# The enteric microbiome in HIV-associated chronic immune activation and cardiovascular disease

> **NIH NIH R01** · MASSACHUSETTS GENERAL HOSPITAL · 2020 · $507,964

## Abstract

Project Summary
Despite the success of antiretroviral therapy (ART), individuals infected with Human Immunodeficiency Virus
(HIV) still have a greater mortality than those who are uninfected, mostly due to death from inflammation-
related non-communicable diseases (NCDs), such as cardiovascular disease (CVD) and kidney dysfunction.
The drivers of this chronic immune activation and associated CVD remain largely unknown. Recent studies
have shown that HIV infection results in disruptions in the gut microbial community and these alterations are
associated with gut barrier dysfunction, bacterial translocation, and systemic immune activation. However,
published studies have primarily examined populations in the developed world, even though the greatest
burden of HIV-infection and associated CVD exists in the developing world. We remain the only group to report
on HIV-associated changes in the gut microbiome in populations living in sub-Saharan Africa. Our published
studies and preliminary data indicate that there are clear shifts in the gut microbiome, both bacterial and viral,
with HIV-infection and that these correspond to increased measures of systemic inflammation. Independent of
HIV, changes in the gut microbial community have been shown to produce inflammatory metabolites that
cause macrophage and platelet activation, thrombosis, and arterial plaque formation. We propose to study
HIV-associated gut microbial changes in two sub-Saharan African populations and measure systemic immune
activation and cardiovascular outcomes associated with these changes. These studies will identify microbial
candidates that we will then use in in vitro and in vivo models to investigate the causative relationship between
HIV-associated gut microbial community changes and CVD. We will expose gut and vascular cells to HIV-
associated microbes of interest and measure the inflammatory response to these organisms. We will also use
an established murine model of atherosclerosis to transplant candidate microbes and/or stool communities into
animals to characterize the development of CVD induced by these microbes. The specific aims of this project
are to: 1) Determine the associations between changes in enteric microbial communities, increased immune
activation, and cardiovascular disease in HIV-infected individuals in sub-Saharan Africa and 2)
Utilize both in
vitro and in vivo models to assess mechanisms by which HIV-associated enteric microbial communities
promote chronic inflammation and cardiovascular disease.
The goal of the proposed work is to identify specific
mechanisms by which HIV-associated alterations in the gut microbiome (including bacteria, viruses, fungi and
parasites) contribute to CVD pathogenesis in chronic HIV infection and help inform the development of new
therapeutic interventions that leverage the gut microbiome to extend lifespan and improve quality of life for
HIV-infected individuals.

## Key facts

- **NIH application ID:** 9933989
- **Project number:** 5R01HL138646-04
- **Recipient organization:** MASSACHUSETTS GENERAL HOSPITAL
- **Principal Investigator:** Scott A. Handley
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $507,964
- **Award type:** 5
- **Project period:** 2017-09-01 → 2022-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9933989

## Citation

> US National Institutes of Health, RePORTER application 9933989, The enteric microbiome in HIV-associated chronic immune activation and cardiovascular disease (5R01HL138646-04). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/9933989. Licensed CC0.

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