Interplay of Autophagy Regulated Cell Death and HIV Pathogenesis in Substance Use Disorders (R01 Clinical Trial Not Allowed) | RFA DA 25 009

Opportunity Information: Apply for RFA DA 25 009

The grant opportunity titled "Interplay of Autophagy Regulated Cell Death and HIV Pathogenesis in Substance Use Disorders (R01 Clinical Trial Not Allowed)" (Funding Opportunity Number RFA-DA-25-009) is a National Institutes of Health (NIH) discretionary research grant that supports mechanistic, hypothesis-driven studies on how autophagy-related pathways of regulated cell death intersect with HIV disease processes in the context of substance use. The scientific emphasis is on the central nervous system (CNS), specifically how acute and chronic exposure to drugs of abuse can shape cellular immune responses in the brain and, in turn, influence HIV pathogenesis. In practical terms, the NOFO is looking for projects that can clarify how drug use alters autophagy and cell-death programs in relevant CNS and immune cell types, and how those changes may contribute to HIV-associated neuroinflammation, viral persistence, neurotoxicity, or other downstream consequences important to HIV disease outcomes.

A central theme of the announcement is "interplay" meaning applicants are expected to connect multiple biological layers rather than study them in isolation. Autophagy is a core cellular homeostatic process involved in degradation and recycling of cellular components, and it can be protective in some settings while contributing to regulated cell death in others. HIV infection and HIV proteins can perturb autophagy pathways, and substances of abuse can also modulate autophagic flux, immune signaling, oxidative stress responses, and glial or neuronal function. This NOFO specifically calls for work that ties those strands together in a coherent model relevant to HIV pathogenesis in people with substance use disorders, with particular attention to CNS cellular immune responses (for example, microglia, astrocytes, infiltrating macrophages, and other immune-relevant cell populations within the brain environment). The intent is to drive deeper understanding of biological mechanisms that could explain why substance use can worsen neurological complications, alter inflammation, or change the trajectory of HIV-related CNS disease, and to identify pathways that might become targets for future therapeutic development (even though this particular opportunity does not permit clinical trials).

The activity mechanism is an NIH R01, which generally supports substantial, multi-year research programs with a defined set of aims and a strong rationale, and the label "Clinical Trial Not Allowed" signals that the funded work must not include prospective assignment of human participants to an intervention to evaluate health-related outcomes. That typically means the application should be built around basic, translational, or preclinical research approaches, such as in vitro systems, animal models, analysis of existing human specimens or datasets (when allowable under NIH definitions and the NOFO terms), or observational and mechanistic human studies that do not meet the NIH definition of a clinical trial. The funding activity category is listed under education and health, and the CFDA number associated with this opportunity is 93.279, indicating alignment with NIH research support in this scientific area.

Eligibility is broad and includes a wide range of organization types that can serve as applicant institutions. Domestic eligible applicants include state, county, city or township, and 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; public housing authorities/Indian housing authorities; Native American tribal organizations other than federally recognized tribal governments; nonprofit organizations both with and without 501(c)(3) status (when not institutions of higher education); for-profit organizations other than small businesses; small businesses; and other eligible entities. The NOFO also explicitly highlights additional eligible applicant categories, including Alaska Native and Native Hawaiian Serving Institutions, Asian American Native American Pacific Islander Serving Institutions (AANAPISIs), Hispanic-serving Institutions, Historically Black Colleges and Universities (HBCUs), Tribally Controlled Colleges and Universities (TCCUs), eligible federal government agencies, faith-based or community-based organizations, regional organizations, U.S. territories or possessions, and non-domestic (non-U.S.) entities (foreign organizations). This breadth signals an interest in attracting a diverse applicant pool and encouraging participation by institutions serving underrepresented or specialized communities, as well as enabling international contributions where scientifically appropriate.

Key administrative details provided include the agency (National Institutes of Health), the funding instrument (grant), the opportunity category (discretionary), and the original closing date of November 14, 2024. The posting indicates that an award ceiling and the expected number of awards were not specified in the excerpted source data, which usually means applicants should rely on the full NOFO for budget guidance, anticipated institute commitment, and any limits or expectations about project period and total costs. The opportunity record shows a creation date of December 6, 2023, which can matter when interpreting policy context, relevant NIH application instructions in effect at the time, and the most current forms and submission requirements.

Overall, this NOFO is essentially a call for rigorous, non-clinical-trial R01 proposals that can explain, at a mechanistic level, how drug use alters autophagy-regulated cell death processes and how those changes influence HIV-related disease biology in the CNS, especially through impacts on cellular immune responses. Applicants are expected to propose research that meaningfully integrates these components and advances understanding of HIV neuropathogenesis and substance use comorbidity, setting the stage for future intervention ideas without directly testing interventions in a clinical trial framework under this specific award.

• The National Institutes of Health in the education, health sector is offering a public funding opportunity titled "Interplay of Autophagy Regulated Cell Death and HIV Pathogenesis in 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 2023-12-06.
• Applicants must submit their applications by 2024-11-14. (Agency may still review applications by suitable applicants for the remaining/unused allocated funding in 2026.)
• 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.

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