Targeting Inflammasomes in Substance Abuse and HIV (R21 Clinical Trial Not Allowed) | RFA DA 24 004

Opportunity Information: Apply for RFA DA 24 004

Targeting Inflammasomes in Substance Abuse and HIV (R21 Clinical Trial Not Allowed) is a National Institutes of Health (NIH) discretionary grant opportunity (Funding Opportunity Number RFA-DA-24-004; CFDA 93.279) that supports early-stage, exploratory research on how inflammasomes contribute to brain and nervous system damage linked to drug exposure and HIV infection. The central focus is on clarifying the biological role of inflammasome pathways in the neuropathology that can arise from acute or chronic substance use, HIV-1 infection, or the combination of both. The announcement emphasizes the idea that drug use and HIV can each drive immune activation, and that inflammasomes may be a key mechanism connecting these exposures to neuroinflammation and broader immune dysregulation in the central nervous system (CNS).

The research goal is to improve understanding of virus- and drug-induced immune signaling in ways that can translate into practical scientific advances. Projects are expected to help identify molecular markers (for example, measurable molecules or pathway signatures) and specific CNS immune cell types associated with HIV-1 infection, disease progression, or neurological complications, particularly in populations affected by substance use. By mapping out which inflammasome components are activated, where they are activated in the CNS, and under what conditions, investigators can potentially define biomarkers that predict risk, track progression, or reveal treatment response in people with HIV who also use drugs.

A second major theme is therapy-oriented discovery, but within a non-clinical-trial framework. The announcement highlights interest in identifying or testing novel strategies to modulate inflammasome activity, including approaches that target activation or suppression of inflammasome pathways, with the broader aim of reducing neuroinflammation and correcting immune dysregulation. While this can include preclinical therapeutic exploration, mechanistic intervention studies, and proof-of-concept work, the funding opportunity explicitly states that clinical trials are not allowed under this announcement, meaning the supported studies should not involve prospective assignment of human participants to interventions to evaluate health-related outcomes.

The funding mechanism is the NIH R21, which is typically used for exploratory and developmental projects that can generate new directions, preliminary data, or innovative tools rather than large, long-term definitive studies. This makes the opportunity well suited for novel hypotheses about inflammasome function in HIV and substance use contexts, pilot studies establishing feasibility, or high-risk/high-reward experiments that may not yet be ready for larger R01-scale funding.

Eligibility is broad and includes many types of organizations that can contribute to biomedical and behavioral research. Eligible applicants listed include state, county, and local 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; other tribal organizations; public housing authorities/Indian housing authorities; nonprofits with or without 501(c)(3) status (other than institutions of higher education); for-profit organizations (other than small businesses); small businesses; and other organizations. The announcement also calls out additional eligible applicant categories 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; tribal governments that are not federally recognized; and non-domestic (non-U.S.) entities (foreign organizations). This breadth signals an intent to encourage participation from diverse institutions and communities, including those serving populations disproportionately affected by HIV and substance use.

Key administrative details provided include an original closing date of 2023-03-15 and a creation date of 2022-11-03. The listing does not specify an award ceiling or the expected number of awards in the provided source data, so applicants would typically confirm budget limits, project period details, and current status in the full NIH funding opportunity text and any associated notices. Overall, the opportunity is aimed at accelerating mechanistic and translationally relevant science on inflammasomes as a potential bridge between substance use, HIV-related immune activation, and CNS injury, with the longer-term goal of informing biomarkers and therapeutic strategies to address neuroinflammation and immune dysfunction in these overlapping conditions.

• The National Institutes of Health in the education, health sector is offering a public funding opportunity titled "Targeting Inflammasomes in Substance Abuse and HIV (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 2022-11-03.
• Applicants must submit their applications by 2023-03-15. (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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