# Enterprise for Research and Advocacy to Stop and Eradicate HIV (ERASE-HIV)

> **NIH NIH UM1** · EMORY UNIVERSITY · 2022 · $5,412,341

## Abstract

Abstract
The presence of a reservoir of cells harbouring integrated, replication-competent virus that persists under long-
term, fully suppressive antiretroviral therapy (ART) and the inability of the host immune responses to control the
initial events of viral replication that follow ART interruption are critical barriers to curing HIV infection. Thus,
novel therapeutic strategies to remove these barriers are critically needed. The overarching hypotheses of
ERASE HIV are: (i) decreased and/or dysfunctional CD8+ T and NK cell antiviral functions, combined with the
recently-described CD8+ T-cell-mediated transcriptional silencing of HIV, favour HIV persistence under ART and
prevent the control of viremia if ART is stopped; and (ii) novel approaches to elicit effective CD8+ T-cell, NK cell,
and antibody-dependent cellular cytotoxicity (ADCC) functions while inhibiting the CD8+ T-cell-mediated virus
silencing will promote remission and/or eradication of HIV. The overarching goal of ERASE HIV is to identify
novel mechanisms of HIV persistence and to test them in the most relevant pre-clinical animal models through
mechanistically-oriented, community-supported therapeutic strategies that can be ultimately translated to cure
HIV infection in humans. ERASE HIV includes three highly integrated Research Foci (RFs). RF1 is aimed at
identifying the molecular and cellular mechanisms underlying the two distinct antiviral activities of CD8+ T-cells:
the MHC-restricted, Ag-specific response that directly eliminates virus-infected cells, and the non-MHC
restricted, non-cytolytic silencing of HIV transcription. As such, RF1 will provide the conceptual basis for the
interventions tested in RF2 and RF3. RF2 will use animal models of ART-treated HIV infection to (i) restore CD8+
T and NK cell function with a combined α-IL-10 and IL-15 superagonist (N-803) strategy; (ii) target rebounding
virus by using a CD4-mimetic compound (CD4mc) to enhance antibody recognition of cells expressing HIV Env
and their elimination via ADCC; and (iii) determine if improving CD8 T and NK cell function via α-IL-10 and N-
803 synergizes with CD4mc to clear infected cells. RF3 will determine if suppression of the latency-promoting
activity of CD8+ T-cells, coupled with N-803 and interventions to promote apoptosis (Bcl-2 inhibitors) or immune-
mediated removal (CD4mc) of cells that have reactivated virus, will reduce the reservoir size. In all, we will exploit
the synergy between the mechanistic data generated in RF1 and the in vivo interventions in RF2 and RF3 to
validate a strategy that targets both HIV persistence during ART and HIV recrudescence after ART interruption.
ERASE HIV is supported by experts in HIV advocacy (SisterLove); recognition and killing of HIV Env-expressing
cells (Finzi/Sodroski); T and NK cell biology (Sekaly/Ribeiro/Deleage/Parsons); reservoir assays and latency
models (Kulpa/Jones/Litchterfeld/Howell); pre-clinical animal studies (Paiardini/Silvestri/Garcia/Saez-...

## Key facts

- **NIH application ID:** 10469504
- **Project number:** 5UM1AI164562-02
- **Recipient organization:** EMORY UNIVERSITY
- **Principal Investigator:** Deanna A Kulpa
- **Activity code:** UM1 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $5,412,341
- **Award type:** 5
- **Project period:** 2021-08-16 → 2026-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10469504

## Citation

> US National Institutes of Health, RePORTER application 10469504, Enterprise for Research and Advocacy to Stop and Eradicate HIV (ERASE-HIV) (5UM1AI164562-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10469504. Licensed CC0.

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