This application is to renew the Multicenter AIDS Cohort Study (MACS), a comprehensive quality-assured prospective cohort study of over 7000 men, which has contributed almost 1300 research papers on the natural history of HIV infection and the impact of effective combination antiretroviral therapies (cART). The follow-up of the existing cohort with continuing dynamic enrollment will enable elucidation of long-term effects of cART, including newer and evolving cART regimens, in men who have sex with men (MSM), the largest population impacted by HIV in the U.S. The overarching goals of the MACS are to continue to elucidate the biology of infection and the clinical outcomes of treated and untreated infection, combining immunologic, virologic, genetic and psychosocial approaches. The scientific agenda of the MACS focuses on four primary areas: 1) clinical epidemiology of HIV-related and non-AIDS-defining outcomes with particular emphasis on the effects of cART and age;2) pathogenic mechanisms underlying HIV susceptibility, disease progression and treatment response including genetic and other molecular factors;3) psychosocial factors, including substance use which influence risk of HIV infection, co-morbidities and treatment utilization;and 4) development of novel applied methodology. Following HIV-uninfected MSM with the same standardized protocols will facilitate distinguishing the contributions of HIV, age, genetics,co-infections and behaviors on the development of non-AIDS-defining outcomes including malignancies, and aging. The role of unresolved inflammation and immune activation, and more rapid senescence of the immune system, on disease course in treated HIV will be investigated. Data with linked specimens, particularly from over 700 HIV seroconverters, provides an unparalleled resource for studying the entire natural history of HIV, ranging from pre-infection (e.g. susceptibility) to infection, through treatment to old age and death. The MACS is and will continue to be ideally positioned to address these issues because of its long-term standardized follow-up, an extensive repository of over 1 million specimens that have been collected semiannually since 1984, an appropriate control group of HIV- MSM, and a seasoned and expanding cadre of experienced investigators.

Public Health Relevance

In the US, the highest HIV incidence is among men who have sex with men (MSM), and with effective treatment, the median age of HIV-infected persons is soon expected to be 50 years. The MACS is ideal for elucidating biological and psychosocial effects of aging with HIV, and effects of evolving therapies on biomarkers related to resulting outcomes. The proposed research will provide information for development of vaccines for HIV as well as for the prevention of AIDS-defining and non-AIDS defining outcomes.

National Institute of Health (NIH)
National Institute of Allergy and Infectious Diseases (NIAID)
Research Project with Complex Structure Cooperative Agreement (UM1)
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Special Emphasis Panel (ZAI1-NLE-A (J1))
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Roe, Joanad'Arc C
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Johns Hopkins University
Public Health & Prev Medicine
Schools of Public Health
United States
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Hart, Trevor A; Mustanski, Brian; Ryan, Daniel T et al. (2015) Depression and sexual dysfunction among HIV-positive and HIV-negative men who have sex with men: mediation by use of antidepressants and recreational stimulants. Arch Sex Behav 44:399-409
Becker, James T; Kingsley, Lawrence A; Molsberry, Samantha et al. (2015) Cohort Profile: Recruitment cohorts in the neuropsychological substudy of the Multicenter AIDS Cohort Study. Int J Epidemiol 44:1506-16
Seaberg, Eric C; Thio, Chloe L (2014) A closer look at hepatitis C clearance in HIV controllers. AIDS 28:1242-3
Pines, Heather A; Gorbach, Pamina M; Weiss, Robert E et al. (2014) Sexual risk trajectories among MSM in the United States: implications for pre-exposure prophylaxis delivery. J Acquir Immune Defic Syndr 65:579-86
Althoff, Keri N; Jacobson, Lisa P; Cranston, Ross D et al. (2014) Age, comorbidities, and AIDS predict a frailty phenotype in men who have sex with men. J Gerontol A Biol Sci Med Sci 69:189-98
Wada, Nikolas; Jacobson, Lisa P; Cohen, Mardge et al. (2014) Cause-specific mortality among HIV-infected individuals, by CD4(+) cell count at HAART initiation, compared with HIV-uninfected individuals. AIDS 28:257-65
Rizvi, Syed Monem; Salam, Nasir; Geng, Jie et al. (2014) Distinct assembly profiles of HLA-B molecules. J Immunol 192:4967-76
Nolen, Brian M; Breen, Elizabeth Crabb; Bream, Jay H et al. (2014) Circulating mediators of inflammation and immune activation in AIDS-related non-hodgkin lymphoma. PLoS One 9:e99144
Margolick, Joseph B; Jacobson, Lisa P; Schwartz, George J et al. (2014) Factors affecting glomerular filtration rate, as measured by iohexol disappearance, in men with or at risk for HIV infection. PLoS One 9:e86311
Pickering, Suzanne; Hué, Stephane; Kim, Eun-Young et al. (2014) Preservation of tetherin and CD4 counter-activities in circulating Vpu alleles despite extensive sequence variation within HIV-1 infected individuals. PLoS Pathog 10:e1003895

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