# Dynamics, immune responses, and transcriptomics of the HIV-expressing reservoir on ART

> **NIH NIH P01** · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · 2022 · $399,583

## Abstract

Project Summary/Abstract (Project #1)
 To develop new therapies aimed at HIV cure or reducing the sequelae of ART-treated infection, there is
a critical need for more research on the persistence of HIV-infected cells that can contribute to immune activation
on ART and allow virologic rebound after ART interruption. While the rebound competent reservoir is often
assumed to be the same as the latent and/or the intact reservoir, sequences from the rebound virus usually do
not match those from the latent reservoir but sometimes match those from cell-associated HIV RNA prior to ART
interruption. These findings suggest the need to better understand the reservoirs that express HIV in vivo, which
are poised to initiate rebound on interruption of ART and likely contribute to the immune activation, organ
damage, and reduced life expectancy on ART. However, prior studies of the “transcriptionally active reservoir”
have not been able to fully characterize the heterogeneity of these cells, which vary in terms of the types of HIV
RNA transcribed (processive or complete, from defective or intact proviruses) and whether it is translated into
HIV protein. We hypothesize that subsets of cells expressing different types of HIV RNA and/or protein will differ
in terms of their frequency, survival/clearance rate, contribution to immune activation, cellular gene expression,
and tissue distribution. To investigate these hypotheses, this project will apply a series of new and cutting-edge
assays to longitudinal samples fromdifferent clinical phenotypes in order to: 1) measure how different proviruses
(intact/defective), blocks to HIV transcription, defective or intact HIV transcripts, and HIV Gag protein change
over time pre- and post-ART in the blood and how they differ between elite controllers and individuals who initiate
ART during acute or chronic infection; 2) determine how levels of each type of HIV RNA and protein correlate
with HIV-specific T and other immune responses as well as markers of immune activation/inflammation; and 3)
determine how differential expression of host cell genes (such as antiviral factors) relates to the ability of these
cells to express HIV and survive in blood and lymph nodes. Subsequent projects will investigate how different
types of proviruses and HIV-expressing cells differ in their frequencies, phenotypes, and viral/cellular gene
expression throughout the full spectrum of tissues in the body (Project #2), and how they differ in their
contribution to rebound and susceptibility to novel therapies designed to target and kill HIV-expressing cells
(Project #3).

## Key facts

- **NIH application ID:** 10459932
- **Project number:** 1P01AI169606-01
- **Recipient organization:** UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
- **Principal Investigator:** Steven A Yukl
- **Activity code:** P01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $399,583
- **Award type:** 1
- **Project period:** 2022-05-01 → 2027-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10459932

## Citation

> US National Institutes of Health, RePORTER application 10459932, Dynamics, immune responses, and transcriptomics of the HIV-expressing reservoir on ART (1P01AI169606-01). Retrieved via AI Analytics 2026-05-27 from https://api.ai-analytics.org/grant/nih/10459932. Licensed CC0.

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