# Formation of the HIV-1 Latent Reservoir

> **NIH NIH R01** · UNIV OF NORTH CAROLINA CHAPEL HILL · 2020 · $659,300

## Abstract

PROJECT ABSTRACT
The nature of the HIV-1 latent reservoir has recently been redefined. Our recent work has shown that a large
majority of the reservoir (on average 70%) is formed near, and presumably at, the time of therapy initiation. This
is a very different view of the reservoir from the historical one where the reservoir starts to be formed early after
infection and forms continuously. Suppression of viral replication changes the host environment to allow certain
cells, some of which are infected, to become long lived. We have also shown this is true for viral DNA even
though most of it is defective. Thus, the latent reservoir is marking a set of cells that transition to a long-lived
state with the initiation of therapy irrespective of their infection status. This new view of the latent reservoir begs
a number of key questions that are addressed in this application. First, if the reservoir is defined in a different
way does its formation have the same history? We will address this question by looking at two alternative
definitions of the latent reservoir: rebound virus during therapy discontinuation, and a putative "deep" reservoir
in both gut and lymph node tissue. Second, since our initial observations were made in a cohort of women, we
will ask the same question about the timing of reservoir formation in men. Third, since the initiation of therapy
determines when a majority of the reservoir is formed, we will examine whether the reservoir is disrupted and
reforms over a period of a drug holiday followed by therapy re-initiation. Fourth, we will determine the
differentiation state of the T cells harboring the subset of the reservoir that forms early prior to the initiation of
therapy. Fifth, we will follow the differentiation state of cells harboring the viruses that will form the long-lived
reservoir as therapy suppresses viral replication. Collectively these studies will complete our understanding of
when the reservoir forms, regardless of how one defines the reservoir, in both men and women. They will also
show the stability of the reservoir after reintroducing an inflammatory state that had previously largely prevented
the formation of the reservoir. Finally, they will start to explore the differentiation state of the T cells that form the
early reservoir and the cytokine environment present in the face of viral replication, then the differentiation state
these T cells transition to as part of the long-lived reservoir during suppressive therapy. These studies will provide
a conceptual framework for future new strategies to limit reservoir formation at the time of therapy initiation.

## Key facts

- **NIH application ID:** 10013718
- **Project number:** 1R01AI147849-01A1
- **Recipient organization:** UNIV OF NORTH CAROLINA CHAPEL HILL
- **Principal Investigator:** Ronald I Swanstrom
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $659,300
- **Award type:** 1
- **Project period:** 2020-02-13 → 2025-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10013718

## Citation

> US National Institutes of Health, RePORTER application 10013718, Formation of the HIV-1 Latent Reservoir (1R01AI147849-01A1). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10013718. Licensed CC0.

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