# 1/2 Alcohol Associated Comorbidities and Microbiome Evaluation in HIV (ACME HIV)

> **NIH NIH U01** · VANDERBILT UNIVERSITY MEDICAL CENTER · 2020 · $651,512

## Abstract

HIV infected (HIV+) heavy drinkers are at risk for cardiovascular diseases (CVD) via myriad pathways. Heavy
alcohol use causes microbial translocation (MT) and inflammation. Additionally, alcohol-related changes in the
GI tract microbiome—termed dysbiosis—are central to this pro-inflammatory cascade and could serve as novel
therapeutic targets for reducing CVD risk among HIV+ heavy drinkers. Alcohol-associated dysbiosis is
characterized by a loss of gut bacterial biodiversity, a reduction in “beneficial” bacteria, and/or an expansion of
harmful or “pro-inflammatory” bacteria (e.g., those which produce trimethylamine N-oxide (TMAO), a
metabolite associated with increased CVD risk). While murine models show alcohol associated dysbiosis was
attenuated by probiotics even in the presence of continued alcohol consumption, there remains insufficient
knowledge to identify a therapeutic target in humans for two reasons: 1) most studies involve murine models;
and 2) scant human studies have small sample sizes with few HIV+ participants, and lack longitudinal
assessment of alcohol intake, inflammation, and CVD risk in relation to the GI microbiome. This application
addresses these gaps. We hypothesize that alcohol-associated dysbiosis will: (1) be greater in HIV+ very
heavy drinkers (AUDIT score≥20) vs. heavy drinkers (AUDIT<20); (2) increase biomarker levels of intestinal
permeability (e.g., intestinal fatty acid binding protein (IFABP), MT (e.g., endotoxin), inflammation (interleukin
6) and TMAO; and (3) increase serum biomarkers for and alter echocardiographic (Echo) measures of cardiac
function (N-terminal pro Brain Naturetic Peptide, NT pro-BNP, and left ventricular ejection fraction, LVEF,
respectively). To test these hypotheses, we will enroll 200 HIV+ participants from St. PETER HIV, a funded
RCT using pharmacotherapy to reduce alcohol use, smoking, inflammation, and CVD risk. This application,
Alcohol-associated CVD and Microbiome Evaluation Study (ACME HIV 1/2) leverages existing resources of St.
PETER HIV: participant recruitment, measures of alcohol consumption, biospecimen and biomarker collection;
expertise in alcohol, HIV, CVD, and microbial genomics. New data include: fecal samples to characterize the
GI microbiome, serum biomarkers, and echo measures. In response to RFA-AA-17-014, we will partner with
the Southern HIV & Alcohol Research Consortium (SHARC, ACME HIV 2/2) to corroborate our findings in
Aims 1 and 2 and to conduct combined cross-cohort analyses. We will complete the following SPECIFIC AIMS
among HIV+ heavy drinkers: AIM 1: To assess longitudinal qualitative and quantitative changes in the gut
microbiome (dysbiosis) associated with very heavy alcohol consumption. AIM 2: To determine the effect of
dysbiosis on intestinal permeability, MT, inflammation, and TMAO levels. AIM 3: To investigate the impact of
dysbiosis on biomarkers for and echo measures of cardiac structure and function. Completion of these aims
will lay groundwork f...

## Key facts

- **NIH application ID:** 9985671
- **Project number:** 5U01AA026222-04
- **Recipient organization:** VANDERBILT UNIVERSITY MEDICAL CENTER
- **Principal Investigator:** SHIRISH S BARVE
- **Activity code:** U01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $651,512
- **Award type:** 5
- **Project period:** 2017-08-01 → 2022-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9985671

## Citation

> US National Institutes of Health, RePORTER application 9985671, 1/2 Alcohol Associated Comorbidities and Microbiome Evaluation in HIV (ACME HIV) (5U01AA026222-04). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9985671. Licensed CC0.

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