Effects of experimentally-induced reductions in alcohol consumption on brain cognitive, and clinical outcomes and motivation for changing drinking in older persons with HIV infection

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This proposed U01 study will build on our past findings to determine the extent to which marked reductions in alcohol consumption over 4-weeks via contingency management (CM) improves cognitive performance, brain functions and pathophysiology, and HIV-associated health outcomes. HIV-associated neurocognitive dysfunction continues even with antiretroviral treatment, and even mild cognitive impairment is associated with detrimental health outcomes in older HIV+ adults. Alcohol consumption may affect the brain directly or indirectly via liver toxicity and systemic inflammation. Our past findings indicate that current heavy alcohol use is more strongly associated with cognitive/brain dysfunction among HIV+ adults than lifetime consumption, suggesting that these effects may be reversible with reductions in drinking. Towards this objective, we propose to enroll 180 HIV+ adults with heavy drinking, and then use CM with financial incentives and a wearable alcohol biosensor to maximally reduce alcohol consumption from baseline (T1) to 4-weeks later (T2). We will then conduct a motivational interview to determine perceived benefits and obstacles to drinking reduction, and conduct a final assessment 1 year later (T3), at which point persons may or may not have resumed heavy drinking. We will conduct state-of-the-art neuroimaging, cognitive, and behavioral assessments at each timepoint, and then continue to track long-term drinking and HIV outcomes in our companion Cohort (U24). The Specific Aims of this proposal are: 1) to demonstrate improved cognitive performance and brain function (fMRI) after 4-weeks of CM-induced alcohol reduction among HIV+ adults, followed by worsening of these effects 1-year later if heavy drinking resumes; 2) to demonstrate that cerebral metabolic (MRS) and neuroinflammatory (DTI-free water) markers will also improve with CM-induced alcohol reduction and worsen if drinking resumes post-CM; and 3) Determine whether perceived benefits and challenges to drinking reduction identified during motivational interviewing (MI) predict drinking reductions or relapse one-year post-CM. We will also determine whether changes in cerebral pathophysiology (MRS, DTI-FW) correspond with changes in cognition, brain function (fMRI) and serum inflammatory and liver biomarkers. In addition, we will determine which neuroimaging and baseline clinical factors are associated with long-term drinking and clinical outcomes (e.g. HIV viral suppression, liver comorbidities). In the context of this study, CM and MI are being employed as an experimental manipulation and data collection opportunity, respectively, rather than as clinical interventions per se. The A-B-A design will enable us to clearly identify whether alcohol effects on cognition and the brain are reversible, and to identify optimal strategies to promote short-term and long-term alcohol reduction in HIV+ adults. This U01 project is closely linked to the Administrative U24 (SHARC), which supports the Florida Cohort that is the source of potential participants for this study, and our Behavioral Science and Biostatistics Core (U24) that will help implement and monitor the CM, MI, and alcohol biosensor procedures.