The Multicenter AIDS Cohort Study (MACS) was a longitudinal study of HIV-1 infection among gay and bisexual men in the United States. The MACS began in 1984 and has enrolled more than 7,300 study participants who were evaluated every six months. The visit protocols included in-depth interviews, physical examinations and the collection of biological specimens for testing and repository storage. Information about HIV seroconversions, AIDS diagnoses and/or deaths is reported on a continuous basis.
The overall objectives at the time of the initial funding were to:
- Observe and study the early causal and clinicopathologic events (natural history) of the disease in enough initially uninfected persons to yield a number of cases of AIDS sufficient for meaningful estimates of risk.
- Elucidate the relationships between AIDS and risk factors suspected of initiating or modulating the disease process.
- Establish a repository of biologic specimens as a resource for any investigator to pursue promising ideas about the origins and course of immunodeficiency.
- Study psychological and behavioral characteristics and their interactions.
- Examine the manifestations and determinants of the infectious process in different times and places.
As a consortium of four clinical research sites and a data coordinating center, the MACS recruited and retained participants, collected and stored clinical specimens, and conceptualized, designed, and implemented a multidisciplinary, interdependent scientific agenda and research plan. Our ability to respond rapidly to a changing epidemic, whether it be the advent of effective combination antiretroviral therapy (cART) or a shifting demographic, allowed the MACS to address the key questions facing HIV research today, including the effects of HIV, cART, and age on HIV-induced inflammation and immune dysfunction and on non-AIDS-defining outcomes including cancer, cardiovascular, liver, metabolic, neurologic, psychologic, and renal disease.
The Women’s Interagency HIV Study (WIHS) was a multicenter longitudinal study to investigate the progression of HIV disease in women. The WIHS started in 1993 in response to growing concern for the impact of HIV in women. WIHS has enrolled nearly 5,000 women and their data, along with other cohort studies, provide a basis for describing the full spectrum of the natural and “treated” history of HIV infection. For more than 20 years, the WIHS investigated topics such as women’s reproductive health, clinical outcomes (for example, cardiovascular disease, diabetes, and others), and the effectiveness of antiretroviral therapy.
In addition to the cohort’s strong focus on issues relevant to women who reflect the epidemiology of HIV in the U.S., the study design had several notable strengths:
- WIHS implemented protocols that prospectively collected both the most important markers of HIV disease progression (e.g., T-cell subsets and HIV RNA levels), as well as novel measures not routinely collected in clinical care settings (such as body habitus measures, tissue, PK samples, metabolic panels, frozen cells), and linked these data to the extensive data collected as part of the core protocol.
- The WIHS cohort was representative of AIDS and HIV cases reported among women in the U.S.
- WIHS implemented a standard schedule of visits that was independent of clinical care and maintained high retention of a historically-neglected study population that continues to be under-represented in clinical research in the U.S.
- WIHS data and specimen collection methods were protocol-driven and conducted by dedicated study personnel. This allowed the study to implement quality assurance methods and standardization of data collection.
- WIHS recruited a demographically-similar group of HIV-negative women and collected information and specimens from these women in a fashion identical to that of women living with HIV.
- WIHS implemented nested sub studies that capitalized on the extensive core, longitudinal database and specimen repositories.
- WIHS maintained sufficient numbers of women to answer research questions that are unique to women, and partnered with similar studies that are exclusively (e.g., MACS) and/or primarily (e.g., ALIVE) male to perform investigations comparing men and women.
- WIHS provided extensive opportunities for collaboration to new investigators. The WIHS had an established, open set of guidelines for providing access to specimens, data, and participants.