Southeast Translational Alcohol and HIV Research Center (STAHR Center)

Vanderbilt University Medical Center, Nashville TN

Investigators

Abstract

People with HIV (PWH) have a two-fold excess risk of cardiovascular disease (CVD) as compared to those without HIV. Some of this excess risk is due to heavy alcohol consumption. Presently, few therapies exist that effectively reduce alcohol consumption or mitigate alcohol’s harmful effects. Our overarching objective and theme are to conduct clinical trials and observational studies that inform new clinical trials to reduce alcohol consumption or mitigate alcohol’s harmful effects among PWH who are at risk for CVD. Informed by our prior clinical trials and cohort studies, the Southeast Translational Alcohol and HIV Research (STAHR) Center proposes three inter-related projects focused on alcohol, gut dysbiosis and its derived metabolites, glucagon like peptide 1 (GLP-1), inflammation, and CVD risk among PWH. Project 1, GEM HIV, will examine the association between alcohol, gut dysbiosis and dysbiosis derived metabolites, biomarkers of inflammation, gut permeability, CVD risk and endogenous GLP-1 and determine whether a probiotic can increase endogenous GLP-1 levels among PWH who are heavy drinkers. Project 2, GUT CVD HIV, will determine the association between dysregulation of tryptophan catabolism and its metabolites (Kynurenine/Tryptophan, KYN/TRP ratio) and alcohol, senescent T cells, vascular inflammation, and CVD and whether a probiotic can reduce the KYN/TRP ratio, T cell senescence, and vascular inflammation among PWH who are heavy drinkers. Project 3, GL1DER HIV RCT, proposes a randomized clinical trial that will test whether a GLP-1 receptor agonist (semaglutide) versus placebo decreases alcohol consumption, cigarette smoking and CVD risk among PWH. This trial will be conducted at the Tennessee Center for AIDS Research at Vanderbilt University Medical Center (VUMC). Projects 1 and 2 will be ancillary studies to our ongoing META HIV CVD RCT (P01AA029542, PIs Freiberg, Barve). Project 2 will also use Veterans Aging Cohort Study (VACS) data. All projects will be supported by our Administrative (Admin) and Dissemination Cores at VUMC, and the Resource Core at the Norton Research Institute in conjunction with the Integrated Metagenomics and Metabolomics Core at the University of Louisville Alcohol Research Center which is part of the ongoing META HIV CVD RCT. The Admin Core will be responsible for coordinating all study projects and cores, and the Resource Core will provide a unified analytical platform to meet all the technical needs for the data acquisition, generation, management, analysis, and storage needs across the three projects. The Dissemination Core will connect the STAHR Center faculty, staff, and our research with (1) the global scientific community, (2) trainees and health care professionals and (3) the PWH community. IMPACT: This research will advance our understanding of alcohol’s effect on CVD among PWH. If our hypotheses are correct, endogenous GLP-1 and tryptophan metabolites may serve as targets for future RCTs designed to reduce alcohol’s harmful effects on CVD while GLP-1 receptor agonists may ultimately revolutionize care by reducing alcohol and CVD risk among PWH.