Role of T-Cells in HIV CNS Reservoir Seeding, Persistence, and Neuropathogenesis (R21 Clinical Trial Not Allowed) | RFA MH 26 111

Opportunity Information: Apply for RFA MH 26 111

The National Institutes of Health (NIH), including the National Institute of Mental Health (NIMH), is soliciting applications for an R21 exploratory research grant focused on how T cells contribute to HIV infection in the central nervous system (CNS), specifically how HIV seeds reservoirs in the brain, how those reservoirs persist over time even during effective antiretroviral therapy (ART), and how immune activity in the CNS may drive ongoing neuroinflammation and neurological injury. The opportunity is framed around a major unresolved problem in HIV medicine: even when ART suppresses HIV to very low or undetectable levels in blood and achieves strong virologic control, many people still experience HIV-associated CNS comorbidities and subtle neurological impairments, suggesting that viral persistence and inflammatory processes in the brain can continue despite treatment. A central idea behind the funding announcement is that understanding the immunology of HIV in the CNS, especially the roles of different T-cell populations, is essential for advancing strategies aimed at either a sterilizing cure (eliminating all replication-competent virus) or a functional cure (long-term control without ongoing therapy), and for reducing the neurological complications that remain common in the ART era.

Scientifically, the grant highlights that HIV reaches the CNS early after infection and that multiple immune cell types participate in both viral entry into the brain and subsequent damage. CD4 T cells and monocytes are emphasized as key mediators of HIV entry into the CNS and as potential long-lived sources of viral persistence that can contribute to neuronal injury. At the same time, CD8 T cells are described as being heavily recruited into the CNS during acute infection, likely reflecting an attempt by the immune system to control local viral replication. The opportunity is therefore positioned to encourage studies that disentangle the protective versus pathogenic roles of these T-cell responses in the CNS environment, including how immune surveillance, inflammation, and cell trafficking across the blood-brain barrier might influence reservoir establishment, maintenance, and the downstream consequences for brain function. While the title centers on T cells, the description makes clear that the broader CNS immune ecosystem (including interactions with monocytes and inflammatory pathways) is part of the problem space, especially in the context of persistent neuroinflammation under ART.

From an administrative standpoint, this is a discretionary NIH grant using the R21 mechanism (typically meant for early-stage, high-impact, or proof-of-concept work) and it is explicitly labeled "Clinical Trial Not Allowed," meaning applicants should propose non-clinical-trial research approaches rather than interventional studies that prospectively assign human participants to receive an intervention. The funding opportunity is listed under Funding Opportunity Number RFA-MH-26-111, with a closing date of March 18, 2025, and it is associated with CFDA numbers 93.242, 93.279, and 93.853. The activity areas fall under health and education-related research support, consistent with NIH biomedical research priorities.

Eligibility is broad and includes many types of domestic organizations such as state, county, city/township, and special district governments; public and state-controlled institutions of higher education; private institutions of higher education; independent school districts; and public housing authorities/Indian housing authorities. It also includes federally recognized Native American tribal governments and other Native American tribal organizations, as well as nonprofit organizations with or without 501(c)(3) status (excluding institutions of higher education in those nonprofit categories), for-profit organizations other than small businesses, and small businesses. The announcement also calls out additional eligible applicants and organization types of particular interest or inclusion, including Historically Black Colleges and Universities (HBCUs), Hispanic-serving Institutions, Tribally Controlled Colleges and Universities (TCCUs), Alaska Native and Native Hawaiian Serving Institutions, Asian American Native American Pacific Islander Serving Institutions (AANAPISISs), faith-based or community-based organizations, non-domestic (non-U.S.) entities/foreign organizations, regional organizations, Indian/Native American tribal governments that are not federally recognized, and U.S. territories or possessions. Overall, the opportunity is aimed at expanding and accelerating research that clarifies how T-cell biology intersects with HIV persistence in the brain and with ongoing CNS injury in treated infection, with the longer-term goal of informing cure strategies and reducing HIV-associated neurological complications.

• The National Institutes of Health in the education, health sector is offering a public funding opportunity titled "Role of T-Cells in HIV CNS Reservoir Seeding, Persistence, and Neuropathogenesis (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): 93.242, 93.279, 93.853.
• This funding opportunity was created on 2024-11-21.
• Applicants must submit their applications by 2025-03-18. (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.

Apply for RFA MH 26 111

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