# Project !: Differential contribution of resting CD4+ T cells and resident macrophages to viral rebound after antiretroviral treatment interruption

> **NIH NIH P01** · JOHNS HOPKINS UNIVERSITY · 2021 · $354,086

## Abstract

Time between antiretroviral treatment interruption (ART-i) and the detection of viremia in plasma
is a direct reflection of the size of the functional reservoir. Despite controversies about residual
viremia, the persistence of active but limited HIV-1 and SIV replication during antiretroviral therapy
(ART), data from reports where patients experienced viral rebound after months without ART
corroborate the hypothesis that the latent reservoirs are composed of only latent or non-replicating
forms of virus. Therefore, reducing the size of the replication competent functional reservoirs
would delay or prevent viral rebound. In this project we will characterize and quantitate the latent
SIV reservoir in blood and tissues during ART suppression and during successive steps after
stopping ART (before detectable plasma viral load (pVL), ascending pVL, and set point post
rebound). Quantitation of cells harboring replication competent SIV genomes will define the
cellular reservoirs and identify the anatomic locations where these reservoirs are located.
Performing these experiments during the early stage of ART-i will determine the contribution of
each reservoir to viral rebound. These studies will also identify the distinct reactivating properties
of resting memory CD4+ T cells (rmCD4s) and the three different macrophages (MØ) subsets:
monocytes (which are not a MØ per se, but the blood precursors of a portion of tissue MØ);
monocyte-derived MØ in tissues; and resident, or fetal tissue-derived MØ. In addition to using
immunohistochemistry (IHC) and in situ hybridization (ISH) to characterize the virus-producing
cells in tissue sections during viral rebound, we will analyze the functional reservoir ex vivo
comparing five different techniques (discussed below).
We hypothesize that: 1) Both rmCD4s and tissue MØ are latently infected in vivo and form the
functional viral reservoir that can be reactivated when ART is interrupted. 2) Rebound viruses can
originate from multiple cell types and tissues. 3) Results from the assays here proposed will
predict the kinetics of viral rebound post ART-i. 4) In vivo CD4+ T cell depletion will decrease the
latent CD4+ reservoir and delay rebound after ART-i.

## Key facts

- **NIH application ID:** 10174708
- **Project number:** 5P01AI131306-05
- **Recipient organization:** JOHNS HOPKINS UNIVERSITY
- **Principal Investigator:** Lucio Gama
- **Activity code:** P01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $354,086
- **Award type:** 5
- **Project period:** 2017-06-23 → 2024-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10174708

## Citation

> US National Institutes of Health, RePORTER application 10174708, Project !: Differential contribution of resting CD4+ T cells and resident macrophages to viral rebound after antiretroviral treatment interruption (5P01AI131306-05). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10174708. Licensed CC0.

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