# Alcohol and Metabolic Dysregulation in PLWH: Mechanisms Underlying Risk for Comorbidities

> **NIH NIH P60** · LSU HEALTH SCIENCES CENTER · 2024 · $117,156

## Abstract

Abstract LSUHSC CARC Research Component 2:
Alcohol and Metabolic Dysregulation in PLWH: Mechanisms Underlying Risk for Comorbidities
Reduced mortality rates with antiretroviral therapy (ART) and increased survival of persons living with human
immunodeficiency virus (HIV) (PLWH), transformed HIV infection into a chronic disease that frequently coexists
with at-risk alcohol drinking. Increased longevity of PLWH is complicated with comorbidities that may be
exacerbated by at-risk alcohol consumption, unhealthy dietary behaviors, and ART adverse effects.
Compromised metabolic health is directly linked to greater risk for comorbidities afflicting PLWH and increases
progressively with time on ART. Data from our translational New Orleans Alcohol and HIV (NOAH) longitudinal
study of in-care PLWH show high prevalence of overweight, obesity, at-risk alcohol use, and poor dietary habits.
Subjects with at-risk alcohol use show greater incidence of impaired oral glucose tolerance. In addition, data
from chronic binge alcohol administered ART-treated simian immunodeficiency virus-infected nonhuman
primates (NHP) identified significant alterations in control (pancreas), effector (liver and adipose), and target
(muscle and bone) organ metabolic homeostatic mechanisms associated with impaired response to glucose
tolerance like that seen in the clinical setting. Collectively, published and preliminary clinical and preclinical data
collected by our team of investigators support the scientific premise that alcohol-induced early intestinal
pathogenesis promotes gut leak and immune activation promoting cellular energy metabolism dyshomeostasis.
We hypothesize metabolic dyshomeostasis underlies the increased risk for comorbidities in PLWH. Studies
proposed use a bidirectional translational approach to examine the mechanisms leading to metabolic instability
and how this is affected by at-risk alcohol consumption and consumption of a Western diet. The proposed
approach uses state-of-the-art techniques, combines in vivo with in vitro studies, and leverages our established
NHP model of HIV infection and the parallel NOAH clinical longitudinal study to examine the mechanisms
disrupted by alcohol in organs vital to the metabolic homeostatic axis in a virally-suppressed host. The expected
results will have a profound impact on identification of the underlying mechanisms of alcohol-associated
metabolic instability and will identify relevant targets for therapeutic interventions to ameliorate HIV/ART
associated metabolic derangements.

## Key facts

- **NIH application ID:** 10746441
- **Project number:** 5P60AA009803-31
- **Recipient organization:** LSU HEALTH SCIENCES CENTER
- **Principal Investigator:** PATRICIA E. MOLINA
- **Activity code:** P60 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $117,156
- **Award type:** 5
- **Project period:** 1996-12-01 → 2024-11-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10746441

## Citation

> US National Institutes of Health, RePORTER application 10746441, Alcohol and Metabolic Dysregulation in PLWH: Mechanisms Underlying Risk for Comorbidities (5P60AA009803-31). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10746441. Licensed CC0.

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