# Revealing Reservoirs during Rebound (R3)

> **NIH NIH P01** · UNIVERSITY OF CALIFORNIA, SAN DIEGO · 2020 · $1,501,059

## Abstract

Abstract
Precisely characterizing HIV rebound when antiretroviral therapy (ART) is stopped can offer valuable insights
into HIV reservoirs including:
 • What biological quantities can predict viral rebound dynamics (timing, set-point, slope),
 • How HIV populates blood cells and anatomic compartments, and
 • What immune mechanisms are associated with HIV population size and activity, rebound characteristics,
 and viral population of circulating CD4+ T cells and tissues.
A sticky clinical research dilemma is that clinical compromise can occur when ART is stopped. To overcome
these dilemmas, the proposed Revealing Reservoirs during Rebound (R3) will:
 • Analyze currently available clinical, virological and immunological data from 504 well-characterized
 participants who started ART during acute and early infection, achieved sustained viral suppression, and
 then interrupted this therapy under monitored studies (Early Treatment Research Project);
 • Generate new virologic and immunologic data from blood samples collected from 60 participants in the
 Zurich Primary Infection cohort and 30 participants in the AIDS Clinical Trials Group study “Identification of
 Biomarkers to Predict Time to Plasma HIV RNA Rebound and Post-Treatment Viral Control during an
 Intensively Monitored Antiretroviral Pause (IMAP)” (A5345) (Early Treatment Research Project);
 • Evaluate 20 altruistic HIV-infected people on ART who are terminally-ill and who have voluntarily decided
 to stop their ART before they die, and who will provide us their blood before and after they stop ART, then
 their bodies after they die (Late Treatment Research Project);
 • These large and diverse sets of data, which will require the development of new analytical methods to
 answer important questions relevant to the HIV cure agenda (Quantitative Methods Research Project).
These three Research Projects will be supported by three Cores.
 • The Administrative Core will ensure effective and efficient management of the program;
 • The Clinical and Pathology Core will ensure appropriate collection and management of R3 specimens;
 • The Quality Assurance and Data Core will ensure quality of data that are collected, generated and
 analyzed across the program.
Altogether, the R3 will address these open questions to provide tangible metrics to guide the development of
HIV cure strategies and inform the use of biomarkers to ascertain whether or not a cure effort has the intended
effect without interrupting ART.

## Key facts

- **NIH application ID:** 9984150
- **Project number:** 5P01AI131385-04
- **Recipient organization:** UNIVERSITY OF CALIFORNIA, SAN DIEGO
- **Principal Investigator:** David Mitchell Smith
- **Activity code:** P01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $1,501,059
- **Award type:** 5
- **Project period:** 2017-08-01 → 2022-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9984150

## Citation

> US National Institutes of Health, RePORTER application 9984150, Revealing Reservoirs during Rebound (R3) (5P01AI131385-04). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9984150. Licensed CC0.

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