The Role of T-Cells in HIV CNS Reservoir Seeding, Persistence, and Neuropathogenesis (R01 Clinical Trial Not Allowed) funding opportunity, issued by the National Institutes of Health (NIH), seeks to support research that examines the mechanisms and roles of T-cells in the central nervous system (CNS) in the context of HIV. The primary goals include understanding T-cell involvement in CNS reservoir seeding, persistence of HIV, and related neuropathogenesis. The initiative also encourages developing therapeutic approaches to address T-cell neuro-invasion, reservoir maintenance, and neuropathogenesis to contribute to an HIV cure and address CNS dysfunctions associated with HIV.

Research under this program may focus on topics such as the mechanisms by which HIV-infected T-cells infiltrate the CNS, T-cell-mediated blood-brain barrier transmigration, and their contribution to CNS viral reservoirs. Investigators are encouraged to explore the role of T-cells in neuroinflammation, interactions with myeloid cells, and their potential contribution to neuropathogenesis even under antiretroviral therapy. The program also promotes the use of innovative methodologies, such as advanced CNS cell systems, single-cell technologies, animal models, and human clinical samples. Studies on therapeutic strategies targeting T-cells to mitigate their role in neuropathogenesis and reservoir persistence are particularly encouraged.

Funding is provided by multiple NIH components. NIMH intends to allocate $2,000,000 in fiscal year 2026 to fund 3-5 awards, while NIDA and NINDS will commit $2,000,000 and $1,500,000, respectively, to support additional awards. Future funding is subject to annual appropriations. There are no limitations on budget requests, but costs must reflect the actual needs of the project. The maximum project period is five years. Applications that fail to address T-cell roles in the CNS or focus solely on myeloid cells or peripheral systems will be deemed non-responsive.

Eligible applicants include public and private institutions of higher education, nonprofit organizations, for-profit entities, state and local governments, foreign organizations, and others. Applicants must register in advance with System for Award Management (SAM), eRA Commons, and Grants.gov. Letters of intent are due by February 18, 2025, and final applications must be submitted by March 18, 2025.

Applications must adhere to the NIH’s rigorous guidelines and submission requirements. Research strategies should outline the significance and innovation of the work, provide clear plans for data management and sharing, and include the use of NIH Common Data Elements for human subjects research. The NIMH Data Archive will serve as the repository for shared data. Review criteria include scientific significance, methodological rigor, feasibility, and the expertise of the research team. Applications will undergo peer review, and those with the highest scientific merit will advance for funding consideration.

Applicants are encouraged to consult with NIH program officials for guidance. Additional details, including submission instructions and review procedures, are available in the full Notice of Funding Opportunity.