Interplay of Autophagy Regulated Cell Death and HIV Pathogenesis in Substance Use Disorders (R21 Clinical Trial Not Allowed) | RFA DA 25 010

Opportunity Information: Apply for RFA DA 25 010

The Interplay of Autophagy Regulated Cell Death and HIV Pathogenesis in Substance Use Disorders funding opportunity (RFA-DA-25-010) is a National Institutes of Health (NIH) discretionary grant competition using the R21 mechanism, and it is explicitly not open to clinical trials. The scientific goal is to support exploratory, early-stage research that connects three intersecting areas: (1) autophagy-regulated pathways that can influence cell survival and cell death, (2) HIV pathogenesis, and (3) the way acute and chronic substance use shapes these processes, particularly in the central nervous system (CNS). The NOFO is centered on how drug exposure may change CNS cellular immune responses in the context of HIV, with the expectation that applicants will investigate mechanistic links rather than run interventional studies in human participants.

A key emphasis is on the CNS and cellular immunology, meaning the work is meant to dig into how immune-related cells in or interacting with the brain and spinal cord respond under combined pressures of HIV and substances of misuse, and how autophagy-related cell death programs might help explain observed outcomes. Autophagy is a fundamental cellular process involved in recycling damaged components and maintaining cellular homeostasis, and it can intersect with inflammatory signaling and regulated cell death pathways. In HIV infection, and especially in the CNS where persistent inflammation and immune activation can contribute to neurologic complications, shifts in autophagy and cell death regulation may influence viral persistence, neuroinflammation, and tissue injury. This NOFO is aimed at studies that clarify those relationships when drug exposure is layered on top, recognizing that different substances and patterns of use (acute versus chronic) can have distinct effects on immune signaling, stress responses, and cellular metabolism.

Because this is an R21 opportunity, it is typically suited for innovative, higher-risk projects that generate strong proof-of-concept data, new mechanistic insights, or enabling datasets that can support later, more expansive research. The activity category is listed under education and health, and the CFDA number associated with the opportunity is 93.279. The award ceiling is stated as $275,000, signaling a relatively modest budget consistent with exploratory projects rather than large, multi-site programs. The opportunity was created on 2023-12-06, and the original closing date is 2024-11-14.

Eligibility is broad and includes many types of U.S. domestic organizations and certain non-U.S. entities. 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 that are not federally recognized tribal governments; public housing authorities/Indian housing authorities; nonprofit organizations with and without 501(c)(3) status (when they are not institutions of higher education); for-profit organizations other than small businesses; small businesses; and other eligible entities. The NOFO also highlights additional eligible applicant groups 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; U.S. territories or possessions; regional organizations; and non-domestic (non-U.S.) entities (foreign organizations). This wide eligibility reflects an intent to encourage participation from a diverse range of research environments, including institutions and organizations that serve underrepresented communities or operate in unique regional contexts.

In practical terms, a competitive application would be expected to propose clear, testable research questions about how substance use alters autophagy-related mechanisms and regulated cell death in CNS-relevant immune or neural cell types during HIV infection, and how those molecular and cellular effects relate to HIV-associated pathology. Since clinical trials are not allowed, the work would generally be positioned around preclinical models, in vitro systems, ex vivo analyses, computational or systems biology approaches, or other mechanistic strategies that do not constitute a clinical trial. The overarching intent is to produce actionable biological insight into HIV neuropathogenesis in the setting of substance use disorders, with autophagy-regulated cell death as the conceptual and mechanistic bridge.

• 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 (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 2023-12-06.
• 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.)
• 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 25 010

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