# Immunological Strategies to Modulate SIV Rebound Following ART Interruption

> **NIH NIH P01** · UNIVERSITY OF PENNSYLVANIA · 2021 · $1,497,359

## Abstract

Abstract. The majority of antiretroviral (ART) treated HIV-infected individuals experience detectable rebound
in HIV plasma viremia within weeks following interruption of ART. The kinetics of rebound virus reactivation are
a correlate of the size of the archived reservoir and a key measure of reductions therein. Recent mathematical
estimates suggest that virus reactivation events occur every 5-8 days following ART removal. Immunologic
strategies to prevent or extend the time to virus reactivation and HIV rebound are critically needed to enable
durable control or eradication of HIV within infected individuals. Rebounding plasma virus following ART
interruption is thought to primarily originate from long-lived resting CD4+ T cell reservoirs, largely PD-1+ T
follicular helper cells, within secondary lymphoid tissue (LT) such as lymph nodes, spleen, tonsil, bone marrow,
and lymphoid aggregates within gut tissue. This P01 proposal will explore and model two immunologic
strategies to prevent, limit, or delay viral rebound by (1) directly targeting rebounding virus through passive nAb
therapy in transmitted founder-SHIV infected rhesus macaques (K. Bar/G. Shaw, Project 1) and (2) inhibiting
lymphocyte egress from LT to both prevent infected CD4+ T cell redistribution and enable the interaction
between reactivated infected CD4+ T cells and protective CD8+ T cells in lymphoid tissue after ART
interruption in SIV infected rhesus macaques (M. Betts, Project 2). Importantly, we will employ bar-coded SIV
and SHIV viruses in both projects (B. Keele), allowing us to precisely track reactivation rate at a clonal level,
and to discern potential tissue and cell types of viral reactivation. These projects will be supported by experts in
mathematical modeling (M. Davenport, Analysis and Modeling Core) and nonhuman primate studies (M.
Paiardini/G. Silvestri Non-Human Primate Core). Together these studies will provide novel insights into
immunological strategies to delay or prevent viral rebound after ART interruption.
PHS 398/2590 (Rev. 06/09) Page Continuation Format Page

## Key facts

- **NIH application ID:** 10224003
- **Project number:** 5P01AI131338-05
- **Recipient organization:** UNIVERSITY OF PENNSYLVANIA
- **Principal Investigator:** Katharine June Bar
- **Activity code:** P01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $1,497,359
- **Award type:** 5
- **Project period:** 2017-08-01 → 2024-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10224003

## Citation

> US National Institutes of Health, RePORTER application 10224003, Immunological Strategies to Modulate SIV Rebound Following ART Interruption (5P01AI131338-05). Retrieved via AI Analytics 2026-06-01 from https://api.ai-analytics.org/grant/nih/10224003. Licensed CC0.

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