# Myocardial Fibrosis and Steatosis Burden and Region-Specific Predictors of Progression among ART-treated Women with HIV infection in sub-Saharan Africa (The MUTIMA Study)

> **NIH NIH R01** · UNIVERSITY OF WASHINGTON · 2024 · $743,216

## Abstract

Project Summary/Abstract
Heart failure (HF) is a major barrier to healthy aging among people with HIV (PWH) in sub-Saharan Africa
(SSA). Women with HIV (WWH) may be most vulnerable, with a nearly two-fold increased risk for HIV-
attributable HF among women vs. men. Why HIV-attributable HF risk is higher in women is incompletely
understood, but among WWH, chronic inflammation, metabolic factors such as obesity, and other hormonal
factors such as accelerated reproductive aging are hypothesized to play key roles. Once HF is established
among PWH, the 1-year mortality rate is 31% and sudden cardiac death (SCD) from ventricular arrhythmias is
common. In this context, strong imperatives exist to identify strategies to prevent the development of HF and
SCD among WWH. The most important pathologic processes upstream of HF and SCD are myocardial
fibrosis and myocardial steatosis. Cardiovascular magnetic resonance (CMR) and spectroscopy (MRS) are
considered gold-standard techniques for identifying myocardial tissue characteristics, including diffuse
interstitial fibrosis, focal scar, and steatosis. Among PWH, myocardial fibrosis and steatosis correlate with
diastolic dysfunction; in addition, myocardial fibrosis predicts adverse cardiovascular outcomes and SCD. To
date, no studies have characterized the extent of myocardial fibrosis and steatosis among ART-treated WWH
in SSA or examined predictors of fibrosis/steatosis progression specific to this group. Through this innovative
proposal focus on WWH in SSA, we will: 1) characterize myocardial fibrosis burden and identify novel
infectious/immunologic predictors of progression; and 2) quantify myocardial steatosis burden and identify
hormonal/metabolic predictors of progression. We hypothesize that among WWH in SSA, predictors of
myocardial fibrosis progression will include endemic co-infections (e.g. cytomegalovirus and latent
tuberculosis), immune activation/inflammation indices (e.g. osteopontin and circulating immune cell subsets),
and novel metabolomic signatures. We further hypothesize that among this group, predictors of myocardial
steatosis progression will include reduced ovarian reserve (anteceding overt menopause; characterized by
menstrual history and levels of anti-Mullerian hormone), obesity and/or increased fat in ectopic depots (visceral
and epicardial fat by MRI), longer cumulative exposure to select ART subtypes including integrase inhibitors,
and novel metabolomic and lipidomic signatures (some overlapping with and some distinct from the signatures
associated with fibrosis). This work will inform the design of HF prevention strategies targeting: select
immune/inflammatory pathways (e.g. dual CCR2/CCR5 antagonism); vs. viral co-infections (e.g. letermovir for
treatment of cytomegalovirus); vs. early/abrupt decrement in endogenous estrogen production (e.g.
transdermal estrogen); vs. ART-associated weight gain (e.g. culturally-specific diet/exercise intervention timed
to initiation of or swit...

## Key facts

- **NIH application ID:** 10900822
- **Project number:** 5R01HL167645-02
- **Recipient organization:** UNIVERSITY OF WASHINGTON
- **Principal Investigator:** Chris Todd Longenecker
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $743,216
- **Award type:** 5
- **Project period:** 2023-08-07 → 2027-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10900822

## Citation

> US National Institutes of Health, RePORTER application 10900822, Myocardial Fibrosis and Steatosis Burden and Region-Specific Predictors of Progression among ART-treated Women with HIV infection in sub-Saharan Africa (The MUTIMA Study) (5R01HL167645-02). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10900822. Licensed CC0.

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