TMAO – St. PETER HIV- Alcohol, Protein, Biomarkers, and Cardiovascular Disease Risk


Principal Investigators

Jeffrey Samet, MD, MA, MPH – Boston Medical Center

Matthew Freiberg, MD, MSc – Vanderbilt University Medical Center

Dmitry Lioznov, MD, PhD – First St. Petersburg Pavlov State Medical University

Key Personnel

Elena Blokhina, MD, PhD, Co-Investigator

Evgeny Krupitsky, MD, PhD, DMSci, Co-Investigator

Tatiana Yaroslavtseva, MD, Co-Investigator

Kaku So-Armah, PhD, Co-Investigator

Debbie Cheng, ScD, Co-Investigator, Biotatistician

Project Manager

Natalia Gnatienko, MPH


Vladimir Palatkin, MD – Russian Project Manager

Sally Bendiks, MPH – Research Project Manager

Ve Truong – Research Project Manager

Sarah Rossi – Senior Research Assistant

Grant Abstract

Heavy alcohol use among human immunodeficiency virus infected (HIV+) people is common and associated with heart failure (HF) and coronary heart disease (CHD). An unexplored potential mechanism for this association involves changes in intestinal microbes. These changes result in an altered state in the intestines called dysbiosis. Dysbiosis occurs with heavy alcohol use or HIV infection. Dysbiosis may shift the balance of microbial genomes (microbiomes) to promote increased trimethylamine N-oxide (TMAO) production. TMAO is a metabolite that requires intestinal microbes for its production. Increased TMAO is associated with cardiovascular disease (CVD) events, including subclinical CHD and HF morbidity and mortality in the general population. Yet, no published studies have assessed the link between alcohol and TMAO or TMAO and subclinical HF among HIV+ people. We hypothesize that among HIV+ heavy drinkers, alcohol use is associated with higher levels of TMAO, and that higher TMAO levels are associated with subclinical measures and biomarkers of HF. We will test these hypotheses in ST. PETER HIV – CVD, an observational study that will be built on and complement St. PETER HIV (H-35288), a randomized clinical trial (U01AA020780; begins enrollment Spring 2017).

In ST. PETER HIV – CVD, we propose to obtain at baseline and 3 months the following new data that will not otherwise have been obtained in St. PETER HIV: TMAO, echocardiography, B-type natriuretic peptide (BNP; biomarker of ventricular stretching), phosphatidylethanol (PEth; alcohol biomarker) and food frequency questionnaires. Echocardiography will be also be performed at 6 months.

If confirmed, our hypotheses will identify a biomarker (TMAO) responsive to interventions that reduce alcohol-related CVD risk in HIV+ heavy drinkers. Because heavy alcohol use interventions do not succeed in all, developing new alcohol treatment strategies that reduce alcohol’s negative health impact among HIV+ people are needed. The identification of biomarkers and the pathways they represent (e.g., dysbiosis) could result in new targets for intervention studies and improve CVD risk prediction in HIV+ drinkers.

URBAN ARCH Consortium website