# The impact of proviral epigenetics on HIV-1 rebound

> **NIH NIH R21** · UNIVERSITY OF CALIFORNIA, SAN DIEGO · 2022 · $197,500

## Abstract

Abstract
Despite the successful development of antiretroviral therapies (ART), the long-awaited cure for HIV has still not
been discovered. The virus integrates into DNA of tissues throughout the body and becomes latent after
institution of ART. Persons receiving ART cannot discontinue their medications, as in most cases the virus will
simply rebound upon ART cessation. One approach to finding a cure is to eliminate the reservoir by bringing
the virus out of latency so that infected cells might be killed by ART or the host immune system. Epigenetic
mechanisms are believed to play an important role in retroviral persistence and latency, yet little is known
about the epigenetic markers associated with the HIV reservoir. Recent studies have found a role for
repressive histone methylation in the epigenetic control of HIV latency in primary cells expanded in vitro, but
there are no studies in clinical samples without in vitro manipulation. The objective of this proposal is to
establish patterns of two repressive epigenetic modifications associated with HIV proviruses and their
surrounding integration sites in peripheral blood, and to determine how the presence of these modifications
affects chromatin accessibility of the HIV provirus and its subsequent impact on viral rebound following ART
interruption. Using longitudinal peripheral blood samples from seven ART Treatment Interruption (ATI) cohorts
from the AIDS Clinical Trials Group, we will examine cytosine methylation, H3K27me3, and open chromatin
across each provirus and its surrounding integration sites from people with HIV pre- and post- ATI. Using these
data, we will examine the combinatorial effects of repressive epigenetic marks upon chromatin accessibility of
the provirus and its surrounding genomic environment, and then further evaluate how these epigenetic marks
impact rebound post-ATI. The results of the proposed studies will provide crucial information about the
epigenetic regulation of HIV suppression during ART and its effect upon viral rebound during ATI. This will
yield putative targets to eliminate HIV from the reservoir.

## Key facts

- **NIH application ID:** 10375596
- **Project number:** 5R21AI162225-02
- **Recipient organization:** UNIVERSITY OF CALIFORNIA, SAN DIEGO
- **Principal Investigator:** Sarah Adrianne LaMere
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $197,500
- **Award type:** 5
- **Project period:** 2021-03-19 → 2024-02-29

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10375596

## Citation

> US National Institutes of Health, RePORTER application 10375596, The impact of proviral epigenetics on HIV-1 rebound (5R21AI162225-02). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10375596. Licensed CC0.

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