The National Institute on Drug Abuse (NIDA) has issued a Notice of Funding Opportunity (NOFO) for R01 grants to support innovative research investigating mechanisms of HIV infection, latency, replication, and pathogenesis within the context of Substance Use Disorders (SUDs). This program seeks high-risk, high-impact studies that develop or apply new tools and technologies or test novel hypotheses in understanding HIV’s effects in the central nervous system (CNS), particularly as influenced by addictive substances. Research should focus on the molecular mechanisms by which HIV is initiated, established, and sustained within the CNS, with an emphasis on how SUDs impact HIV infection and latency, as well as on the effects of antiretroviral therapy (ART) in individuals with SUDs.

This funding opportunity prioritizes studies that explore specific HIV/SUD mechanisms in brain or CNS-relevant systems, using samples or models related to human or primate immune systems. Research should investigate how addictive substances such as opioids, cannabinoids, nicotine, stimulants, or prescription drugs influence HIV latency, neuroinflammation, and viral reservoirs in the CNS. Studies may involve analyses of patient samples or preclinical models but should avoid focusing on alcohol alone. NIDA encourages studies that leverage bio-specimens from existing cohorts and collaborative approaches that integrate expertise across HIV, neuroscience, and addiction research fields.

Eligibility is open to higher education institutions, nonprofits, for-profits, government entities, tribal organizations, and foreign entities. Collaborative applications are encouraged, and investigators should outline a clear communication plan. The total budget per application may not exceed $700,000 per year in direct costs, with a maximum project period of five years. Funding is anticipated for up to three awards, contingent on available appropriations and the quality of applications. Applications are required to be milestone-driven, and applicants should provide detailed, quantitative milestones and timelines to measure progress annually.

Applications must include at least one aim addressing HIV mechanisms in the context of addictive substance pathways and one aim involving human, primate, or humanized models. Key components also include a “Milestones and Timeline” section, outlining project objectives and potential challenges. NIDA emphasizes studies that move beyond incremental advancements and open new avenues for prevention, diagnosis, and therapeutic efforts. Proposals may include preliminary data, though it is not mandatory; a strong scientific premise based on existing literature is sufficient.

The application deadline is August 14, 2025. Interested applicants are encouraged to submit a Letter of Intent by July 14, 2025, although it is not required. Applications must follow NIH’s application guidelines and be submitted via Grants.gov, with SAM, eRA Commons, and Grants.gov registrations completed well in advance. NIDA staff are available for inquiries, and applicants are required to attend an annual in-person meeting for the duration of the award. Applications will be reviewed on criteria including innovation, rigor, feasibility, and alignment with NIDA’s mission to advance understanding of HIV/SUD interactions.