# Understanding Inflammatory and Metabolic Pathways of Myocardial and Vascular Dysfunction in South African Youth Living with Perinatal HIV

> **NIH NIH R01** · LURIE CHILDREN'S HOSPITAL OF CHICAGO · 2020 · $733,852

## Abstract

ABSTRACT
Cardiovascular disease (CVD) remains a significant concern in adults living with HIV (AHIV) on antiretroviral
therapy (ART). Little is known about subclinical or early upstream CVD pathogenesis in youth living with
perinatally acquired HIV (YPHIV) who stand to benefit the most from early identification of subclinical CVD.
ART expansion has reduced pediatric HIV mortality, allowing YPHIV to reach adulthood, but not without
lifelong exposure to immune activation, inflammation, and ART, all of which potentiate CVD. Several studies
including ours have shown subclinical myocardial dysfunction in YPHIV, but few have evaluated underlying
metabolic pathways or been conducted with well-matched comparison groups of youth living with non-
perinatally acquired HIV (YNPHIV) and HIV-unexposed uninfected (HUU) youth in sub-Saharan Africa, where
currently 90% of the world’s children with HIV reside. We have demonstrated high rates (25%) of right
ventricular systolic dysfunction and insulin resistance (21%) in our cohort of South African YPHIV. In addition,
our YPHIV have an increased risk for endothelial dysfunction and dyslipidemia compared to uninfected youth.
However, detailed sensitive imaging data to comprehensively measure myocardial and vascular dysfunction
are urgently needed in YPHIV to understand the role of these precursors in end conditions such as heart
failure and CVD which we have shown to be more prevalent in AHIV. In addition, studies in YPHIV of
underlying metabolic pathways involved in early/primordial factors across the cascade of myocardial/vascular
dysfunction resulting in CVD are lacking and critical to providing insight into early prediction and potential
mitigation of the development of cardiometabolic complications among YPHIV into adulthood. For this proposal
we will leverage the Cape Town Adolescent and Antiretroviral Cohort (CTAAC) to assess whether ART-treated
perinatally acquired HIV is associated with worsened subclinical myocardial or vascular dysfunction over time
using YNPHIV and HUU youth comparison groups of similar age, sex, and body surface area (BSA) and
employing cardiovascular magnetic resonance imaging (CMR), a sensitive multiparametric method of
investigating multiple cardiovascular domains. Next, we will use novel metabolomics techniques to explore
whether a signature cluster of intermediary or proinflammatory metabolites representing eicosanoid
imbalances and mitochondrial shifts in fatty acid oxidation are different in YPHIV compared to YNPHIV or HUU
youth and are associated with subclinical myocardial or vascular dysfunction in YPHIV. Lastly, we will explore
how inflammation correlates with these eicosanoid imbalances and mitochondrial shifts in fatty acid oxidation in
YPHIV. These results will expand our understanding of the pathogenesis and interplay between metabolic
dysregulation and subclinical myocardial dysfunction as well as elucidate key pathways of cardiac dysfunction
which may identify those YPH...

## Key facts

- **NIH application ID:** 10032160
- **Project number:** 1R01HL151287-01A1
- **Recipient organization:** LURIE CHILDREN'S HOSPITAL OF CHICAGO
- **Principal Investigator:** Jennifer Jao
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $733,852
- **Award type:** 1
- **Project period:** 2020-05-01 → 2025-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10032160

## Citation

> US National Institutes of Health, RePORTER application 10032160, Understanding Inflammatory and Metabolic Pathways of Myocardial and Vascular Dysfunction in South African Youth Living with Perinatal HIV (1R01HL151287-01A1). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10032160. Licensed CC0.

---

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