# Impact of the gastrointestinal microbiome on HIV reservoirs

> **NIH NIH R01** · UNIV OF NORTH CAROLINA CHAPEL HILL · 2021 · $777,023

## Abstract

Antiretroviral therapy (ART) can reduce viremia to undetectable levels in people living with HIV (PLWH) .
However, replication-competent virus persists in peripheral blood and tissues that is capable of
reestablishing the infection upon antiretroviral therapy interruption (ATI). One of our long-term goals is to
aid the development of effective HIV cure strategies by gaining a better understanding of the host
physiological and metabolic processes by which cellular reservoirs are established and maintained, and
those of viral reactivation. Regardless of how HIV infection is acquired, the gastrointestinal (GI) tract is a
major site of HIV replication. Although the majority of immune cells in the body, including CD4+ T cells,
reside in the GI tract, little is known about the HIV reservoir that is established in this tissue. Analyses of
ART-treated patients have demonstrated higher HIV-DNA levels in GI tract cells compared to blood cells,
suggestive of a larger HIV reservoir. Examination of HIV transcripts in cells from the blood and rectum of
ART-treated PLWH also indicates that the GI tract may be enriched in latently-infected cells and suggests
that HIV latency is maintained by different mechanisms in the GI tract and/or that a deeper s tate of latency
may be maintained. Based on these observations, our overarching hypothesis is that HIV establishes a
latent infection in the GI tract that contributes to virus rebound during ATI. T o our knowledge there is
virtually no information addressing the role of the microbiome in establishing or maintaining the latent
reservoir in the GI tract. Currently, a large amount of indirect evidence suggests that the GI microbiome is
involved in HIV persistence. The GI microbiome in PLWH promotes inflammation and immune activation in
the GI tract, which may influence HIV reservoir size. Furthermore, in vitro studies show that microbiota and
microbial metabolites can influence HIV transcription. Therefore, we further hypothesize that the intestinal
microbiome contributes to the establishment and persistence of the HIV reservoir and thereby impacts the
contribution of the GI tract to virus rebound. A role for the microbiome in HIV remission would be
fundamentally important to HIV cure development. Previously, we and others demonstrated that HIV
establishes a latent infection in ART-suppressed humanized mice that upon discontinuation of ART results
in robust virus rebound. Importantly, we recently demonstrated reproducible induction of HIV in resting
CD4+ T cells in multiple tissues of ART-suppressed humanized mice using two different latency reversal
approaches. Our objective is to analyze the HIV reservoir in the GI tract using BLT humanized mice, a well-
characterized model of HIV latency, persistence and reactivation. We will 1) analyze HIV reservoir formation
in the GI tract, 2) evaluate the contribution of the GI tract to viral rebound, and 3) assess HIV induction in
the Gl tract by latency reversing agents. We wi...

## Key facts

- **NIH application ID:** 10374223
- **Project number:** 1R01DK131585-01
- **Recipient organization:** UNIV OF NORTH CAROLINA CHAPEL HILL
- **Principal Investigator:** J. Victor Garcia-Martinez
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $777,023
- **Award type:** 1
- **Project period:** 2021-09-21 → 2026-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10374223

## Citation

> US National Institutes of Health, RePORTER application 10374223, Impact of the gastrointestinal microbiome on HIV reservoirs (1R01DK131585-01). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10374223. Licensed CC0.

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