# Taking Our Shot: Extended-Release Naltrexone as Opioid Overdose Pre-Exposure Prophylaxis (PrEP) in People Using Stimulants Living With or At Risk of HIV

> **NIH NIH DP2** · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · 2024 · $2,460,000

## Abstract

PROJECT SUMMARY
Cocaine and methamphetamine-related deaths have risen steeply in the United States, the majority associated
with fentanyl. Stimulant use is prevalent among people living with or at risk for HIV, and in this population, it is
unknown what proportion of mixed stimulant-opioid overdose deaths are due to unintentional fentanyl
exposure. As overdose deaths threaten gains in life expectancy among PWH in recent years, we need to use
all available tools at our disposal to prevent unintentional opioid exposure and overdose. We propose a novel
concept of opioid overdose pre-exposure prophylaxis (PrEP) for individuals using stimulants and living with or
at risk for HIV. We will perform a randomized controlled trial of a long-acting injectable opioid antagonist
(intramuscular naltrexone) vs. a conventional in-clinic harm reduction bundle, with stratified randomization
based on baseline antiretroviral therapy delivery strategy (i.e., injectable vs. oral HIV prevention/treatment).
Our three key objectives are: 1) investigate the feasibility, acceptability, and preliminary effectiveness of
intramuscular naltrexone as a preventive measure for opioid overdose in individuals using stimulants, 2)
capture the experiences of patients receiving concurrent long-acting injectable medicines for HIV and
substance use, 3) employ short and long-term biomarkers of substance use, supplemented by participant
interviews, to craft an epidemiological profile detailing intentional and unintentional opioid exposure among
individuals living with or at risk of HIV. Our creative approach repurposes intramuscular naltrexone,
conventionally used for opioid and/or alcohol use disorders, as an innovative method for opioid overdose
prevention. This trial will be performed at University of California San Francisco (UCSF) at San Francisco
General Hospital’s Ward 86 clinic, home to the largest known cohort of people who use drugs receiving long-
acting injectable HIV treatment/prevention. San Francisco county's high per capita overdose death rate
underscores the urgent need for our research, and our study promises to provide valuable insights into the
interplay of HIV prevention/treatment, stimulant use, and opioid overdose prevention.
.

## Key facts

- **NIH application ID:** 10908084
- **Project number:** 1DP2DA060600-01
- **Recipient organization:** UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
- **Principal Investigator:** Ayesha A Appa
- **Activity code:** DP2 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $2,460,000
- **Award type:** 1
- **Project period:** 2024-07-01 → 2028-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10908084

## Citation

> US National Institutes of Health, RePORTER application 10908084, Taking Our Shot: Extended-Release Naltrexone as Opioid Overdose Pre-Exposure Prophylaxis (PrEP) in People Using Stimulants Living With or At Risk of HIV (1DP2DA060600-01). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10908084. Licensed CC0.

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