# Targeting the HIV/SIV reservoir at time of ART initiation

> **NIH NIH R01** · OREGON HEALTH & SCIENCE UNIVERSITY · 2020 · $687,893

## Abstract

PROJECT SUMMARY
Antiretroviral therapy (ART) has dramatically improved the prognosis of people living with human
immunodeficiency virus (HIV) infection. However, ART alone cannot eradicate the infection and therefore, daily
treatment must be maintained for life to prevent relapse of uncontrolled viral replication and resumption of
disease progression. Unfortunately, in addition to persistent stigma associated with HIV infection, lifelong
treatment entails both health risks to treated individuals and a significant economic burden to society. As such,
there is a desperate need to develop novel therapeutic interventions that can cure HIV infection. It is now well
established that initiation of ART in the first days/weeks after infection does not prevent the establishment of a
long-lived viral reservoir, although it is effective at reducing its size. Another strategy aimed at reducing the
reservoir is to induce HIV gene expression in individuals on suppressive ART with the goal of eliminating latently
infected cells, which could ultimately lead to virus eradication. However, purging the HIV reservoir not only
requires the induction of viral replication by latency-reversing agents (LRA) but also the elimination of these
reactivating latently-infected cells by either viral cytopathic effects or immune cell-mediated killing, so called
“shock and kill”. This killing is often inefficient when LRAs are administered to HIV-infected individuals after
several years of ART, possibly due to low level antigen expression, negative impact of LRAs on clearance
mechanisms or the low frequencies of effective HIV-specific CD8+ T cells. Here we propose to evaluate a novel
strategy in which an LRA is administered together with ART during acute infection. We believe this “window of
opportunity” when the immune responses are still present and the latent reservoir is easier to reactivate will
improve the efficacy of the “shock and kill HIV” approach to a cure. To address this, we will use GSK445A, a
stabilized Ingenol-B based Protein Kinase C agonist (PKC) that we have shown can induce HIV/SIV transcription
in vitro and in vivo in SIV-infected rhesus macaques (RM) on ART without significant toxicity. We propose to
further optimize our strategy by evaluating if combining GSK445A with IL-15 can enhance the therapeutic effect.
As such, the goal of this R01 is to determine whether administering this potent LRA during acute SIV infection,
at the time of ART initiation, will delay or prevent viral rebound after ART cessation. The demonstration of
therapeutic efficacy in this project will provide strong impetus for assessment of this concept in recently infected
HIV+ individuals.

## Key facts

- **NIH application ID:** 10101853
- **Project number:** 1R01AI147749-01A1
- **Recipient organization:** OREGON HEALTH & SCIENCE UNIVERSITY
- **Principal Investigator:** Afamefuna Okoye
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $687,893
- **Award type:** 1
- **Project period:** 2020-07-23 → 2024-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10101853

## Citation

> US National Institutes of Health, RePORTER application 10101853, Targeting the HIV/SIV reservoir at time of ART initiation (1R01AI147749-01A1). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10101853. Licensed CC0.

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