# Defining HIV reservoirs that rebound following suspension of ART

> **NIH NIH R01** · SEATTLE CHILDREN'S HOSPITAL · 2020 · $785,807

## Abstract

ABSTRACT
In the twenty years since effective HIV treatments became available, the lifespan of HIV-infected adults in high-
resource settings has increased to within a decade of uninfected individuals. Nevertheless, antiretroviral
treatments (ART) fall short in restoring health, and if therapy is discontinued virus usually rebounds to
pretreatment levels due the persistence and reactivation of proviruses. Curative therapies are being sought,
including therapeutic vaccines, chemotherapies paired with stem-cell transplant, chimeric antigen receptor T
cells, neutralizing and immune modulating antibodies, gene therapies, cytokines and initiation of ART during
acute infection. While some of these approaches have reduced the “reservoirs” of infectious viruses and in one
case may have cured HIV infection, a better understanding of the mechanisms underlying HIV persistence is
needed to develop an effective, safe and economical cure. HIV reservoirs are primarily established early in
infection, and while they decay and change in composition during ART, the mechanisms that sustain reservoirs
are only partially known. We hypothesize that HIV reservoirs are maintained by: (1) Integrated proviruses that
modulate gene expression to promote survival of these cells, allowing infected cells to persist by proliferation
or latency; (2) HIV-specific immune responses become exhausted due to dysregulation of T-regulatory cells
resulting from provirus integration; and (3) Epigenetic marks repress expression of proviral DNA, allowing
infected cells to persist due to “deep” latency of proviruses. We propose studies to explore the role of these
mechanisms in sustaining HIV reservoirs using specimens collected prospectively from a unique Belgian
cohort of chronically infected individuals sampled during ART-suppression as well as during and after an
analytical treatment interruption (ATI). Samples for this study include blood, cerebral spinal fluid, bone marrow,
bronchioalveolar lavage fluid, lymph node, duodenum, ileum, and colon. The knowledge gained from the
proposed studies should point to interventional strategies that could be tested and potentially contribute to the
goal of developing an intervention to cure HIV infection.

## Key facts

- **NIH application ID:** 9976441
- **Project number:** 5R01AI134419-04
- **Recipient organization:** SEATTLE CHILDREN'S HOSPITAL
- **Principal Investigator:** Lisa M Frenkel
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $785,807
- **Award type:** 5
- **Project period:** 2017-08-17 → 2022-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9976441

## Citation

> US National Institutes of Health, RePORTER application 9976441, Defining HIV reservoirs that rebound following suspension of ART (5R01AI134419-04). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9976441. Licensed CC0.

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