Development and Testing of Novel Interventions to Improve HIV Prevention, Treatment, and Program Implementation for People Who Use Substances (R34 Clinical Trial Required)

The National Institutes of Health (NIH), through its component agency the National Institute on Drug Abuse (NIDA), has reissued a funding opportunity to support the development and pilot testing of novel or adapted interventions targeting HIV prevention, treatment, and implementation for populations affected by substance use. This initiative, under the R34 Planning Grant mechanism, supports early-phase clinical trials, specifically encouraging the creation and feasibility testing of interventions designed to address HIV-related outcomes in individuals who use substances. It is aimed at improving health equity by integrating strategies that can engage high-risk populations more effectively in HIV care, prevention, and treatment services. This notice of funding opportunity (NOFO) seeks to advance both the science and practical application of HIV prevention and care, particularly by addressing the intersection between substance use and HIV. Applicants may propose studies that address feasibility, acceptability, and safety of behavioral, social, structural, or combination interventions. These interventions may be adapted from existing models or newly developed to suit novel populations or contexts. Examples include seek/test/treat/retain strategies, new PrEP formulations, telehealth innovations, and syndemic-focused interventions targeting co-occurring disorders, such as mental illness and substance use. The program prioritizes efforts that incorporate input from end users—such as community members, policymakers, practitioners—to ensure relevance, sustainability, and scalability. Eligible activities include pilot or feasibility trials in domestic or international settings, with a focus on populations bearing a disproportionate burden of HIV, such as people who inject drugs (PWID), men who have sex with men (MSM), and other key groups where stimulant or polysubstance use is prevalent. Applicants must provide a strong scientific rationale, including a logic model or theory of change, even in the absence of preliminary data. End-user involvement must be clearly demonstrated, and interventions must be conceived with implementation potential in mind, including adaptability to real-world service systems. Funding details specify that applicants may request up to $450,000 in direct costs over a three-year project period, with no more than $225,000 in any single year. Awards are contingent upon NIH appropriations and the merit of submitted proposals. There is no cost-sharing requirement. Eligible applicants include a wide array of U.S. and foreign organizations, such as public and private higher education institutions, nonprofits, for-profit organizations, tribal entities, and foreign institutions. Collaborative and community-engaged approaches are encouraged, and applicants are required to comply with multiple NIH policies including those related to data sharing, clinical trials, and human subjects research. Submissions must be made electronically via one of the NIH-supported platforms (ASSIST, Grants.gov Workspace, or institutional S2S systems), with appropriate registrations completed in SAM, Grants.gov, eRA Commons, and related systems. Applications will be reviewed based on overall impact, importance of the research, feasibility, rigor, and investigator and institutional capability. Special emphasis will be placed on the inclusion of end users and community expertise in the research design and execution. The opportunity is open for applications starting April 7, 2025. It accepts AIDS-related proposals on three standard dates annually: May 7, September 7, and January 7. This funding announcement expires May 8, 2026, aligning with recent NIH changes. Awards are expected approximately eight months after submission deadlines, with earliest start dates in December 2025 for May submissions. Contact persons at NIDA include Dr. Richard Jenkins, Candace Webb, and Dr. Raul Mandler, whose emails and phone numbers are listed for scientific inquiries. The program remains a vital mechanism for improving the interface of substance use treatment and HIV-related health services, advancing public health priorities both domestically and globally.