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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Mukerji, Shibani; Haghighat, Roxanna; Misra, Vikas et al. (2017) Longitudinal Modeling of Depressive Trajectories Among HIV-Infected Men Using Cocaine. AIDS Behav 21:1985-1995
McKay, Heather S; Margolick, Joseph B; Martínez-Maza, Otoniel et al. (2017) Multiplex assay reliability and long-term intra-individual variation of serologic inflammatory biomarkers. Cytokine 90:185-192
Dubrow, Robert; Qin, Li; Lin, Haiqun et al. (2017) Association of CD4+ T-cell Count, HIV-1 RNA Viral Load, and Antiretroviral Therapy With Kaposi Sarcoma Risk Among HIV-infected Persons in the United States and Canada. J Acquir Immune Defic Syndr 75:382-390
Gonciulea, Anda; Wang, Ruibin; Althoff, Keri N et al. (2017) An Increased Rate of Fracture Occurs a Decade Earlier in HIV+ Compared to HIV- men in the Multicenter AIDS Cohort Study (MACS). AIDS :
Lake, Jordan E; Popov, Mikhail; Post, Wendy S et al. (2017) Visceral fat is associated with brain structure independent of human immunodeficiency virus infection status. J Neurovirol 23:385-393
Erlandson, Kristine M; Ng, Derek K; Jacobson, Lisa P et al. (2017) Inflammation, Immune Activation, Immunosenescence, and Hormonal Biomarkers in the Frailty-Related Phenotype of Men With or at Risk for HIV Infection. J Infect Dis 215:228-237
Price, Jennifer C; Wang, Ruibin; Seaberg, Eric C et al. (2017) The Association of Inflammatory Markers With Nonalcoholic Fatty Liver Disease Differs by Human Immunodeficiency Virus Serostatus. Open Forum Infect Dis 4:ofx153
Jiamsakul, Awachana; Kariminia, Azar; Althoff, Keri N et al. (2017) HIV Viral Load Suppression in Adults and Children Receiving Antiretroviral Therapy-Results From the IeDEA Collaboration. J Acquir Immune Defic Syndr 76:319-329
Dutta, Anupriya; Uno, Hajime; Holman, Alex et al. (2017) Racial differences in prostate cancer risk in young HIV-positive and HIV-negative men: a prospective cohort study. Cancer Causes Control 28:767-777
Monroe, A K; Zhang, L; Jacobson, L P et al. (2017) The association between physical activity and cognition in men with and without HIV infection. HIV Med 18:555-563

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