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

> **NIH NIH U01** · UNIVERSITY OF LOUISVILLE · 2021 · $577,674

## Abstract

Heavy alcohol drinking and HIV-1 infection are independently associated with the development of
abnormalities in the brain function and cognition, and increasing evidence indicates that the combinatorial
effects of HIV infection and alcohol are likely to worsen these abnormalities. Significantly, both HIV- 1 infection
and chronic alcohol abuse cause alterations in gut microbiome (dysbiosis) and increase intestinal permeability
and microbial translocation (MT) which are major pathogenic factors driving local and systemic inflammation.
The dysbiosis is characterized by loss of gut bacterial biodiversity, a reduction in beneficial bacteria, and/or an
expansion of harmful or pro-inflammatory bacteria. However, there is limited understanding of (i) the interactive
effects of heavy alcohol drinking and HIV-1 infection on gut dysbiosis and (ii) the longitudinal qualitative
(microbial membership) and quantitative (relevant abundance) determinants of dysbiosis. The current proposal
addresses these gaps with an overall goal to promote the development of rational therapies targeting gut
dysbiosis. Accordingly, we pursue a unifying hypothesis that in HIV-infected individuals, heavy alcohol use
compounds gut dysbiosis and consequent peripheral immune inflammation leading to exacerbation of neuro-
inflammation and cognitive dysfunction. To test these hypotheses, we will enroll 100 HIV+ participants from
“30-to-90-day challenge” Florida SHARC study (AA020797). This is a funded prospective cohort study in which
enrolled heavy drinkers are challenged to stop drinking for 30 to 90 days, assisted by contingency
management (CM) payments and motivational interviewing. This application, Alcohol associated
Comorbidities and Microbiome Evaluation in HIV (ACME HIV 2/2) leverages the existing resources of
“30-to-90-day challenge” Florida SHARC study: participant recruitment, measures of alcohol consumption,
biospecimen and biomarker collection; expertise in alcohol, HIV and neuroimaging. New data include:
longitudinal changes in gut dysbiosis, correlative changes in peripheral inflammation, and measures of
cognition and neuroinflammation. In response to RFA-AA-17-014, we will partner with the St. PETER HIV
study (ACME HIV 1/2) 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 impact of HIV infection and alcohol abuse induced gut dysbiosis
on intestinal permeability, microbial translocation (MT), and resultant peripheral endotoxemia, immune
activation and inflammation. AIM 3: To investigate the impact of dysbiosis and peripheral inflammation on
development of neuro-inflammation and cognitive function. Completion of these aims will lay groundwork for an
intervention targeting alcohol-associate...

## Key facts

- **NIH application ID:** 10246871
- **Project number:** 5U01AA026225-05
- **Recipient organization:** UNIVERSITY OF LOUISVILLE
- **Principal Investigator:** SHIRISH S BARVE
- **Activity code:** U01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $577,674
- **Award type:** 5
- **Project period:** 2017-09-22 → 2022-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10246871

## Citation

> US National Institutes of Health, RePORTER application 10246871, 2/2 Alcohol associated Comorbidities and Microbiome Evaluation in HIV (ACME HIV) (5U01AA026225-05). Retrieved via AI Analytics 2026-05-21 from https://api.ai-analytics.org/grant/nih/10246871. Licensed CC0.

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