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

The National Institute on Drug Abuse (NIDA) is inviting applications for the R21 Exploratory/Developmental Research Grant titled “Mitochondrial-associated Mechanisms of Neuropathological and Immunodeficient Aging in the Context of HIV and Substance Use Disorders (SUD).” This funding opportunity seeks to support early-stage research examining how mitochondrial dysfunction may contribute to aging processes, particularly in individuals with HIV who also use addictive substances. Specifically, the grant aims to deepen understanding of both pathogenic and protective mitochondrial mechanisms that may affect neurocognitive and immunological aging, ultimately guiding potential therapies for those aging with HIV and SUD. The funding emphasizes research on mitochondrial stress, gene expression, oxidative damage, and how these processes may accelerate aging in the context of HIV, antiretroviral therapy (ART), and various addictive substances, including opioids, nicotine, methamphetamine, cannabinoids, and stimulants. This NOFO encourages a focus on mitochondrial dynamics in both neural and immune cells to determine how mitochondrial damage may maintain viral reservoirs, contribute to neurodegenerative changes, or impact immune senescence. Relevant research areas include studies on mitochondrial haplotypes, stress responses, DNA mutations, and how specific substances impact mitochondrial pathways associated with age-related neuropathology and immune deficits. Applicants must propose a Plan for Enhancing Diverse Perspectives (PEDP), detailing strategies for including diverse viewpoints and participants in the research process. The PEDP will be reviewed as part of the application’s scientific merit, requiring actionable steps for inclusivity. The proposed research must be basic or preclinical and should not involve clinical trials. Applications not focusing on the intersection of HIV and SUD, or those involving only alcohol as the substance of interest, are not eligible for consideration. The grant provides an anticipated budget of $3 million across Fiscal Year 2026 to fund 3-6 projects under this NOFO and its companion R01 mechanism. Each R21 project may request up to $275,000 in direct costs over a two-year period, with no more than $200,000 allowable in any single year. The maximum project period is two years. Eligible applicants include U.S.-based and foreign public or private institutions of higher education, for-profit and nonprofit organizations, as well as various levels of government and community-based organizations. Foreign organizations are eligible to apply, and U.S.-based institutions may include foreign components if relevant to the research. Application requirements are extensive, including mandatory registrations in SAM, Grants.gov, and eRA Commons. Each principal investigator (PI) must obtain an eRA Commons ID. Applications must comply strictly with the NIH’s updated application instructions (FORMS-I) and must be submitted electronically by the posted deadlines, which include an optional letter of intent due by February 10, 2025, and the full application due by March 10, 2025, at 5:00 PM local time. Applications will be reviewed based on significance, innovation, approach, feasibility, and the qualifications of the investigative team. Reviewers will specifically evaluate the quality of the proposed PEDP, approach to data management and sharing, and whether the research plan is rigorous and likely to yield reproducible, unbiased findings. Scored criteria include the importance of the research in addressing significant knowledge gaps, innovation, and overall project feasibility. The earliest anticipated start date for awarded projects is December 2025, following the scientific merit review and approval by the NIH Advisory Council. Applicants are encouraged to consult NIDA program officials listed in the NOFO for specific guidance and to ensure alignment with NOFO objectives before developing their applications.