# Collaboratory of AIDS Researchers for Eradication (CARE)

> **NIH NIH UM1** · UNIV OF NORTH CAROLINA CHAPEL HILL · 2022 · $5,246,834

## Abstract

Abstract
 Since its inception in 2011, the Martin Delaney Collaboratory program has made important advances towards
a cure for HIV. In response to the Martin Delaney Collaboratories (MDC) for HIV Cure Research RFA, we seek
to continue to advance the field by discovery of successful modalities to cure HIV infection. We will expand our
expertise and work toward a better understanding of persistent HIV infection, the discovery of novel approaches
to disrupt latency, methods to clear the HIV reservoir, and identification of strategies to control viral rebound. By
building on the significant advances that we have made to develop, implement, and execute a suite of pre-clinical
experiments that represent the most advanced and novel concepts, we will continue to pursue our central
unifying hypothesis that reversing HIV latency such that viral proteins are expressed, in parallel with interventions
that speed the clearance of cells emerging from latent infection, will ultimately lead to eradication of persistent
HIV infection. In parallel to the efforts to clear the infection, we will pursue interventions to prevent rebound of
viremia after ART interruption. We will leverage a broad portfolio of tools from both academic and industry
partners, and apply new discoveries, demonstrating proof-of-concept for clinical initiatives.
 We will engage academic scientists and clinicians, industry investigators, and the community to a) define
novel targets to destabilize proviral genomes that persist despite antiretroviral therapy (ART) b) define novel
approaches to block proviral establishment c) develop and deploy novel effectors to clear viral reservoirs, d)
delineate effective strategies to prevent rebound viremia that might emanate from such reservoirs after ART is
discontinued and e) create bridges to the community to improve the understanding of and access to HIV cure
research and clinical trials. Our initial efforts will focus on biology discovery to illuminate new host targets for
latency reversal, and the validation of the novel biological concept of latency prevention. Universal strategies for
proviral control or clearance will be developed and tested, including those based on HLA-E targeting, eCD4, and
CD4 mimetics. Our major recent advance in latency reversal via NF-kB signaling will be further developed in
both non-human primate and humanize mice models, in combination with candidates to clear infected cells.
 We envision an iterative process with insights gained in ex vivo and pre-clinical studies, carried forward to
enhance the next step in clinical development and, importantly, fed back to scientists to validate assays or
hypotheses, and explore new directions. As we have done in the past, we will develop human clinical trials to
address questions and test concepts developed in our work through funding mechanisms distinct from CARE.
We are dedicated to working together in a nimble program, with our research direction following our discoveries.
Together...

## Key facts

- **NIH application ID:** 10469441
- **Project number:** 5UM1AI164567-02
- **Recipient organization:** UNIV OF NORTH CAROLINA CHAPEL HILL
- **Principal Investigator:** DAVID M. MARGOLIS
- **Activity code:** UM1 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $5,246,834
- **Award type:** 5
- **Project period:** 2021-08-16 → 2026-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10469441

## Citation

> US National Institutes of Health, RePORTER application 10469441, Collaboratory of AIDS Researchers for Eradication (CARE) (5UM1AI164567-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10469441. Licensed CC0.

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