NATURAL HISTORY OF HIV-1 INFECTION IN HOMOSEXUAL AND BISEXUAL MEN

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The Study to Help the AIDS Research Effort (SHARE) is one of the four clinical sites of the Multi center AIDS Cohort Studies (MACS). MACS consists of four clinical sites and a data coordinating center (CAMACS). The other three clinical sites are Northwestern University, Chicago Illinois, UCLA School of Public Health, Los Angeles California, and University of Pittsburgh - Graduate School of Public Health Pittsburgh, Pennsylvania. The study was originally funded in 1984 to study the natural history of HIV infection in homosexual and bisexual men. The GCRC is utilized as the primary site for participant visits, the source of data collection: blood and other biological specimens, physical, health survey and questionnaire. Clinic is held two evenings a week, with special arrangements made for participants who are unable to make regular clinic hours. Long-term substudies (Neuropsychological) and new studies (Gallo Chemokine and Health Policy Research) are coordinated in and out of the primary study on a regular basis. Current research focuses on many aspects of HIV infection and disease progression. Neurological studies, which started in 1987 continued to screen all consenting SHARE participants and during 1997 tested over one hundred eighty HIV seropositive participants. Clinical outcomes, particularly HIV-associated dementia and HIV-associated sensory neuropathy, are identified, reviewed and reported to the central data center (CAMACS). We have been able to document a decline of the annual incidence rates of HIV-associated dementia (compared to the CDC national surveillance figures). This probably reflects the impact of highly active antiretroviral therapy which is now widely used in the cohort. The malignancy and autopsy programs remain an integral part of the local study. We have experienced a marked decline in the number of deaths within the cohort and during the period of this report, we had three participants die from HIV related illnesses. The process of enrolling participants in these programs is an ongoing process. Immunological studies continue to focus on T cell homeostasis which postulates the existence of a physiologic mechanism that maintains constant numbers of T lymphocytes in the peripheral. We previously documented in a MACS-wide study (Margolick et a], Nature Medicine 1:674-680, 1995) that constant T cell numbers per ul of blood were maintained for up to 8 years after seroconversion, except in people who developed clinically-defined AIDS. In the later population, the homeostatic mechanism failed preceding AIDS, with an average lag of approximately 2 years prior to AIDS (clinical definition). The cohort continues to serve as a resource to investigators who have an interest in studying the various stages of HIV infection. Among the studies conducted this year was an investigation with Dr. Robert Gallo's group at the Institute of Human Virology, University of Maryland. We are studying whether chemokine levels in vivo and in vitro have an impact on disease progression. Dr. Gerald Quinnan, Uniformed Services University of the Health Sciences. This study involves preparation of HIV virions and pseudovirions from MACS participants, and testing the development of neutralizing antibody titers in these individuals. One advantage of the methods being developed is that these titers can be measured in systems that are not infectious for HIV.