# Personalizing Risk from Alcohol among HIV+/-: Genetics, Medication Toxicity and PEth

> **NIH NIH P01** · YALE UNIVERSITY · 2023 · $281,651

## Abstract

HARP PROJECT 1 SUMMARY
Health risks associated with alcohol use in the context of polypharmacy (AP risks) are likely substantial,
particularly for people aging with HIV (PAH). Alcohol has known serious adverse interactions with many
commonly prescribed medications, including several antiretrovirals (ARVs). These interactive medications are
considered “potentially inappropriate medications” among those who drink (A-PIMs) and most PAH drink. They
also initiate polypharmacy (5+ medications) a decade earlier than uninfected individuals and both aging and
HIV reduce tolerance to the combined effects of alcohol and polypharmacy due to increased physiologic frailty.
AP risks are complex, interacting, and highly individual. They depend on the health outcome of interest, the
degree of physiologic frailty, the level of exposure to alcohol and polypharmacy, and underlying genetic liability.
Among PAH, risks for neuro-cognitive compromise and alcohol associated liver disease (AALD) likely increase
with any alcohol use in the context of polypharmacy and A-PIMs may be particularly problematic. Accounting
for physiologic frailty (VACS Index), using self-reported alcohol use (AUDIT-C) and employing multiple metrics
of polypharmacy (medication count, A-PIMS), we have begun to characterize AP risks associated with serious
falls, pneumonia, hospitalization, mortality and delirium. We now propose to extend this work among PAH and
uninfected individuals to include genetic liability and AP risk for AALD resulting in decompensated liver
cirrhosis (DLC), a critically important outcome given the hepatic metabolism of most medications, including
ARVs. Personalized medicine combines large-scale, real-world data, high-powered computing and data
analytics to summarize complex information on an individual level. Based on our prior work and in collaboration
with our extended expert network and Administrative/Data Analytic (ADA) Core, we will use data analytics to
develop personalized, accurate combined measure of AP risk for DLC and other patient outcomes considering
the role of physiologic frailty (VACS Index), A-PIMS, and genetic liability for pharmacogenomic interactions
(PGx-PIMS) (Aim 1). In Aim 2 we explore the role of genetic liability for unhealthy alcohol use by testing
whether a polygenic risk score (PRS) modifies AP risk or response to AUD treatment differentially by HIV
status. PRS from Aims 2 will inform further AP modeling (Aim 1) and evaluation of candidate repurposed
medications (Project 2, aims 1 and 2). Importantly, personalized AP risk must be effectively communicated to
optimize its impact on behavior change. Informed by our expert Risk Communication (Resource) Core (RCC),
we will implement personalized AP risk assessments in a series of theory-based Information-Motivation-
Behavioral Skills /Motivational Interviewing (IMB-MI) behavior change pilot studies to evaluate our approach
(Aim 3). Lessons learned will also be applied in pilots targeting PAH with al...

## Key facts

- **NIH application ID:** 10686386
- **Project number:** 5P01AA029545-03
- **Recipient organization:** YALE UNIVERSITY
- **Principal Investigator:** Amy Caroline Justice
- **Activity code:** P01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2023
- **Award amount:** $281,651
- **Award type:** 5
- **Project period:** 2021-09-10 → 2026-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10686386

## Citation

> US National Institutes of Health, RePORTER application 10686386, Personalizing Risk from Alcohol among HIV+/-: Genetics, Medication Toxicity and PEth (5P01AA029545-03). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10686386. Licensed CC0.

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