# Project 3: Viral dynamics of Remission or Rebound Following Early Treatment of SIV

> **NIH NIH P01** · BOSTON COLLEGE · 2021 · $345,976

## Abstract

ABSTRACT
The suppression 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. However, despite the sustained suppression of plasma viremia below detectable limits in infected
patients for many years on ART regimens, replication competent virus can still be recovered from a variety of
sites within the host, and most notably from long-lived quiescent memory CD4+ T lymphocytes. This viral
reservoir represents the final impediment to the eradication and clearance of HIV infection or to a sustained
virologic remission in the absence of ART. Currently, our understanding of HIV reservoirs in ART recipients is
incomplete. Data assessing the impact of early ART initiation during acute infection on reservoir size are
limited, especially in the tissues, as are virologic and immunologic surrogates of remission or control of HIV-1.
Recent data from my laboratory has shown that persistent viral reservoirs are established very early in SIV
infection [1]. However, very early ART can limit the seeding and expansion of cellular reservoirs of HIV [2-4].
Moreover, ART initiated in the earliest stages could significantly limit the size, location and genetic diversity of
the HIV-1 reservoir, thereby improving the chance of a virologic remission. The efficacy of potent latency
reversal agents (LRAs) or other immunotherapy delivered to very these early ART-treated reservoirs is
unclear.
Thus, detailed mechanistic studies are needed to define the impact of early ART on virological and
immunologic outcomes that are relevant to achieving HIV remission and durable virus control after the
cessation of ART [5]. Such investigations are detailed in this proposal.
To investigate these hypotheses, we propose the following Specific Aims:
1. Determine the impact of early ART on the nature and distribution of the SIV reservoir during early
viral establishment.
2. Assess SIV distribution and clonal expansion during ART initiation and after ART cessation.
3. Determine the impact of combination immunotherapy (TLR7 agonist and PD-L1) on the stability
of the viral reservoir after ART cessation.

## Key facts

- **NIH application ID:** 10246903
- **Project number:** 7P01AI131365-05
- **Recipient organization:** BOSTON COLLEGE
- **Principal Investigator:** James Burton Whitney
- **Activity code:** P01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $345,976
- **Award type:** 7
- **Project period:** 2017-08-11 → 2024-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10246903

## Citation

> US National Institutes of Health, RePORTER application 10246903, Project 3: Viral dynamics of Remission or Rebound Following Early Treatment of SIV (7P01AI131365-05). Retrieved via AI Analytics 2026-05-21 from https://api.ai-analytics.org/grant/nih/10246903. Licensed CC0.

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