# Cardiac Energetics, Diastolic Dysfunction and Exercise Intolerance in PLWH

> **NIH NIH R56** · JOHNS HOPKINS UNIVERSITY · 2021 · $605,723

## Abstract

People living with HIV infection (PLWH) are living longer but experience accelerated functional decline,
which can be manifested as increased exercise-associated fatigue and dyspnea as compared to non-infected
individuals. Functional decline is associated with impaired quality of life, increased vulnerability to superimposed
stresses, and the likelihood of premature morbidity and mortality. The responsible mechanisms, however, are
poorly understood. Considerable pre-clinical data and our pilot clinical studies using 31P magnetic resonance
spectroscopy (MRS) suggest an “energetic myopathy” as a possible basis for the fatigue and decreased
performance in older PLWH individuals. In addition, inflammation impairs mitochondrial function and is increased
with advanced age per se, as well as in combined ART treated and viral-suppressed PLWH. Altered cardiac
metabolism and performance may also contribute to exercise intolerance and this study proposes examination
of cardiac high energy phosphate metabolism, its causes and the consequences for left ventricular diastolic
dysfunction (DD) in PLWH. The central hypothesis of this study is that impaired cardiac mitochondrial energy
metabolism contributes to diastolic dysfunction and to exercise intolerance in PLWH. The specific aims are 1) to
define the scope and extent of myocardial energetic abnormalities at rest and exercise using 31P MRS/MRI in
PLWH, 2) to probe the factors underlying cardiac muscle mitochondrial and energetic abnormalities in PLWH,
including factors unique to PLWH (ART history and cumulative viral history) and others more common in PLWH
(increased inflammation, immune activation, insulin resistance, and/or higher cardiac muscle lipids by MRI), and
3) to determine the functional significance of observed cardiac muscle energetic changes in PLWH for DD and,
in turn, for EI. The studies will leverage expertise, resources, and established PLWH cohorts at Johns Hopkins
and collect novel cardiac energetic, diastolic function, quantitative exercise tolerance and biomarker data. This
proposal will deliver novel understanding of the type and extent of myocardial energetic-mitochondrial
abnormalities in PLWH, the factors prevalent in PLWH that are most closely related to such cardiac
mitochondrial-energetic changes, and the functional impact on diastolic dysfunction and, in turn, exercise
intolerance. These studies, characterizing the presence and functional consequences of what appears to be a
“mitochondriopathy” of cardiac and skeletal muscle of PLWH promise new avenues to better understand the
problem and to design metabolic strategies to reduce the personal and societal impact of HIV disease-related
functional decline in this important and growing population.

## Key facts

- **NIH application ID:** 10479415
- **Project number:** 1R56HL156703-01A1
- **Recipient organization:** JOHNS HOPKINS UNIVERSITY
- **Principal Investigator:** ROBERT G WEISS
- **Activity code:** R56 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $605,723
- **Award type:** 1
- **Project period:** 2021-09-21 → 2023-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10479415

## Citation

> US National Institutes of Health, RePORTER application 10479415, Cardiac Energetics, Diastolic Dysfunction and Exercise Intolerance in PLWH (1R56HL156703-01A1). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10479415. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*