# Integrated analysis of CVD risk in HIV: gut microbiota, immune function and metabolites

> **NIH NIH R01** · ALBERT EINSTEIN COLLEGE OF MEDICINE · 2021 · $777,067

## Abstract

Summary/Abstract
Our prior work in HIV cohort studies provides insights into the viral, inflammation, immune activation and
antiretroviral therapy related risk factors for HIV-related CVD risk. Yet, an understanding of its pathophysiology
remains incomplete. Emerging evidence suggests that gut microbiota (GMB) altered during HIV infection
correlates with increased immune activation and disrupted metabolite profiles, but the role of GMB in HIV-
related CVD is unknown. Our preliminary data show that in HIV infection, progression of atherosclerosis is
associated with higher circulating sCD14, a marker of monocyte activation, and increased tryptophan
catabolism. This preliminary work presents two promising candidates linking GMB and CVD risk in HIV
infection which we propose to study using integrated “Omics” approaches. In addition to these hypothesis-
driven study aims, we will also generate novel hypotheses linking GMB, host immune activation and
metabolomics profiles associated with CVD risk. We will leverage the Women’s Interagency HIV Study (WIHS)
and Multicenter AIDS Cohort Study (MACS) >20 year follow-up for biospecimens, atherosclerosis and other
CVD measures, and HIV parameters. Our longitudinal semi-annual measures allow us to subset individuals
according to long-term HIV treatment, disease progression markers (CD4+ T-cell count, viral load), and
comorbidity, with inclusion of matched HIV-uninfected participants. In this project, We will extend our
established collaborations with leading labs to gather multi-dimensional data among 400 women and men (~65%
of whom are HIV+), including stool GMB metagenomics, serum and cellular inflammation and immunologic
markers (sCD14, monocyte transcriptomics), metabolomics, and measures (carotid artery ultrasound imaging
over 4 year follow-up). Findings from this intensively studied group will then be extended to a larger sample of
746 women and men with metabolomics and longitudinal atherosclerosis data. In this project, we will have the
opportunity to identify immune activation and metabolites underlying the role of GMB in CVD, which may be
specific to HIV+ individuals, or accentuated in the setting of HIV.

## Key facts

- **NIH application ID:** 10067482
- **Project number:** 5R01HL140976-05
- **Recipient organization:** ALBERT EINSTEIN COLLEGE OF MEDICINE
- **Principal Investigator:** ROB KNIGHT
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $777,067
- **Award type:** 5
- **Project period:** 2018-01-15 → 2023-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10067482

## Citation

> US National Institutes of Health, RePORTER application 10067482, Integrated analysis of CVD risk in HIV: gut microbiota, immune function and metabolites (5R01HL140976-05). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10067482. Licensed CC0.

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