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.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project with Complex Structure Cooperative Agreement (UM1)
Project #
5UM1AI035043-25
Application #
9243908
Study Section
Special Emphasis Panel (ZAI1-NLE-A (J1))
Program Officer
Roe, Joanad'Arc C
Project Start
1993-04-01
Project End
2019-03-31
Budget Start
2017-04-19
Budget End
2018-03-31
Support Year
25
Fiscal Year
2017
Total Cost
$2,480,632
Indirect Cost
$951,237
Name
Johns Hopkins University
Department
Public Health & Prev Medicine
Type
Schools of Public Health
DUNS #
001910777
City
Baltimore
State
MD
Country
United States
Zip Code
21205
Dutta, Anupriya; Uno, Hajime; Lorenz, David R et al. (2018) Low T-cell subsets prior to development of virus-associated cancer in HIV-seronegative men who have sex with men. Cancer Causes Control 29:1131-1142
Martin, Maureen P; Naranbhai, Vivek; Shea, Patrick R et al. (2018) Killer cell immunoglobulin-like receptor 3DL1 variation modifies HLA-B*57 protection against HIV-1. J Clin Invest 128:1903-1912
Yanik, Elizabeth L; Hernández-Ramírez, Raúl U; Qin, Li et al. (2018) Brief Report: Cutaneous Melanoma Risk Among People With HIV in the United States and Canada. J Acquir Immune Defic Syndr 78:499-504
Mellor-Crummey, Lauren E; Lake, Jordan E; Wilhalme, Holly et al. (2018) A Comparison of the Liver Fat Score and CT Liver-to-Spleen Ratio as Predictors of Fatty Liver Disease by HIV Serostatus. J Clin Gastroenterol Hepatol 2:
Adland, Emily; Hill, Matilda; Lavandier, Nora et al. (2018) Differential Immunodominance Hierarchy of CD8+ T-Cell Responses in HLA-B*27:05- and -B*27:02-Mediated Control of HIV-1 Infection. J Virol 92:
Altekruse, Sean F; Shiels, Meredith S; Modur, Sharada P et al. (2018) Cancer burden attributable to cigarette smoking among HIV-infected people in North America. AIDS 32:513-521
Irwin, Michael R; Archer, Gemma; Olmstead, Richard et al. (2018) Increased risk of depression in non-depressed HIV infected men with sleep disturbance: Prospective findings from the Multicenter AIDS Cohort Study. EBioMedicine 36:454-460
Guha, Debjani; Wagner, Marc C E; Ayyavoo, Velpandi (2018) Human immunodeficiency virus type 1 (HIV-1)-mediated neuroinflammation dysregulates neurogranin and induces synaptodendritic injury. J Neuroinflammation 15:126
Li, Yijia; Nouraie, Seyed Mehdi; Kessinger, Cathy et al. (2018) Factors Associated With Progression of Lung Function Abnormalities in HIV-Infected Individuals. J Acquir Immune Defic Syndr 79:501-509
Tipton, Laura; Cuenco, Karen T; Huang, Laurence et al. (2018) Measuring associations between the microbiota and repeated measures of continuous clinical variables using a lasso-penalized generalized linear mixed model. BioData Min 11:12

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