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), which are scheduled for presentation at the IX Conference on AIDS in Berlin, Germany. All information from these summaries is embargoed until presentation time. To pursue these or related stories, call the NIAID Office of Communications at 301-402-1663.
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.
Note: A summary of a recent NIAID meeting about long-term survivors and variations in response to HIV exposure and infection is included in NIAID's press kit for the IX International Conference on AIDS and is available from the NIAID Office of Communications.
"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.