# A Randomized Trial to Optimize Skeletal Muscle while Reducing Adiposity in Veterans with HIV.

> **NIH VA I01** · VETERANS HEALTH ADMINISTRATION · 2024 · —

## Abstract

The Department of Veterans Affairs is the largest single provider of medical care to people with HIV in the United
States. With the advances achieved in antiretroviral therapy (ART), Veterans with HIV now survive decades.
However, this success is tempered by the rising burden of obesity now affecting 78% of Veterans. Defects in
adipose tissue lipid storage and regulation are hallmarks of both treated HIV and obesity, which leads to a high
degree of ectopic fat infiltrating organs and tissues such as skeletal muscle. The condition of excess lipid within
and around muscle, termed myosteatosis, predisposes Veterans to physical function decline, frailty, disability,
and cardiometabolic diseases such as diabetes and cardiovascular disease. In our current Merit supported
cohort, we found that 36% of Veterans with treated HIV have myosteatotic type obesity. Further, we found that
high ectopic fat accumulation in muscle (quantified by CT imaging of skeletal muscle density) is associated with
reduced mitochondrial oxidative capacity, greater inflammation, and impaired muscle glucose tolerance and
insulin sensitivity. Hence the quality of muscle is just as important as the quantity of muscle. However, this
important phenomenon has received little attention, especially in Veterans with HIV. Indeed, the need to target
mobilizing and metabolizing skeletal muscle ectopic fat while preserving/increasing the total amount of skeletal
muscle is most often overlooked and represents a major research gap and unmet clinical need. From our current
Merit Award funded study, we have an established collaboration of experienced VA researchers with expertise
in HIV and immunology, human nutrition and metabolism, endocrinology, radiology and imaging science, and
muscle physiology. Based on our findings, we have designed a multipronged integrated intervention that
combines: 1) dietary replacement of saturated with unsaturated fats; 2) coadministration of L-carnitine and
omega-3 fatty acid supplementation; and 3) targeted resistance exercise training. This evidence-based
intervention is designed to: a) increase lipid flux by facilitating the transfer of long-chain fatty acids into muscle
mitochondria for β-oxidation; b) decrease muscle proteolysis; and c) lessen insulin resistance and inflammation.
Using a randomized crossover placebo-matched trial design in a cohort of 47 Veterans who have HIV and
obesity, this study will determine the effects of the multi-pronged integrated intervention on: skeletal muscle
density, mitochondrial oxidative capacity, and fatty acid oxidation (Aim 1); glucose tolerance, insulin sensitivity,
and inflammation (Aim 2); and cardiopulmonary exercise tolerance and physical function (Aim 3). Obesity in
Veterans with treated HIV is a heterogeneous condition. Our current Merit research shows myosteatotic obesity
is a distinct condition from visceral or sarcopenic obesity, affected by different clinical factors. Our findings to
date provide the foundatio...

## Key facts

- **NIH application ID:** 11047485
- **Project number:** 2I01CX001930-06
- **Recipient organization:** VETERANS HEALTH ADMINISTRATION
- **Principal Investigator:** John Koethe
- **Activity code:** I01 (R01, R21, SBIR, etc.)
- **Funding institute:** VA
- **Fiscal year:** 2024
- **Award amount:** —
- **Award type:** 2
- **Project period:** 2020-01-01 → 2025-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/11047485

## Citation

> US National Institutes of Health, RePORTER application 11047485, A Randomized Trial to Optimize Skeletal Muscle while Reducing Adiposity in Veterans with HIV. (2I01CX001930-06). Retrieved via AI Analytics 2026-06-14 from https://api.ai-analytics.org/grant/nih/11047485. Licensed CC0.

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