# Mechanisms of Cardiac Dysfunction in HIV and the Effect of Statins

> **NIH NIH R01** · MASSACHUSETTS GENERAL HOSPITAL · 2020 · $659,315

## Abstract

7. Project Summary/Abstract
Contemporary cohorts of people living with HIV (PLWH) have a ~ 2.5-fold increased relative risk of heart failure
versus matched controls. The predominant type of heart failure among PLWH is heart failure with a preserved
ejection fraction (HFpEF). This type of heart failure is typically preceded by diastolic dysfunction, a condition in
which the left ventricle of the heart stiffens, resulting in delayed relaxation and increased filling pressures.
Among PLWH, the prevalence of diastolic dysfunction is strikingly high: 43%. Once diastolic dysfunction has
progressed to overt HFpEF, no good therapeutic options exist. Thus, strong imperatives exist to test rational,
safe strategies which may preserve diastolic function and prevent progression to overt heart failure among
aging PLWH on ART. There are two key processes which likely contribute to the development of diastolic
dysfunction in HIV. The first is myocardial fibrosis, a condition in which excess collagen is deposited in the
myocardial structural space. The second is myocardial steatosis, a condition in which triglycerides are
ectopically deposited within cardiomyocytes. Myocardial fibrosis and myocardial steatosis are both increased
among PLWH, in relation to diastolic dysfunction. We postulate that PLWH without overt heart failure, statin
therapy will reduce the progression of myocardial fibrosis and myocardial steatosis, preserving cardiac
function. Our primary hypothesis is that statin effects to dampen systemic immune activation and inflammation
will translate to reduced in situ myocardial inflammation and, in turn, reduced myocardial fibrosis. We will also
test an alternate hypothesis that statin effects to improve lipid metabolism will result in reduced ectopic fat
deposition in the heart. Cardiac magnetic resonance imaging/magnetic resonance spectroscopy (MRI/MRS)
represents a gold-standard approach with which to test our hypotheses. We propose an observational cardiac
MRI/MRS-based study, CARDIAC-MR, integrated with an ongoing randomized trial of pitavastatin vs. placebo
(REPRIEVE). From 8 REPRIEVE sites, we will co-enroll 130 PLWH aged 40-75 without known heart failure.
Outside of REPRIEVE, we will orchestrate additional study visits at entry and 24 months. At these visits,
participants will undergo cardiac MRI/MRS, as well as targeted metabolic and immune phenotyping. Our work
will answer scientific questions relevant to heart failure prevention in HIV which will not otherwise be addressed
in REPRIEVE. If we confirm our hypothesis that statins forestall progression of myocardial fibrosis and/or fat
among PLWH, we will have found the first effective strategy to preserve cardiac function in HIV. Even in the
case of null statin effects on fibrosis/fat, our baseline characterization of pathologic pathways predisposing to
cardiac dysfunction will help identify future targeted strategies geared toward heart failure prevention in HIV.
Given that heart failure is a...

## Key facts

- **NIH application ID:** 9906261
- **Project number:** 5R01HL137562-04
- **Recipient organization:** MASSACHUSETTS GENERAL HOSPITAL
- **Principal Investigator:** Tomas G Neilan
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $659,315
- **Award type:** 5
- **Project period:** 2017-07-01 → 2024-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9906261

## Citation

> US National Institutes of Health, RePORTER application 9906261, Mechanisms of Cardiac Dysfunction in HIV and the Effect of Statins (5R01HL137562-04). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9906261. Licensed CC0.

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