# HIV Persistence and Renewal in the Gastrointestinal, Genitourinary and Adipose Tissues

> **NIH NIH R01** · UNIVERSITY OF CALIFORNIA, SAN DIEGO · 2022 · $786,123

## Abstract

SUMMARY
HIV assaults deep tissues including the gastrointestinal (GI) and genitourinary (GU) tract within days after
transmission to a new person. It then quickly and irreversibly changes the local immune environment and
establishes a reservoir in resident cells. Our current understanding of the different mechanisms that allow HIV
persistence in GI, GU, and adipose tissues and of how the local immune environment impacts HIV reservoir
persistence and dynamics remains superficial, however. The rationale for this project is that understanding these
processes will be important for HIV cure efforts, which have until recently largely ignored non-blood reservoirs,
and to improve the health of persons with HIV (PWH) as they age.
In response to RFA DK-20-023, we built a team led by Drs. Smith and Rivera-Nieves (Co-PIs with complementary
expertise in virology, gastroenterology and mucosal immunology) with the objective to precisely define the
contributions of various viral and host mechanisms of HIV reservoir renewal and persistence across NIDDK
targeted tissues and blood, using the novel Last Gift rapid autopsy cohort.
Our overall hypothesis is that HIV reservoirs persist in NIDDK targeted tissues and are differentially renewed by
various cellular and viral mechanisms.
To address these open questions, our study will collect and analyze NIDDK targeted tissues throughout the
human GI and GU tracts and intra-abdominal and subcutaneous adipose tissue of altruistic PWH enrolled in the
Last Gift cohort, an ongoing rapid autopsy study. Immune cells collected from these individuals before death will
also be analyzed, in parallel, in order to facilitate comparison with prior work. Some participants (n=15) will
remain virally suppressed until the time of death, while others (n=5) will choose to stop their antiretroviral (ARV)
treatment before death.
The proposed research is innovative because we propose to map HIV burden and activity in tissues with different
immune and ARV environments (Aim 1), to determine the role of clonal expansion as a driver of HIV persistence
during treatment and viral rebound after treatment interruption (Aim 2) and to develop an integrative/innovative
phylogeographic Bayesian approach to jointly analyze virological and immunological data to unravel viral
dispersal and reseeding across the body in relation to local environments. By analyzing these connections, we
expect to reveal pathways and interactions that may differentially impact HIV associated inflammation.
We believe our proposed study to be significant because this is a unique opportunity to provide new insights into
the mechanisms of HIV persistence. Such findings would be important for the development of strategies aimed
to thwart local HIV-associated inflammation, which is associated with HIV pathogenesis in the gut, genital tract
and adipose tissues.

## Key facts

- **NIH application ID:** 10488262
- **Project number:** 5R01DK131532-02
- **Recipient organization:** UNIVERSITY OF CALIFORNIA, SAN DIEGO
- **Principal Investigator:** Jesus Rivera-Nieves
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $786,123
- **Award type:** 5
- **Project period:** 2021-09-17 → 2026-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10488262

## Citation

> US National Institutes of Health, RePORTER application 10488262, HIV Persistence and Renewal in the Gastrointestinal, Genitourinary and Adipose Tissues (5R01DK131532-02). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10488262. Licensed CC0.

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