# Nonhuman Primate Core

> **NIH NIH P01** · NORTHWESTERN UNIVERSITY · 2024 · $517,623

## Abstract

A major barrier to HIV cure is the persistence of HIV-1 infected cells that constitute the viral reservoir which even 
after prolonged combined antiretroviral therapy (cART), fuels a consistent and rapid rebound if viral replication 
following cART interruption. This has unfortunately been true even for patients initiated on ART during acute 
infection. Thus, long-term persistent HIV reservoirs are seeded rapidly post infection, and our team and others 
have confirmed this finding in the nonhuman primate model of HIV. In addition, data from several groups and 
ours strongly suggest that residual viral replication is actually ongoing in various lymphoid tissues in spite of 
highly active cART, be it due to poor drug penetration, drug metabolization, or sanctuaries with limited antiviral 
immune contribution. Preliminary data from our ongoing reservoir investigations in the simian immunodeficiency 
infection of rhesus macaques with ART initiated less than 7 days post infection have led to unexpected findings: 
1) we were able to see SIV expand and colonize the entire host for >1 week post cART initiation using 
immunoPET/CT monitoring, with signal decreasing thereafter; 2) Even after 6-8 months of cART, 
immunoPET/CT was sensitive enough to detect residual viral (protein) signal in tissues in spite of undetectable 
viremia in the blood; upon ART interruption, viral signals rebounded as early as 4 days post cART interruption 
(ATI) but also 2 weeks before detection of virus in plasma; analysis of the tissues and cells fueling this initial 
rebound surprisingly showed a paucity if not absence of T cells, but predominantly myeloid type cells, among 
which, many appeared positive for the mast cell specific tryptase biomarker. While our team had documented 
the ability of developing mast cells to be susceptible to HIV and SIV infection in vitro in the past, this was the first 
clear evidence that mast cells may contribute at the very least to the very early seeded SIV reservoir. In this 
application, we propose to quantify and map the reservoir formation in the context of cART initiation at 6 weeks 
post infection, as more representative of the human clinic, using a series of state of the art imaging guided 
collection techniques allowing for detailed cellular and viral analyses of the reservoirs obtained at various times 
of cART and early ATI. Next we propose to address the functional viral reservoir following prolonged cART with 
and without immune interventions designed to allow for transient viral replication, and finally, investigate the role 
of such interventions on the reservoir dynamic and composition upon ATI, in efforts to articulate novel strategies 
to silence viral reservoirs in the future

## Key facts

- **NIH application ID:** 11082754
- **Project number:** 5P01AI169600-03
- **Recipient organization:** NORTHWESTERN UNIVERSITY
- **Principal Investigator:** Francois J Villinger
- **Activity code:** P01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $517,623
- **Award type:** 5
- **Project period:** 2022-07-15 → 2027-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/11082754

## Citation

> US National Institutes of Health, RePORTER application 11082754, Nonhuman Primate Core (5P01AI169600-03). Retrieved via AI Analytics 2026-05-28 from https://api.ai-analytics.org/grant/nih/11082754. Licensed CC0.

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