# Investigating Cellular Immunometabolic Mechanisms Underlying HIV-Related Cardiovascular Disease Risk

> **NIH NIH R01** · WEILL MEDICAL COLL OF CORNELL UNIV · 2021 · $610,117

## Abstract

Older people living with HIV (PLWH) disparately experience an increased risk of cardiovascular 
disease (CVD) and develop exacerbated age-related cardiometabolic comorbidities compared to 
uninfected individuals. Multiple risk factors in older people living with HIV including 
aging, HIV alone, antiretroviral therapy, microbial translocation, traditional CVD risk 
factors, lifestyle, opportunistic infections, and substance abuse create the "perfect storm" for 
increased immune activation, systemic inflammation, atherosclerosis, and CVD. Indeed, 
studies suggest the features driving an elevated risk of CVD include both HIV-specific, and 
traditional and non- traditional CVD risk factors. Yet, therapeutically targetable biological 
mechanisms driving an exacerbated HIV- related CVD burden remain unclear. Our previous work 
identified immunometabolism dysfunction as a mechanism linked to age-related comorbidities in 
PLWH. Targetable immunometabolic features and immune cell types differentially dysregulated in 
older PLWH linked to increased CVD risk remain undefined. With a multidisciplinary team 
including expertise in immunometabolism, cardiology, radiology, and infectious disease, we are 
uniquely positioned to uncover immunometabolic changes as a key mechanism linking HIV-mediated 
immune activation and inflammation to CVD comorbidity burden. We will leverage an established 
cohort of older PLWH at WCM and enroll 100 HIV+ participants (age > 50 years) all on suppressive 
ART with undetectable plasma HIV RNA in a longitudinal study with three study visits to assess 
inter- and intraindividual variability in immunometabolic study measures. We will apply a 
state-of-the-art single cell immunometabolism assay of fresh immune cells obtained from 
participants in real-time at three time points to overcome artifacts of 
cryopreservation, profile validated inflammation and cardiac injury biomarkers, and 
acquire longitudinal advanced cardiovascular and vascular bed CT imaging at baseline and a 36 
month follow up time point. Our central hypothesis is that the synergistic effects of HIV and long 
term ART on CVD comorbidity burden is driven by an exacerbated metabolic reprogramming of monocytes 
and T cells towards glycolysis in older PLWH on ART. The specific aims are Aim 1: To longitudinally 
assess the immunometabolic state of monocytes and T cells at single cell resolution, peripheral 
inflammation, and cardiac injury markers in 100 PLWH > 50 years on stable ART. Aim 2: To quantify 
the change over time in the degree of subclinical plaque burden across the vasculature in 100 
PLWH > 50 years on stable ART and evaluate associations with immunometabolic states of 
monocyte and T cell subpopulations. The results of this longitudinal study will enhance our 
understanding of inter- and intraindividual immunometabolism dysfunction in older PLWH linked to 
subclinical atherosclerosis, provide a roadmap for early detection of CVD based on the individual 
le...

## Key facts

- **NIH application ID:** 10326950
- **Project number:** 1R01HL160392-01
- **Recipient organization:** WEILL MEDICAL COLL OF CORNELL UNIV
- **Principal Investigator:** Michael Jay Corley
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $610,117
- **Award type:** 1
- **Project period:** 2021-09-20 → 2025-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10326950

## Citation

> US National Institutes of Health, RePORTER application 10326950, Investigating Cellular Immunometabolic Mechanisms Underlying HIV-Related Cardiovascular Disease Risk (1R01HL160392-01). Retrieved via AI Analytics 2026-06-10 from https://api.ai-analytics.org/grant/nih/10326950. Licensed CC0.

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