Targeting Inflammasomes in HIV and Substance Use (R21 Clinical Trial Not Allowed) | RFA DA 25 068

Opportunity Information: Apply for RFA DA 25 068

The Targeting Inflammasomes in HIV and Substance Use funding opportunity (RFA-DA-25-068) is a National Institutes of Health (NIH) R21 grant mechanism focused on early-stage, exploratory research that clarifies how inflammasomes contribute to brain and nervous system damage (neuropathology) in the context of HIV infection and acute or chronic exposure to drugs of abuse. The central goal is to push the field toward a clearer mechanistic understanding of how virus- and drug-driven immune activation in the central nervous system (CNS) is regulated by inflammasome pathways, and how those pathways might be leveraged to improve outcomes for people living with HIV, especially within populations affected by substance use.

Scientifically, the opportunity is aimed at studies that delineate the role of inflammasomes in neuroinflammation and immune dysregulation linked to HIV and drug exposure. In practical terms, this means supporting projects that can identify which inflammasome-related molecular markers and which CNS immune cell types are associated with HIV-1 infection, disease progression, or HIV-related neurological complications when substance use is also present. A major emphasis is on immune activation as a shared and potentially synergistic driver of harm: HIV can trigger chronic inflammation, and many substances can also alter innate immune signaling and neuroimmune responses. By teasing apart where these processes overlap or amplify each other, the research supported under this announcement is intended to reveal actionable targets for intervention.

A key translational thread in the announcement is the search for new therapeutic strategies that either inhibit excessive inflammasome activation or, where relevant, modulate/suppress inflammasome signaling to reduce neuroinflammation and downstream immune dysfunction. The expectation is not necessarily to run clinical intervention studies, but rather to generate the foundational evidence needed to justify future therapeutic development. Because this is an R21 and explicitly “Clinical Trial Not Allowed,” the supported work should remain in the preclinical, mechanistic, or observational space rather than testing interventions in human participants as clinical trials. Applicants would typically use the R21 structure to propose innovative approaches, pilot datasets, proof-of-concept experiments, or new models that can later mature into larger R01-scale programs.

From an administrative standpoint, this is a discretionary grant with an activity area spanning education and health, and it is associated with CFDA number 93.279. The opportunity lists an award ceiling of $500,000. The original application closing date is March 13, 2025, and the funding announcement was created on October 29, 2024. While the notice references expected awards, the provided source data does not specify a number.

Eligibility is broad and includes many common applicant types across government, academia, nonprofit, and industry. 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; tribal organizations that are not federally recognized; public housing authorities and Indian housing authorities; nonprofits with or without 501(c)(3) status (other than institutions of higher education); for-profit organizations (other than small businesses); and small businesses. In addition, the announcement explicitly highlights a wide range of “other eligible applicants,” 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), faith-based or community-based organizations, eligible federal agencies, regional organizations, U.S. territories or possessions, and non-U.S. entities (foreign organizations). This broad eligibility is consistent with the goal of encouraging diverse scientific and community perspectives on HIV, substance use, and neuroimmune biology.

Overall, the grant is designed to accelerate discovery at the intersection of HIV neuropathogenesis, substance use biology, and innate immune signaling by focusing attention on inflammasomes as a potentially unifying mechanistic pathway. By supporting studies that identify relevant CNS immune cells, molecular markers, and drug- and virus-induced immune activation signatures, the announcement aims to set up future advances in biomarker development and targeted anti-inflammatory or immune-modulating therapeutic approaches for neuroinflammation and immune dysregulation in people 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 2024-10-29.
• 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 $500,000.00 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 25 068

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