# High-Definition Characterization of the Persistence and Perturbation of the HIV Reservoir

> **NIH NIH P01** · BRIGHAM AND WOMEN'S HOSPITAL · 2022 · $1,739,430

## Abstract

SUMMARY
Strategies for achieving sustained HIV remission must target the long-lived reservoir of HIV-infected cells.
These reservoirs remain a challenge to study because they make up a very small fraction of immune cells, can
be located in difficult to sample anatomic sites (e.g., the central nervous system [CNS]), and are generally less
well studied in individuals who undergo treatment interruption. Here we aim at answering three critical
questions: (A) what are the drivers of clonal expansion, activation of HIV-1-infected cells, and viral rebound
timing – is it viral factors (such as HIV-1 integration site) that provide survival benefit of the infected cells, or is
it host factors (such as immune responses to antigen or HIV stimulation) that drive the proliferation of HIV-1-
infected cells and viral rebound after treatment interruption (Project 1)? (B) How do HIV-1-infected cells persist
and distribute between peripheral blood and the anatomical sanctuary of the CNS (Project 2)? (C) Do HIV-1
eradication strategies, such as broadly neutralizing antibodies (bnAbs), reprogram host immune effector
responses, transcriptionally, epigenetically, and functionally (Project 3)? Overall, we aim at understanding the
expansion dynamics, tissue distribution, and rebound predictors of HIV-1 persistence using several unique
clinical cohorts and innovative methods to provide critical insight to mechanisms of HIV-1 persistence and
strategies for HIV-1 eradication. We will use these samples to define the mechanisms that govern spontaneous
HIV-1 reactivation during treatment interruption and the persistence of viremia despite effective antiretroviral
therapy (ART), specifically exploring virus and immune mechanisms that may impact viral maintenance and
rebound (Project 1). We focus on the establishment, persistence, clonal proliferation, and rebound competence
in different stages of infection of HIV-1 brain reservoirs, a critically important virus sanctuary that has been a
challenge to study in detail (Project 2). Lastly, we explore the immune mechanisms that impact virus reservoir
dynamics and the role of host epigenetics and immune cell function in the control and pruning of the HIV-1
proviral landscape in the context of a first-in-human broadly neutralizing antibody (Project 3). These Projects
will be supported by an Administrative Core and a Data Analytics & Modeling Core.
1

## Key facts

- **NIH application ID:** 10469108
- **Project number:** 1P01AI169768-01
- **Recipient organization:** BRIGHAM AND WOMEN'S HOSPITAL
- **Principal Investigator:** Ya-Chi Ho
- **Activity code:** P01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $1,739,430
- **Award type:** 1
- **Project period:** 2022-07-01 → 2027-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10469108

## Citation

> US National Institutes of Health, RePORTER application 10469108, High-Definition Characterization of the Persistence and Perturbation of the HIV Reservoir (1P01AI169768-01). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10469108. Licensed CC0.

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