Mitochondrial-associated Mechanisms of Neuropathological and Immunodeficient Aging in the Context of HIV and SUD (R21 Clinical Trials Not Allowed) | RFA DA 26 010

Opportunity Information: Apply for RFA DA 26 010

The National Institutes of Health (NIH) is soliciting applications for a discretionary research grant opportunity titled "Mitochondrial-associated Mechanisms of Neuropathological and Immunodeficient Aging in the Context of HIV and SUD (R21 Clinical Trials Not Allowed)," under Funding Opportunity Number RFA-DA-26-010 (CFDA 93.279). This call focuses on early-stage, exploratory research (R21 mechanism) aimed at understanding how mitochondrial function intersects with aging-related changes in the brain and immune system among people living with HIV, particularly when there is also exposure to addictive substances or substance use disorder (SUD). Clinical trials are not allowed under this opportunity, so proposed studies should be preclinical, mechanistic, observational, or otherwise non-trial in nature rather than testing clinical interventions in human participants.

The core goal is to drive research into both protective and harmful (pathogenic) biological mechanisms that sit at the crossroads of mitochondrial biology, HIV infection, aging processes, and substance exposure. Mitochondria are central to cellular energy production and are also deeply involved in oxidative stress, inflammation, metabolic regulation, and programmed cell death, all of which can influence neurodegeneration and immune decline as people age. In the context of HIV, long-term infection and treatment can be associated with chronic immune activation and accelerated aging phenotypes, and many substances of abuse can further disrupt mitochondrial function, amplify neuroinflammation, and worsen systemic health. The intent here is to generate foundational mechanistic knowledge that can later be translated into more targeted therapies or prevention strategies, ultimately improving health outcomes for individuals aging with HIV who also experience substance use or addiction.

Because the activity category is listed under education and health, and the administering agency is NIH, applicants should expect the typical NIH emphasis on strong scientific rationale, rigorous study design, and clear significance to public health. While the public summary highlights neuropathological and immunodeficient aging, the scope implied by the title and description supports a wide range of mechanistic angles, such as how mitochondrial dysfunction contributes to neurocognitive impairment, neurodegenerative-like changes, immune senescence, inflammatory signaling, or increased vulnerability to comorbidities in aging populations affected by HIV and substance exposure. The opportunity is positioned as a stepping-stone for new directions or high-impact hypotheses that may not yet have extensive preliminary data, which is consistent with the R21 exploratory approach.

Eligibility is broad and includes many types of domestic organizations: 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; non-federally recognized Native American tribal organizations; public housing and Indian housing authorities; nonprofits with or without 501(c)(3) status (excluding institutions of higher education in those specific nonprofit categories); for-profit organizations (other than small businesses); and small businesses. The announcement also explicitly 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, regional organizations, U.S. territories or possessions, and non-domestic (non-U.S.) entities (foreign organizations). In practice, that means the program is open not only to traditional research universities and medical centers, but also to a wide range of institutions that serve underrepresented communities and organizations positioned to contribute specialized expertise, unique populations, or distinctive research infrastructure.

Key administrative details provided include an original closing date of March 10, 2026, and a creation date of September 30, 2024. The funding instrument type is a grant, and the award ceiling and expected number of awards are not specified in the provided source data, which typically means applicants should consult the full announcement text for budget guidance and any institute-specific limits. Overall, the opportunity is best understood as a focused NIH research call encouraging innovative, mechanistic work on mitochondrial drivers of brain and immune aging in HIV, with explicit attention to the complicating and clinically important role of substance use and addiction, and with the longer-term aim of enabling more precise, biology-informed interventions in the future.

• The National Institutes of Health in the education, health sector is offering a public funding opportunity titled "Mitochondrial-associated Mechanisms of Neuropathological and Immunodeficient Aging in the Context of HIV and SUD (R21 Clinical Trials 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 2024-09-30.
• Applicants must submit their applications by 2026-03-10. (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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