The Role of T-Cells in HIV CNS Reservoir Seeding, Persistence, and Neuropathogenesis (R21) grant opportunity aims to support exploratory research that advances understanding of T-cell mechanisms in HIV-associated central nervous system (CNS) reservoir seeding, persistence, and neuropathogenesis. This funding opportunity is targeted at high-risk, high-reward projects that lack extensive preliminary data but have the potential to significantly enhance the field. The research may involve state-of-the-art tools such as single-cell technologies, CNS cell systems, and animal or organoid models to investigate T-cell interactions and their implications for HIV treatment and remission. Collaborative, multidisciplinary research is encouraged but not mandatory.

The grant addresses gaps in understanding the contribution of T-cells to HIV CNS infection and related complications despite antiretroviral therapy (ART). It seeks to identify mechanisms by which T-cells contribute to neuroinflammation, neurodegeneration, and blood-brain barrier dysfunction, while also exploring therapeutic strategies to target T-cell neuroinvasion and reservoir maintenance. Key areas of interest include the role of T-cell subsets, interactions with myeloid cells, and the potential for CNS-derived infected T-cells to reseed peripheral reservoirs.

Eligible applicants include domestic and foreign higher education institutions, nonprofits, for-profit organizations, and governments. This opportunity supports new R21 applications and is limited to projects without clinical trials. Applicants may request up to $275,000 in direct costs over a two-year period, with a maximum of $200,000 allowed in a single year. The earliest submission date is February 17, 2025, with the application deadline on March 18, 2025.

Applications must adhere strictly to NIH requirements, including specific submission formats, guidelines, and data-sharing policies. Each submission should include a comprehensive research strategy that emphasizes the significance, innovation, and approach of the proposed study. Plans for data management and sharing, particularly via the National Institute of Mental Health Data Archive, are required.

Proposals will be reviewed based on their scientific merit, with emphasis on innovation, significance, rigor, and feasibility. Evaluation will include the project’s potential to enhance understanding of T-cell mechanisms in HIV-related CNS conditions and its alignment with program priorities. The research environment and investigator expertise will also be considered.

Successful applicants will receive Notices of Award by December 2025. Post-award responsibilities include compliance with federal and NIH-specific policies, such as data-sharing requirements and safety monitoring for human and animal subjects. For detailed inquiries, applicants are encouraged to contact the listed program and review officers.