Exploratory studies to investigate mechanisms of HIV infection, replication, latency, and/or pathogenesis in the context of substance use disorders (R01 Clinical Trial Not Allowed) | RFA DA 25 011

Opportunity Information: Apply for RFA DA 25 011

The National Institutes of Health (NIH) is offering a discretionary grant opportunity titled "Exploratory studies to investigate mechanisms of HIV infection, replication, latency, and/or pathogenesis in the context of substance use disorders (R01 Clinical Trial Not Allowed)" under Funding Opportunity Number RFA-DA-25-011 (CFDA 93.279). This request for applications is designed to fund exploratory, mechanistic research that deepens understanding of how substance use disorders (SUDs) intersect with core biological processes of HIV, including viral infection, replication, establishment and maintenance of latency, and downstream disease mechanisms. The scope explicitly includes HIV-associated neurocognitive disorders (HAND), signaling that studies focused on neurologic and neurobehavioral consequences and their underlying biology are within bounds so long as they remain mechanistic rather than clinical trial oriented.

The scientific emphasis is on causative mechanisms rather than descriptive epidemiology or intervention testing. Projects are expected to ask focused, hypothesis-driven questions about how substances of misuse, patterns of substance exposure, or SUD-related biological and behavioral factors influence HIV at the cellular, tissue, and systems levels. In practice, that can include work on host-pathogen interactions, immune modulation, inflammation, neuroimmune pathways, viral reservoir dynamics, and molecular or cellular pathways that affect latency and reactivation, particularly where substance use meaningfully alters these processes. Because the FOA is labeled "Clinical Trial Not Allowed," applications must avoid proposing clinical trials; in general, that means no prospective assignment of human participants to interventions to evaluate health-related outcomes. Mechanistic studies may still involve human samples or observational human research where appropriate, but the research plan must not cross into interventional clinical trial territory.

The funding instrument is an R01 research project grant, indicating support for substantial, investigator-initiated research programs consistent with NIH R01 expectations, but with an exploratory, mechanism-focused framing for this specific competition. The listed award ceiling is $700,000, which sets an upper bound on the amount available under the opportunity as presented in the source data. The opportunity was created on 2023-10-05, and the original closing date is 2025-08-14, establishing the submission deadline for applications under this announcement.

Eligibility is broad and intentionally inclusive of many organization types that can contribute to HIV and SUD mechanistic research. Eligible applicants include state, county, and city or township governments; special district governments; independent school districts; public and state-controlled institutions of higher education; private institutions of higher education; federally recognized Native American tribal governments; native American tribal organizations other than federally recognized tribal governments; public housing authorities and Indian housing authorities; nonprofit organizations with or without 501(c)(3) status (excluding institutions of higher education in those nonprofit categories as specified); for-profit organizations other than small businesses; and small businesses. In addition, the opportunity explicitly calls out a wide range of other eligible applicant categories, including Alaska Native and Native Hawaiian Serving Institutions, Asian American Native American Pacific Islander Serving Institutions (AANAPISI), Hispanic-serving Institutions, Historically Black Colleges and Universities (HBCUs), Tribally Controlled Colleges and Universities (TCCUs), eligible agencies of the federal government, faith-based or community-based organizations, Indian/Native American tribal governments other than federally recognized, regional organizations, U.S. territories or possessions, and non-domestic (non-U.S.) entities (foreign organizations). Taken together, this eligibility language signals an intent to encourage applications from diverse institutional settings, including minority-serving institutions, community-engaged organizations, and international research entities where scientifically justified.

Overall, this RFA is best read as a call for rigorous laboratory, translational, and mechanistic studies that clarify how substance use and SUD biology change the trajectory of HIV infection and disease, including neurologic complications like HAND, without moving into clinical trial testing of interventions. Applicants would be expected to define clear mechanistic aims, use appropriate models or biospecimens, and articulate how their findings will advance understanding of HIV persistence, pathogenesis, and SUD-related modifiers in ways that can ultimately inform future prevention and treatment strategies, even if the proposed work itself is not an intervention trial.

• The National Institutes of Health in the education, health sector is offering a public funding opportunity titled "Exploratory studies to investigate mechanisms of HIV infection, replication, latency, and/or pathogenesis in the context of substance use disorders (R01 Clinical Trial Not Allowed)" and is now available to receive applicants.
• Interested and eligible applicants and submit their applications by referencing the CFDA number(s): 93.279.
• This funding opportunity was created on 2023-10-05.
• Applicants must submit their applications by 2025-08-14. (Agency may still review applications by suitable applicants for the remaining/unused allocated funding in 2026.)
• Each selected applicant is eligible to receive up to $700,000.00 in funding.
• Eligible applicants include: State governments, County governments, City or township governments, Special district governments, Independent school districts, Public and State controlled institutions of higher education, Native American tribal governments (Federally recognized), Public housing authorities/Indian housing authorities, Native American tribal organizations (other than Federally recognized tribal governments), Nonprofits having a 501 (c) (3) status with the IRS, other than institutions of higher education, Nonprofits that do not have a 501 (c) (3) status with the IRS, other than institutions of higher education, Private institutions of higher education, For-profit organizations other than small businesses, Small businesses, Others.

Apply for RFA DA 25 011

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