# The effects of opioid use on HIV-1 reservoir dynamics

> **NIH NIH R61** · BRIGHAM AND WOMEN'S HOSPITAL · 2020 · $1,066,790

## Abstract

Abstract
 HIV-1 persists in memory CD4+ T cells during suppressive antiretroviral therapy (ART) and is the major
barrier to virus cure. Ultimately, a successful HIV eradication approach will need to work equally well regardless
of disease stage, underlying immune system function, or medical comorbidities.
 People with HIV are commonly exposed to opioids, whether prescribed for chronic pain,
prescribed for opioid use disorder, or injected as heroin. Opioid exposure has demonstrated immune modulatory
effects but the impact of opioids on HIV-1 reservoir dynamics has not been studied and thus there is an urgent
need for focused, mechanistic studies to address this critical knowledge gap. The purpose of this proposal is to
apply cutting-edge experimental approaches to understand precisely how opioids and opioid use disorders
impact HIV-1 reservoir dynamics and latency reversal and transform our ability to study and test HIV-1
eradication approaches in this important patient population. The scientific premise of this proposal is that opioids
limit HIV-1 transcriptional and translational reactivation due to a previously unrecognized block in RNA and
protein synthesis.
 While the HIV eradication field has focused on transcriptional biomarkers of latency reversal, our
preliminary ribosome profiling data reveals that translation, not transcription, is the rate-limiting step in HIV-1
reactivation. Ribosome profiling is a novel technique that uses deep sequencing to characterize the nuclease-
protected footprints of ribosomes on mRNA transcripts in vivo. Protein synthesis can be monitored genome-wide
and when combined with mRNA sequencing (mRNA-seq) provides a quantitative measure of translation
efficiency. We propose to leverage HIV and host genomic information and investigate the mechanisms that
control HIV-1 latency reversal in patients using opioids. We hypothesize that opioid use will limit HIV-1 latency
reversal and lower HIV-1 translation efficiencies, when compared to HIV-1 latency reversal in the absence of
opioid exposure. To define the effects of opioids on traditional HIV-1 persistence markers in vivo, we will perform
a cross-sectional analysis among HIV-infected treated suppressed participants and quantify and compare
traditional HIV-1 persistence markers from 5 groups: individuals who are 1) actively injecting opioids (n=20), 2)
on methadone maintenance (n=20), 3) on buprenorphine maintenance (n=20), 4) on prescribed opioids for
chronic pain treatment (n=20), and 5) on no opioids (n=40). We will perform ex vivo reactivation experiments
with participants' PBMC and a panel of LRA. LRA-induced levels of HIV-1 caRNA and supernatant virion
production will be compared across opioid use groups. To accurately measure genome-wide host and HIV-1
translation in PBMC isolated from patients who use opioids, parallel mRNA-seq and ribosome profiling will be
performed. Finally, we will assess longitudinal HIV-1 reservoir dynamics in a group of 40 participants ...

## Key facts

- **NIH application ID:** 9929567
- **Project number:** 5R61DA047038-03
- **Recipient organization:** BRIGHAM AND WOMEN'S HOSPITAL
- **Principal Investigator:** Nina H. Lin
- **Activity code:** R61 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $1,066,790
- **Award type:** 5
- **Project period:** 2018-08-15 → 2022-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9929567

## Citation

> US National Institutes of Health, RePORTER application 9929567, The effects of opioid use on HIV-1 reservoir dynamics (5R61DA047038-03). Retrieved via AI Analytics 2026-05-27 from https://api.ai-analytics.org/grant/nih/9929567. Licensed CC0.

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