# Cytomegalovirus (CMV), the gut barrier and immune dysfunction in HIV

> **NIH NIH R01** · UNIVERSITY OF CALIFORNIA AT DAVIS · 2022 · $764,059

## Abstract

ABSTRACT. This REVISED collaborative R01 application addresses the impact of cytomegalovirus (CMV) on
the gastrointestinal mucosa in chronic HIV infection. We hypothesize that CMV infection contributes to the
intestinal barrier dysfunction and consequent immune activation that persist in chronic HIV infection despite
suppressive antiretroviral therapy (ART). In Aim 1, based on strong preliminary studies, we hypothesize that
CMV persistence in the gastrointestinal tract results in part from the failure of CMV-specific CD8+ T-cells to
localize to this tissue. To determine the breadth and functionality of CMV-specific T-cell responses in gut, we will
measure responses in colorectal tissue from participants in the SCOPE cohort at UCSF. To determine the effects
of CMV infection on antigen presentation in gut, we will employ the rhesus macaque model of CMV (RhCMV)
and SIVmac to study interactions between mucosal dendritic cells (DC) and T-cells ex vivo. In Aim 2, we will
leverage an externally-funded clinical trial (AIDS Clinical Trials Group Study #A5383) to directly test the
hypothesis that asymptomatic CMV replication contributes significantly to microbial translocation in treated HIV
disease. We will determine the effects of suppression of CMV replication with letermovir on systemic biomarkers
of microbial translocation as well as immune activation and gut barrier integrity assessed directly in gut mucosal
tissues. Taken together, these studies will determine the contributions of CMV to immune activation in HIV
disease, and the mechanistic bases for these effects. Aim 3 leverages a second ACTG study (#A5355) to
determine whether a modified vaccine Ankara (MVA)-based CMV vaccine can increase systemic and/or gut-
homing and mucosal CMV-specific T-cell responses in treated HIV infection. Failure of a therapeutic anti-CMV
vaccine to elicit gut-homing CMV-specific T-cell responses and to reduce mucosal CMV shedding may
compromise its ability to reduce systemic immune activation in treated HIV infection and would highlight the need
for optimization of vaccination strategies to improve mucosal responses. (Note: Aims 2 and 3 do not meet the
NIH definition of a clinical trial; the ancillary studies in these Aims only add additional measures to pre-existing
trials).

## Key facts

- **NIH application ID:** 10372191
- **Project number:** 5R01AI155680-02
- **Recipient organization:** UNIVERSITY OF CALIFORNIA AT DAVIS
- **Principal Investigator:** PETER W HUNT
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $764,059
- **Award type:** 5
- **Project period:** 2021-03-15 → 2026-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10372191

## Citation

> US National Institutes of Health, RePORTER application 10372191, Cytomegalovirus (CMV), the gut barrier and immune dysfunction in HIV (5R01AI155680-02). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10372191. Licensed CC0.

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