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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Cesar, Carina; Koethe, John R; Giganti, Mark J et al. (2016) Health outcomes among HIV-positive Latinos initiating antiretroviral therapy in North America versus Central and South America. J Int AIDS Soc 19:20684
Jotwani, Vasantha; Scherzer, Rebecca; Estrella, Michelle M et al. (2016) Brief Report: Cumulative Tenofovir Disoproxil Fumarate Exposure is Associated With Biomarkers of Tubular Injury and Fibrosis in HIV-Infected Men. J Acquir Immune Defic Syndr 73:177-81
Rachlis, Beth; Karwa, Rakhi; Chema, Celia et al. (2016) Targeted Spontaneous Reporting: Assessing Opportunities to Conduct Routine Pharmacovigilance for Antiretroviral Treatment on an International Scale. Drug Saf 39:959-76
Martinez-Picado, Javier; McLaren, Paul J; Erkizia, Itziar et al. (2016) Identification of Siglec-1 null individuals infected with HIV-1. Nat Commun 7:12412
Friedman, M Reuel; Coulter, Robert W S; Silvestre, Anthony J et al. (2016) Someone to count on: social support as an effect modifier of viral load suppression in a prospective cohort study. AIDS Care :1-12
Horvath, Steve; Gurven, Michael; Levine, Morgan E et al. (2016) An epigenetic clock analysis of race/ethnicity, sex, and coronary heart disease. Genome Biol 17:171
Buchacz, Kate; Lau, Bryan; Jing, Yuezhou et al. (2016) Incidence of AIDS-Defining Opportunistic Infections in a Multicohort Analysis of HIV-infected Persons in the United States and Canada, 2000-2010. J Infect Dis 214:862-72
Wada, Nikolas I; Bream, Jay H; Martínez-Maza, Otoniel et al. (2016) Inflammatory Biomarkers and Mortality Risk Among HIV-Suppressed Men: A Multisite Prospective Cohort Study. Clin Infect Dis 63:984-90
Akhtar-Khaleel, Wajiha Z; Cook, Robert L; Shoptaw, Steven et al. (2016) Trends and Predictors of Cigarette Smoking Among HIV Seropositive and Seronegative Men: The Multicenter Aids Cohort Study. AIDS Behav 20:622-32
Koethe, John R; Jenkins, Cathy A; Lau, Bryan et al. (2016) Rising Obesity Prevalence and Weight Gain Among Adults Starting Antiretroviral Therapy in the United States and Canada. AIDS Res Hum Retroviruses 32:50-8

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