# Epigenetic dysregulation of inflammation linked to longitudinal cardiac toxicity in perinatal HIV infection

> **NIH NIH R21** · WEILL MEDICAL COLL OF CORNELL UNIV · 2022 · $285,826

## Abstract

Project Summary
This proposal will use archived longitudinal cardiac imaging data and blood biospecimens from the NIH
Pediatric HIV/AIDS Cohort Study (PHACS) to advance pediatric HIV/AIDS research by studying the interplay
between epigenetic dysfunction of disease-critical immune cell monocytes and longitudinal cardiac structure
and function in both perinatally infected adolescents and young adults living with HIV and HIV-exposed
uninfected (HEU) individuals. Increasing evidence shows that children who perinatally acquired HIV and have
been exposed to antiretroviral therapy (ART) throughout development have documented subclinical cardiac
abnormalities and an increased risk for cardiometabolic diseases. Systemic immune inflammation and
mitochondrial dysfunction have been linked to HIV/ART exposure and cardiac abnormalities in children living
with HIV. Yet, there remains a limited understanding of the biological mechanisms by which perinatal HIV
infection and longitudinal exposure to ART interact to alter immune cell function leading to progressive
deleterious cardiac changes. The novel premise of the proposed study is that early exposure to HIV and
longitudinal ART during childhood imprints a durable biological memory on the epigenome of proinflammatory
immune cells, as characterized by increased levels of systemic inflammation and mitochondrial dysfunction
related to progressive deleterious changes in left ventricular stress and cardiomyocyte damage. Using a
systems biology approach, we will examine epigenetic profiles of enriched monocyte cells obtained from viably
cryopreserved peripheral blood mononuclear cells (PBMCs) in 120 HIV+ adolescents and young adults with a
mean ART exposure of 11.3 years and 80 HEU youth from an NIH supported PHACS sub study. Epigenetics
data will be integrated with existing longitudinal echocardiographic data and biomarkers data for inflammation,
cardiac injury, and mitochondrial function. Aim 1 will identify epigenetic features in purified monocytes
associated with cardiac function and biomarkers in 120 HIV+ adolescents and young adults and 80 age/gender
matched HEU participants of the Pediatric HIV/AIDS Cohort Study (PHACS). Aim 2 will evaluate whether
changes in longitudinal echocardiographic measures over three years relate to differences in monocyte DNA
methylation patterns. The study approach will both define the immune cell-type specific epigenomes of 120
HIV+ adolescents and young adults and 80 age/gender matched HEU adolescents and young adults and
determine how longitudinal exposure to HIV/ART throughout development reshapes the immune cell
epigenome leading to progressive cardiac dysfunction. Understanding the impacts of HIV/ART on subclinical
cardiac abnormalities in adolescents and young adults living with HIV through the lens of epigenetics will be
critical to identifying novel biomarkers of subclinical cardiac abnormalities and for informing public health policy
and the design of future intervention t...

## Key facts

- **NIH application ID:** 10483606
- **Project number:** 1R21AI170252-01
- **Recipient organization:** WEILL MEDICAL COLL OF CORNELL UNIV
- **Principal Investigator:** Michael Jay Corley
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $285,826
- **Award type:** 1
- **Project period:** 2022-02-11 → 2024-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10483606

## Citation

> US National Institutes of Health, RePORTER application 10483606, Epigenetic dysregulation of inflammation linked to longitudinal cardiac toxicity in perinatal HIV infection (1R21AI170252-01). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10483606. Licensed CC0.

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