NIH – PrEP for HIV Prevention among Substance Using Populations (R01 – Clinical Trial Optional)

June 25, 2021 by


NIDA is interested in research that addresses research gaps related to PrEP and its use among people who use drugs (PWUD), with the goals of improving PrEP uptake, adherence and implementation. Current US Public Health Service PrEP guidelines recommend PrEP for people who inject drugs (PWID) and mention alcohol and illicit drug use as potential concerns for clinical management. More systematic data are needed regarding the impact of substance use on PrEP management and adherence, as well as the best ways to deliver PrEP and integrate it with other services. Recent trials have demonstrated the efficacy of injectable Cabotegravir as PrEP, although no data exist for PWUD and there is a need to inform the best practices for delivery and management of injectable PrEP among PWUD, as well as for oral PrEP. This RFA is restricted to projects conducted in the United States. Applications are encouraged that propose research in states and counties identified in the US Government’s Ending the HIV Epidemic (EHE) initiative. Applications to work in locales that are not included in the EHE initiative must provide an epidemiologic justification for their inclusion in the research.


Systematic data regarding the use of PrEP among people who use drugs (PWUD) remain limited, and data are lacking with respect to PWUD among a variety of key populations with relatively high levels of substance use such as MSM, transgender persons and sex workers. One efficacy trial has evaluated PrEP among people who inject drugs (PWID). That trial recruited from methadone clinics in Bangkok and found 49% fewer new HIV cases in the vaccine arm but had limited data on drug use or injection. An open-label follow-up study found relatively low levels of reported sexual risk, drug use and injection which suggested some ambiguity regarding PrEP efficacy among PWID. Current US Public Health Service guidelines do not address the limits of available evidence for PrEP for PWUD. The guidelines mention the Bangkok trial among PWID without attending to the consequences of the limited available data. The use of alcohol and illicit drugs is otherwise mentioned as a potential concern for clinical management, with a recommendation for referral to substance abuse treatment or harm reduction services, but not addressing the ongoing management of PrEP among PWUD. PrEP research among PWUD has begun to emerge in recent years and PrEP providers have begun addressing the need to reach PrEP users in a diverse range of populations. Nonetheless, available data indicate that PrEP awareness is, at best, moderate among PWUD and uptake remains low.

NIDA seeks to address gaps in our knowledge about PrEP among substance users that can ultimately inform clinical practice, including gaps related to basic clinical research, PrEP performance in PWUD, and research to improve implementation practice. PrEP research and practice has been moving in the direction of addressing questions about optimal approaches for implementation, including service delivery methods, setting/organizational considerations, and integration with other prevention services. PrEP research can benefit from the experience with Anti-Retroviral Treatments (ARTs) among PWUD. Research on ARTs for HIV treatment suggests that medication adherence is lower among substance users, and that navigation and case management approaches often perform less well than in people who are not using drugs. Contemporary ARTs appear not to have interactions with illicit drugs that were observed with earlier HIV treatments, but the effects of substances of abuse have not been tested with PrEP, particularly in the context of managing consequences of substance use (e.g., infections related to poor care or shared equipment).

Recent trials with injectable Cabotegravir suggest that this approach can be more efficacious than daily oral PrEP; however, injectable treatment and prevention agents for other conditions often have underperformed initial expectations and had uptake limited to rather specific contexts. Injectable PrEP has not been subjected to clinical trials among people who use drugs and research is needed which can clinical research questions and inform practice guidelines for PWUD.

Implementation of PrEP among PWUD may require tailored forms of engagement, monitoring, management and long-term retention in care, including stepped intervention approaches to address problems with PrEP uptake and persistence or the need to address HIV risk among people who do not initiate PrEP use. Tailored implementation strategies may be particularly important among persons with substance use disorders, especially those who are not actively seeking treatment and those who share injection equipment or drug preparation. Settings that provide services such as drug treatment or needle exchange may provide opportunities to engage substance users but may need specialized intervention approaches to facilitating monitoring and long-term management.

Key Dates:

Open Date (Earliest Submission Date): October 12, 2021
Letter of Intent Due Date: October 12, 2021
Application Due: November 12, 2021

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Filed Under: Funding Opportunities