Targeting Inflammasomes in HIV and Substance Use (R21 Clinical Trial Not Allowed) | RFA DA 25 013

Opportunity Information: Apply for RFA DA 25 013

The NIH funding opportunity "Targeting Inflammasomes in HIV and Substance Use (R21 Clinical Trial Not Allowed)" (RFA-DA-25-013) supports early-stage, exploratory research aimed at clarifying how inflammasomes contribute to brain and nervous system damage linked to HIV infection and to acute or chronic exposure to drugs. The core scientific goal is to delineate the role of inflammasome-driven immune signaling in the neuropathology that can emerge when HIV-related processes and substance use intersect, including the ways these factors may amplify inflammation, immune activation, and downstream neuronal dysfunction. By focusing on inflammasomes, the announcement is centered on a specific set of innate immune pathways that can trigger inflammatory cascades and may help explain persistent neuroinflammation and immune dysregulation observed in some people with HIV, particularly in populations affected by substance use.

A major emphasis of the announcement is on understanding virus- and drug-induced immune activation in the central nervous system (CNS). Projects responsive to this call would typically investigate which inflammasome components and upstream triggers are engaged by HIV infection, by specific substances (or patterns of exposure), or by their combined effects. This includes efforts to identify molecular markers that reflect inflammasome activation and to map which CNS immune cells are involved, since pinpointing cell types and signatures associated with HIV-1 infection or disease progression could improve risk stratification and mechanistic understanding for substance-using populations. In practical terms, the opportunity encourages studies that move beyond broad inflammation measures and instead connect HIV and drug exposure to specific inflammasome mechanisms, cellular sources, and measurable biomarkers.

The opportunity also highlights a translational angle: identifying new therapeutic strategies that target inflammasome activation or suppression. While this is not a clinical trial mechanism, the intent is to generate the foundational evidence needed to support future intervention development, such as validating inflammasome-related targets, testing pathway modulation in preclinical or mechanistic experimental systems, and clarifying whether reducing maladaptive inflammasome activity could mitigate neuroinflammation or correct immune dysregulation driven by HIV and substance exposure. The overall public health rationale is that better mechanistic resolution could lead to more precise therapies for neurological complications and inflammatory consequences affecting people living with HIV who also experience substance use.

Mechanism details reflect an R21 exploratory/developmental grant, meaning the program is designed for high-impact, hypothesis-generating work, pilot studies, and early proof-of-concept research rather than large-scale confirmatory projects. The notice specifies "Clinical Trial Not Allowed," so applications should not propose clinical trials; instead, they should focus on mechanistic, observational, or preclinical/translational research that does not meet the definition of a clinical trial. The award ceiling listed is $275,000, and the original closing date provided is 2025-03-13. The program is issued by the National Institutes of Health and is associated with CFDA 93.279. The opportunity category is discretionary, and the funding instrument type is a grant.

Eligibility is broad and includes many types of U.S. organizations and some non-U.S. entities. Eligible applicants include state, county, city/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 and other tribal organizations; public housing authorities/Indian housing authorities; nonprofits with or without 501(c)(3) status; for-profit organizations other than small businesses; small businesses; and other eligible entities. The announcement explicitly calls out additional eligible applicants such as 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), faith-based or community-based organizations, eligible federal agencies, regional organizations, U.S. territories or possessions, and non-domestic (non-U.S.) entities (foreign organizations), as well as Indian/Native American tribal governments that are not federally recognized. This wide eligibility is meant to encourage participation from diverse institutional settings, including those closely connected to communities disproportionately affected by HIV and substance use.

• The National Institutes of Health in the education, health sector is offering a public funding opportunity titled "Targeting Inflammasomes in HIV and Substance Use (R21 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 2023-10-17.
• Applicants must submit their applications by 2025-03-13. (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 $275,000.00 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 25 013

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