Combination antiretroviral therapy (cART) has transformed HIV into a complex chronic disease but does not fully restore health. Although the reasons for this fact are not clear, likely causes include chronic immune activation, alcohol use, and multimorbidity. Even when HIV infection is suppressed, it is associated with chronic activation of the immune system. Alcohol use and multimorbidity are common among those aging with HIV infection (HIV+) and they lead to immune activation. Chronic immune activation is associated with immune dysfunction, organ system injury, and death. HIV, alcohol use, multimorbidity and polypharmacy resulting from HIV and multimorbidity can cause direct organ system injury. To better understand this process we propose to enroll 200 HIV infected cART (and antiretroviral) naive individuals and 100 uninfected individuals (HIV-) from the Veterans Aging Cohort Study.
Our specific aims are to (1) collect and bank serial biospecimen samples among HIV+ individuals initiating cART and demographically and behaviorally similar uninfected comparators and to begin to use these samples to characterize (2) the longitudinal associations of alcohol use and multimorbidity on immune function and (3) alcohol use and polypharmacy on organ system injury as measured by the VACS index and its components. Among HIV+ we will collect specimens before and after cART initiation. We hypothesize that alcohol, multimorbidity, polypharmacy and immune dysfunction will be present in all age groups of both groups and that alcohol, multimorbidity, and polypharmacy will be associated with increasing immune dysfunction and end organ damage. Alcohol use will be assessed by self-report and phosphatidyl ethanol.
These aims are critical if we are to understand how aging and alcohol use with HIV differs from aging and alcohol use among uninfected similar comparators. This work will help characterize immune dysfunction and organ system injury among aging individuals who drink alcohol. Lastly, these longitudinal specimens can be linked with adjudicated clinical outcomes and subclinical disease measures among HIV+ and demographically and behaviorally similar uninfected people to provide a unique and valuable resource for investigators within and outside the VACS community.

Public Health Relevance

We propose to examine whether changes in alcohol consumption, multimorbidity, and polypharmacy are associated with changes in immune dysfunction and mortality risk among HIV+ and matched uninfected people. As part of this study we will be storing specimens that can be used for future studies with other research collaborators to maximize the utility of these specimens for scientific discovery

National Institute of Health (NIH)
National Institute on Alcohol Abuse and Alcoholism (NIAAA)
Resource-Related Research Projects--Cooperative Agreements (U24)
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Special Emphasis Panel (ZAA1-DD (10))
Program Officer
Roach, Deidra
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Yale University
Internal Medicine/Medicine
Schools of Medicine
New Haven
United States
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Hawkins, Kellie L; Gordon, Kirsha S; Levin, Myron J et al. (2018) Herpes Zoster and Herpes Zoster Vaccine Rates Among Adults Living With and Without HIV in the Veterans Aging Cohort Study. J Acquir Immune Defic Syndr 79:527-533
Justice, Amy C; Gordon, Kirsha S; Skanderson, Melissa et al. (2018) Nonantiretroviral polypharmacy and adverse health outcomes among HIV-infected and uninfected individuals. AIDS 32:739-749
Li, Haifeng; Su, Linnan; Chen, Sheng et al. (2018) Physicochemical Characterization and Functional Analysis of the Polysaccharide from the Edible Microalga Nostoc sphaeroides. Molecules 23:
Khan, Maria R; McGinnis, Kathleen A; Grov, Christian et al. (2018) Past year and prior incarceration and HIV transmission risk among HIV-positive men who have sex with men in the US. AIDS Care :1-8
Justice, Amy C; Gordon, Kirsha; Skanderson, Melissa et al. (2018) Non antiretroviral polypharmacy and adverse health outcomes among HIV-infected and uninfected individuals. AIDS :
Rajeevan, Nallakkandi; Niehoff, Kristina M; Charpentier, Peter et al. (2017) Utilizing patient data from the veterans administration electronic health record to support web-based clinical decision support: informatics challenges and issues from three clinical domains. BMC Med Inform Decis Mak 17:111
Greene, Meredith; Justice, Amy C; Covinsky, Kenneth E (2017) Assessment of geriatric syndromes and physical function in people living with HIV. Virulence 8:586-598
Marshall, Brandon David Lewis; Tate, Janet P; Mcginnis, Kathleen A et al. (2017) Long-term alcohol use patterns and HIV disease severity: A joint trajectory analysis. AIDS :
Li, Haifeng; Han, Wenjing; Wang, Hongyu et al. (2017) Tanshinone IIA Inhibits Glutamate-Induced Oxidative Toxicity through Prevention of Mitochondrial Dysfunction and Suppression of MAPK Activation in SH-SY5Y Human Neuroblastoma Cells. Oxid Med Cell Longev 2017:4517486
Li, Haifeng; Shi, Ruona; Ding, Fei et al. (2016) Astragalus Polysaccharide Suppresses 6-Hydroxydopamine-Induced Neurotoxicity in Caenorhabditis elegans. Oxid Med Cell Longev 2016:4856761

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