# TLR Immunotherapy to Eradicate Anatomic SIV Reservoirs

> **NIH NIH R01** · BETH ISRAEL DEACONESS MEDICAL CENTER · 2020 · $479,653

## Abstract

ABSTRACT
The eradication of Human Immunodeficiency Virus (HIV-1) from infected individuals is the ultimate goal of
antiretroviral therapy (ART). Major advances have been made towards this end with the advent of ART
regimens. Despite the sustained suppression of plasma viremia below detectable limits in infected patients for
2 or more years on ART regimens, replication competent virus can still be recovered from a variety of
subterfuges within the host, most notably long-lived quiescent memory CD4+ T lymphocytes. These and other
unknown viral reservoirs represent the final impediment to the eradication of HIV infection.
Although ART remains the gold standard of care, even intensified regimens do not impact the viral reservoir.
Therefore, alternative therapeutic strategies must be explored. The use of “shock and kill” regimens might be a
significant approach to perturb the HIV reservoir and enhance viral clearance or control. However, there are
significant gaps in our understanding of these combinatorial modalities that cannot be easily ascertained by the
study of human patients. Using our rhesus monkey (RM) model of SIV persistence (Whitney et al. Nature
2014), we propose to continue to evaluate a TLR7 agonist that we have discovered can potently reactivate SIV
and HIV-1 from latency. This new class of viral latency reversing agent is orally deliverable, and in stark
contrast to HDACi, markedly potentiates antiviral immune responses. We propose to determine the
mechanisms by which TLR7 agonists can impact established anatomic reservoirs in the setting of potent ART.
To investigate these hypotheses, we propose the following Specific Aims:
1. Determine the impact of early ART and LRAs (TLR7) upon the SIV reservoir in anatomic tissues.
2. Determine the impact of TLR7 treatment upon the constitution of the SIV reservoir in T cell and
monocyte/macrophage lineages.
3. Determine the immunologic correlates of TLR7 induced immune control on the SIV reservoir after
cessation of ART in Mamu A*01/A*02 monkeys.

## Key facts

- **NIH application ID:** 9963100
- **Project number:** 5R01AI127089-05
- **Recipient organization:** BETH ISRAEL DEACONESS MEDICAL CENTER
- **Principal Investigator:** James Burton Whitney
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $479,653
- **Award type:** 5
- **Project period:** 2016-07-01 → 2021-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9963100

## Citation

> US National Institutes of Health, RePORTER application 9963100, TLR Immunotherapy to Eradicate Anatomic SIV Reservoirs (5R01AI127089-05). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/9963100. Licensed CC0.

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