# Reservoir activity and recrudescent virus composition in HIV and SIV rebound

> **NIH NIH P01** · UNIVERSITY OF CALIFORNIA AT DAVIS · 2020 · $298,863

## Abstract

As the HIV/AIDS research field embarks on an endeavor to cure HIV-1 infection, insight into the reservoirs that
sustain viral persistence in the face of suppressive antiretroviral therapy (ART) is essential. Most of the focus
has been on characterization of proviruses and viral outgrowth assays (VOA) using circulating CD4+ T-cells
that may have limited ability to inform on the nature of the reservoirs in tissues and more importantly, the origin
of the viruses that recrudesce upon ART interruption. Furthermore, these approaches do not reveal the
potential contribution of non-CD4+ T-cells, such as tissue macrophages, to viral persistence and rebound.
The timing and composition of rebounding viremia is likely to reflect the nature of the reservoir from which it
originated and the quality of host antiviral immunity levied against it. Project 3 will assess viral reservoir
activity prior to treatment interruption, as well as the composition of rebounding viremia, to gain
insight into the virologic mechanisms whereby host antiviral immunity impacts viral rebound activity.
Project 1 will provide longitudinal samples from completed and planned human therapeutic vaccine trials (BCN
ATI, RISVAC03, BCN02 and AELIX003). The SIV macaque model (Project 2) will provide longitudinally
sampled blood and tissues from ART-suppressed, RhCMVd10/SIV-vaccinated macaques after treatment
interruption. Crucially, both projects allow the earliest sampling of rebounding viremia, which is most likely to
reflect its origins in the reservoirs that persist under ART suppression.
We hypothesize that immune responses in macaques elicited by RhCMVd10/SIV vaccination and in humans
by a viral load “data-informed” vaccine, impact viral reservoir activity and that this is manifest by an impact on
time to viral rebound as well as activity and composition of the viral reservoir. To pursue this hypothesis, we
propose the following specific aims:
The objectives are to (i) evaluate the effect of therapeutic vaccination on viral reservoir activity, (ii) assess the
effect of therapeutic vaccination on rebounding virus composition, and (iii) determine whether macrophage-
tropic viruses present in rebounding viremia have a macrophage origin.

## Key facts

- **NIH application ID:** 9963123
- **Project number:** 5P01AI131568-04
- **Recipient organization:** UNIVERSITY OF CALIFORNIA AT DAVIS
- **Principal Investigator:** Mario Stevenson
- **Activity code:** P01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $298,863
- **Award type:** 5
- **Project period:** 2017-07-19 → 2022-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9963123

## Citation

> US National Institutes of Health, RePORTER application 9963123, Reservoir activity and recrudescent virus composition in HIV and SIV rebound (5P01AI131568-04). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/9963123. Licensed CC0.

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