# Harnessing IL-10 in cART treated SIV infected macaques to restore immunity and to eradicate HIV

> **NIH NIH R37** · EMORY UNIVERSITY · 2023 · $793,338

## Abstract

While current ART has prevented AIDS and reduced HIV-related morbidities and mortality for the majority
of infected individuals, a therapeutic regimen able to eradicate or functionally cure HIV infection does not
exist. Persistence of HIV in a small pool of latently infected cells remains the major obstacle for HIV
eradication largely because the mechanisms that underlie viral persistence are still unknown. Our group
has generated significant and convincing results in cART treated HIV infected humans and SIV infected
rhesus macaques (RMs) suggesting that Interleukin(IL)-10 plays an important role in the establishment and
maintenance of the HIV reservoir by (i) impeding the early antiviral innate and the HIV/SIV specific adaptive
immune response and (ii) promoting the differentiation of Tfh and Tr1 cells that are major HIV/SIV
reservoirs. The importance of IL-10 in the establishment and maintenance of HIV has prompted Merck to
successfully develop a Rhesus form of an anti-human IL-10 Ab that is currently being tested in clinic;
administration of this Ab in a proof of concept study to SIV infected RMs was safe and well tolerated; it also
recapitulated several of the biological activities of the human Ab as it showed a negative impact on Tfh
frequencies which could translate in a smaller reservoir. In this proposal, we will test the hypothesis that
neutralization of IL-10 activity systemically and in lymphoid tissues will lead to restoration of cellular
immune responses, decreased Tfh and Tr1 numbers, and a decay in HIV reservoir. Biomarkers that predict
successful clinical interventions involving anti-IL-10 and leading to HIV eradication are not available. In Aim
1, we will perform an unbiased OMICs integrated approach to identify cell subsets, soluble effector
molecules, metabolites and molecular pathways, which underlie the modulation of HIV reservoirs by IL-10
in cell subsets isolated from PBMCs and tissues from cART treated HIV infected subjects. We will identify
markers that are associated to low levels of IL-10 and conversely to lower HIV reservoir in Tfh and Tr1 cells
and efficient innate antiviral and cell mediated immunity. These markers will be used to monitor the impact
of the anti-IL-10 intervention that aims at restoring innate antiviral immunity and cell mediated immunity for
HIV eradication. Direct demonstration that IL-10 regulates HIV persistence will be provided by examining
the impact of IL-10 blockade on virus persistence in a large study of ART-treated, SIV-infected RMs.
Preclinical trial of Aim 2 will allow us to determine the restoration of innate immunity by early IL-10 blockade
as this intervention should inhibit the upregulation of NLRX-1, a molecule we have shown to play a critical
role in the early HIV/SIV dissemination and conversely in the seeding of the HIV/SIV reservoir. Pre-clinical
trial of Aim 3 should allow the restoration of the adaptive immune response by preventing the development
of IL-10 producing Tr1 cells;...

## Key facts

- **NIH application ID:** 10588314
- **Project number:** 4R37AI141258-07
- **Recipient organization:** EMORY UNIVERSITY
- **Principal Investigator:** Rafick Pierre Sekaly
- **Activity code:** R37 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2023
- **Award amount:** $793,338
- **Award type:** 4C
- **Project period:** 2023-07-01 → 2028-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10588314

## Citation

> US National Institutes of Health, RePORTER application 10588314, Harnessing IL-10 in cART treated SIV infected macaques to restore immunity and to eradicate HIV (4R37AI141258-07). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10588314. Licensed CC0.

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