Heavy alcohol (ETOH) use affects both liver and brain. Its effects on brain may be aggravated by associated hepatic and metabolic disturbances, including insulin resistance, oxidative stress, and mitochondrial dysfunction. The proposed study will investigate effects of ETOH consumption on HIV-associated brain dysfunction. The study incorporates state-of-the-art brain imaging methods along with clinical and laboratory methods to assess interactive effects of HIV infection, ETOH consumption, and hepatic dysfunction. We will examine how neurocognitive outcome and structural brain changes vary as a function of ETOH consumption, the extent of specific metabolic disturbances, and HIV-associated factors. A longitudinal experimental design will be employed with statistical modeling methods to characterize changes over time. Recent data from our laboratory point to alcohol-associated effects of HIV in the brain, including evidence that people who consume large quantities of ETOH have greater deficits at baseline and greater change over time than non users. Furthermore, our data suggest that basal ganglia, hippocampal, and cortical volume loss occur at an accelerated rate as a function of the interaction of these factors. Diffusion tensor imagining (DTI) data provide evidence of reduced structural integrity of subcortical systems that appears to be evident prior to development of structural changes on traditional MRI. Magnetic resonance spectroscopy (MRS) findings point to both increased brain metabolite levels reflecting inflammatory processes and also neuronal damage, particularly in the basal ganglia, but also in white matter and cortical areas. These abnormalities in the brain have been linked to both HIV and ETOH, though how these two factors interact over time to cause changes in brain structure and function is not well understood. The proposed study will compare HIV-infected and seronegative control patients who have been stratified into three groups based oh their ETOH use (Heavy ETOH use, moderate ETOH use, no-ETOH) who are assessed over 36 months on neurocognitive, neuroimaging, and laboratory measures. All will undergo laboratory testing including assessment of CD4, viral load, activated macrophages from plasma and CSF, and measures of liver, insulin, and metabolic function. Neuroimaging, laboratory, and neurocognitive assessment will be conducted at baseline, 12 and 36 months. Results will inform us about the interaction of ETOH and HIV in the brain, and provide metrics for assessing structural and metabolic brain changes, potentially extending the clinical application ofthese methods for brain disorders that may lead to neurodiagnostic advances for patients with HIV, including methods for dissociating effects of HIV from other co-morbid factors, most notably ETOH consumption and liver disease.

Public Health Relevance

This study will characterize the mechanisms by which the interaction of chronic alcohol exposure and HIV infection lead to neurodegeneration. In addition, this research will confirm the utility of peripheral biomarkers for identifying individuals at risk for developing ethanol/HAART-mediated leukoencephalopathy and neurodegeneration, and provide a rationale for counseling individuals to either substantially reduce or abstain from ethanol consumption while being treated with HAART. Greater understanding ofthe brain dysfunction stemming from alcohol use or abuse in conjunction with HIV in the context of HAART may help prevent the neurocognitive dysfunction that lead to high risk behaviors and also contribute to improved health status and qualitv of life.

National Institute of Health (NIH)
National Institute on Alcohol Abuse and Alcoholism (NIAAA)
Research Program Projects (P01)
Project #
Application #
Study Section
Special Emphasis Panel (ZAA1-BB (93))
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
Brown University
United States
Zip Code
Wray, Tyler B; Chan, Philip A; Celio, Mark A et al. (2017) HIV Testing Among Men Who Have Sex with Men in the Northeastern United States. AIDS Behav :
Szymkowicz, Sarah M; Dotson, Vonetta M; McLaren, Molly E et al. (2017) Precuneus abnormalities in middle-aged to older adults with depressive symptoms: An analysis of BDI-II symptom dimensions. Psychiatry Res 268:9-14
Kahler, Christopher W; Liu, Tao; Cioe, Patricia A et al. (2017) Direct and Indirect Effects of Heavy Alcohol Use on Clinical Outcomes in a Longitudinal Study of HIV Patients on ART. AIDS Behav 21:1825-1835
Nunn, Amy; Brinkley-Rubinstein, Lauren; Rose, Jennifer et al. (2017) Latent class analysis of acceptability and willingness to pay for self-HIV testing in a United States urban neighbourhood with high rates of HIV infection. J Int AIDS Soc 20:21290
White, Tara L (2017) Beyond Sensation Seeking: A Conceptual Framework for Individual Differences in Psychostimulant Drug Effects in Healthy Humans. Curr Opin Behav Sci 13:63-70
Thompson, Paul M; Andreassen, Ole A; Arias-Vasquez, Alejandro et al. (2017) ENIGMA and the individual: Predicting factors that affect the brain in 35 countries worldwide. Neuroimage 145:389-408
Sileo, Katelyn M; Kintu, Michael; Kiene, Susan M (2017) The intersection of intimate partner violence and HIV risk among women engaging in transactional sex in Ugandan fishing villages. AIDS Care :1-9
Marshall, Brandon D L; Tate, Janet P; McGinnis, Kathleen A et al. (2017) Long-term alcohol use patterns and HIV disease severity. AIDS 31:1313-1321
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 :
Clark, Uraina S; Sweet, Lawrence H; Morgello, Susan et al. (2017) High early life stress and aberrant amygdala activity: risk factors for elevated neuropsychiatric symptoms in HIV+ adults. Brain Imaging Behav 11:649-665

Showing the most recent 10 out of 91 publications