIDS over a longer period, according to NIAID-supported researchers. These MACS findings suggest that the men have different responses to the virus than those of men with slower progression of disease, which if understood in detail could lead to improved therapy for AIDS. For the investigation, scientists compared 448 MACS participants who became infected with HIV since 1984. The researchers grouped the men according to disease progression: 20 developed AIDS in less than three years; 24, in three to five years; 30, in more than five years; and 81 who have not developed AIDS in at least six years. The men who developed AIDS in less than three years had the greatest decline in percent of lymphocytes and in CD4+ T cells. HIV targets and kills CD4+ T cells. These men and those who developed AIDS in three to five years had similar declines in platelets. AIDS-free men had the smallest declines in two proteins produced by immune system cells, neopterin and microglobins. "Characteristics of Seroconverters Who Rapidly Progress to AIDS." Alfred Saah, M.D., M.P.H., N. Galai, John P. Phair, M.D., L. Park, Charles R. Rinaldo, Jr. Ph.D., Roger Detels, and the MACS, Johns Hopkins University, Baltimore, Md. MARKERS OF AIDS-FREE TIME Poster, Tuesday, June 8, 11:13 a.m. (5:30 a.m. EDT) Measurements of certain factors in the blood of HIV-infected men can help scientists determine the amount of AIDS-free time a person might have, according to NIAID-supported scientists. In the MACS investigation, researchers examined four groups of HIV-infected men: those who became HIV-infected during MACS and developed AIDS in less than three years, those who became HIV-infected but did not develop AIDS after six years or more, those who entered the study with HIV infection but did not have any declines in the immune system cell, CD4+ T cell, which HIV targets and kills, and those already infected who have had a moderate drop in CD4+ T cells during the six years of follow-up. The scientists found the HIV protein, p24, in only 17 percent of the men who did not develop AIDS compared to 55 percent of those who developed AIDS rapidly. Similarly, 10 percent of the men with stable CD4+ T cells had measurable p24 compared to 40 percent of those with moderate declines. Furthermore, AIDS-free men had higher levels of antibodies against p24. Measures of viral RNA confirmed the findings. "Serologic Predictors of AIDS-Free Time and Markers of Progression to Disease: A MACS Report." Homayoon Farzadegan, Dennis Henrard, Cindy Black, Anne Voltz, Alfred Saah, John P. Phair, et al., Multicenter AIDS Cohort Study, Baltimore, Md., and Abbott Laboratories, Chicago, Ill. ***************************************************************** NEWS FROM NIAID National Institute of Allergy and Infectious Diseases YOUNG GAY MEN NOT HEEDING AIDS MESSAGE, RATES OF INFECTION REMAINS HIGH The failure of gay men younger than 30 to protect themselves against HIV--particularly during anal intercourse--has led to a 17.4 percent rate of HIV infection, which is substantially lower than rates first seen in young gay men in the early 1980s but unacceptably high, according to findings of a study supported by the National Institute of Allergy and Infectious Diseases (NIAID). In 1992, investigators for the study, the San Francisco Young Men's Health Study (SFYMHS), screened for HIV infection among 425 gay and bisexual men aged 18 to 29 randomly selected using sampling methods from 21 census tracts of the city. Overall, 74 men or 17.4 percent had HIV. By age group, the infection rates climbed from 4.5 percent among men aged 18 to 23 to 10.7 percent among the 23 to 26 year-olds and to 28.4 percent among those aged 27 to 29, reports Dennis Osmond, Ph.D., investigator in SFMHS at the University of California at Berkeley and San Francisco. Dr Osmond plans to discuss the data during an oral presentation June 8, at the IX International Conference on AIDS in Berlin. "Most of the men aged 26 or younger have been sexually active since 1985 or later--after awareness of AIDS had become widespread in the homosexual community of San Francisco," explains Dr. Osmond. "Although these young gay men have grown up during a decade of increased public awareness of how the AIDS virus is transmitted, they have not fully adopted behaviors that would lower their risk for infection." For example, Dr. Osmond reports that the number of sexual partners the SFYMHS participants had during the previous 12 months related to their risk of infection: a 2.4 percent rate among those without partners, 12.1 to 17.3 percent among those with one to nine partners and 30.8 percent of those with 10 or more partners. Specifically, the association between HIV infection and the number of partners during the past year was even stronger among men who acted as the receptive partner during anal intercourse (RAIs), a behavior that puts one at very high risk for becoming infected with HIV, explains Warren Winkelstein, Jr., M.D., M.P.H., principal investigator of SFYMHS, and professor of epidemiology at the University of California at Berkeley. While the 151 men who were not RAIs had an HIV infection rate of 8.6 percent, RAIs who had one partner had a rate of 16.7, those with two to four partners, 14 percent, five to nine partners, 34.5 percent and those with 10 or more partners, 55.9 percent. "These alarmingly rates of high risk activities show that these men, unlike older gay men, have failed to take preventive messages to heart," says Lewis K. Schrager, M.D., SFYMHS project officer and chief of the epidemiology section of the Vaccine and Trials and Epidemiology Branch in NIAID's Division of AIDS. By analyzing the study data, the SFYMHS investigators estimate that an annual rate of new HIV infections at 2.9 percent overall among gay men aged 18 to 29 in the city. While men, aged 27 to 29 had the highest estimated annual rates of new infections, 3.6 percent, the researchers calculated lower rates for younger men: a 1.5 percent rate among those aged 18 to 23 and a 1.9 percent rate for those aged 24 to 26. Other studies have estimated infection rates of 0.8 to 0.9 percent among gay men older than 30 in the San Francisco area, Dr. Osmond reports. These findings suggest, Dr. Winkelstein explains, that as the young men begin sexual activity, they do not strongly identify with the epidemic nor do they personalize the sense of risk of their activities. "Because of their youth and the long period of disease-free state before full-blown AIDS occurs, these younger people have not yet gone through the loss to AIDS of friends and loved ones that older gay men have experienced," says Dr. Winkelstein. NIAID, a component of the National Institutes of Health (NIH), supports investigators and scientific studies at universities, medical schools, hospitals and research institutions in the United States and abroad aimed at preventing, diagnosing and treating such illnesses as AIDS, tuberculosis, allergies and asthma. NIH is an agency of the U.S. Department of Health and Human Services. Drs. Osmond, Winkelstein and Shrager's coinvestigators include James A. Wiley, Ph.D., Thomas Coates, M.D., Haynes W. Sheppard, Ph.D., Kim Page, M.P.G., Michael Ascher, M.D., Andrew Moss, Ph.D., Karen Garrett, Thomas Piazza, Ph.D., Edwin Charelbois, M.P.H., Michael Samuel, Dr.P.H., William Lang, M.D., and Robert Hays at the University of California, Berkeley and San Francisco and at NIAID. * * * * * * * * * * * * * * * * * * * * * * * U.S. Department of Veterans Affairs * * AIDS Information Center * * Michael Howe, MSLS * * * * Library Service (142D) Voice: 415-221-4810 * * VAMC San Francisco ext 3305 * * 4150 Clement Street FTS: 700-470-3305 * * San Francisco, CA 94121 FAX: 415-750-6919 * * * * Internet address: hivinfo@itsa.ucsf.edu * * * * * * * * * * * * * * * * * * * * * *