# Effect of opioid use disorder on HIV latent reservoirs and immune dysfunction assessed by single-cell transcriptomics

> **NIH NIH R33** · BOSTON UNIVERSITY (CHARLES RIVER CAMPUS) · 2021 · $911,136

## Abstract

Project Summary
Approximately 12 million people inject drugs globally; 13% of whom are people living with HIV (PLWH). Opioid
misuse is a route of HIV acquisition and a barrier to effective antiretroviral therapy (ART). However, it is
unclear whether opioid misuse changes the course of HIV pathogenesis and latency. Latency is a barrier to
curing HIV because it results in a reservoir of infected quiescent cells that evade the antiviral immune
response, are not targeted by ART, and allow HIV viremia to rebound upon treatment interruption. Latent cells
are rare and lack identifying biomarkers, making it challenging to quantify and characterize the latent cell
reservoir.
Our central hypothesis is that opioid misuse exacerbates HIV pathogenesis and the establishment of HIV
latency by dysregulating the host immune response. Our overall objective is to exploit transcriptomic
information from patient samples to characterize the effects of opioid use disorder on host immune function,
HIV replication, and HIV latency. We will leverage four existing NIDA- and NIAAA-funded studies in St.
Petersburg, Russia whose participants have well-characterized opioid use.
In the R61 phase, we will characterize single cell gene expression and identify dysregulated gene regulatory
networks in immune cells associated with opioid misuse in PLWH. We will also perform computational analysis
to identify immune cell gene regulatory networks altered by opioid misuse (Aim 1). Next, we will combine single
cell RNA-seq and fluorescent in situ hybridization flow cytometry (flow-FISH) to characterize the transcriptome
in cell models of latent HIV infection (Aim 2).
In the R33 phase, we will use tools developed and optimized in Aim 2 to characterize the latent reservoir in
PLWH with and without opioid misuse. We will also validate whether immune cell gene networks altered by
opioid misuse influence HIV transcription and replication (Aim 3). Lastly, we will use predictions from
computational analysis in Aim 1 to test candidate molecules for their ability to influence HIV transcription and
latency among PLWH with and without opioid use.
Successful completion of these aims will have significant research and clinical impact by: 1) elucidating how
opioid misuse alters HIV pathogenesis; 2) producing novel tools for characterizing HIV latency; and 3)
discovering candidate molecules to regulate HIV expression in the context of opioid misuse.

## Key facts

- **NIH application ID:** 10383913
- **Project number:** 4R33DA047032-04
- **Recipient organization:** BOSTON UNIVERSITY (CHARLES RIVER CAMPUS)
- **Principal Investigator:** Christine Cheng
- **Activity code:** R33 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $911,136
- **Award type:** 4N
- **Project period:** 2018-08-15 → 2023-05-24

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10383913

## Citation

> US National Institutes of Health, RePORTER application 10383913, Effect of opioid use disorder on HIV latent reservoirs and immune dysfunction assessed by single-cell transcriptomics (4R33DA047032-04). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10383913. Licensed CC0.

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