This Notice of Funding Opportunity (NOFO), issued by the National Institute on Drug Abuse (NIDA) under the National Institutes of Health (NIH), supports the development and pilot testing of innovative interventions targeting HIV prevention, treatment, and service delivery among people who use substances. Applications under this R34 mechanism must include a clinical trial, and projects are expected to evaluate the feasibility, acceptability, and safety of new or adapted interventions. Funded studies may focus on behavioral, social, structural, or biomedical approaches that address the specific needs of populations where substance use significantly contributes to HIV risk or impacts care outcomes.

Research topics may include interventions to improve PrEP uptake and adherence, address syndemic factors like co-occurring substance use and psychiatric disorders, or integrate HIV prevention and treatment into non-traditional settings. Studies can explore structural barriers to care, the impact of stigma, and approaches to reduce disparities in access to HIV prevention and treatment services. Projects should engage end users—such as policymakers, practitioners, and community members—in study design and implementation to ensure scalability and sustainability of interventions. Applications must align with NIH and NIDA HIV/AIDS research priorities and include a robust Plan for Enhancing Diverse Perspectives (PEDP).

Eligible applicants include public and private higher education institutions, nonprofits, for-profit organizations, governments, and international entities. Applicants must demonstrate the availability of resources and expertise to conduct the proposed research and adhere to NIH registration requirements, including SAM, Grants.gov, and eRA Commons. The total project budget is capped at $450,000 in direct costs for a maximum period of three years, with no more than $225,000 in any single year.

Applications should include a clear theory of change or logic model, evidence of feasibility through prior collaborations or experience, and plans for assessing intervention fidelity and scalability. Preliminary data is not required but should include strong scientific rationale. Studies should provide a well-justified approach, including methodology for the clinical trial and any proposed comparison group.

Applications will be evaluated for scientific and technical merit by peer review, focusing on the significance, innovation, and feasibility of the research. The PEDP will be assessed as part of the overall impact score. Applications are due by 5:00 PM local time of the applicant organization, with standard NIH submission deadlines applicable. The first due date is May 7, 2025, for a December 2025 earliest start date. Applications missing required elements, including the PEDP, will not be reviewed.

This funding opportunity aims to foster novel solutions to persistent challenges in addressing HIV in substance-using populations. Applicants are encouraged to engage with NIDA program officials to ensure their project aligns with the goals of this NOFO and to clarify any requirements. Further details are provided in the NIH Grants Policy Statement and accompanying NOFO documentation.