Elucidating Immunometabolic Responses to HIV Infection that Increase TB or HBV Risk (R21 Clinical Trial Not Allowed)

The National Institutes of Health (NIH), under the U.S. Department of Health and Human Services, is a major federal agency dedicated to medical research. Within NIH, the National Institute of Allergy and Infectious Diseases (NIAID) is leading efforts to address infectious, immunologic, and allergic diseases through funding and research initiatives. This grant opportunity, titled “Elucidating Immunometabolic Responses to HIV Infection that Increase TB or HBV Risk (R21 Clinical Trial Not Allowed),” is part of NIAID's strategic focus on understanding complex interactions between chronic infections and immune system function, particularly in the context of HIV co-infection with tuberculosis (TB) or hepatitis B virus (HBV). This funding opportunity supports exploratory and developmental research aiming to define how HIV-induced changes to immunometabolism influence susceptibility to secondary infections like TB and HBV. Despite suppression of HIV with combination antiretroviral therapy (cART), people living with HIV (PLWH) remain at heightened risk for TB and HBV-related complications. The NOFO emphasizes research into how altered immune cell metabolism and function—driven by chronic HIV infection—affects disease progression, immune regulation, cell signaling, and treatment responses when co-infected with TB or HBV. The goal is to identify new therapeutic targets or biomarkers that can mitigate these risks and guide host-directed treatment strategies. The grant encourages multidisciplinary approaches that combine immunology, systems biology, and infectious disease research. Use of novel technologies such as machine learning or artificial intelligence (AI) and integration of multi-omic datasets are highly encouraged. Projects may also utilize existing clinical samples and models. Applications may not propose clinical trials or focus solely on HIV or other non-HIV-driven immunometabolic processes. Research must be exploratory, consistent with the R21 mechanism, and conceptual in nature, potentially setting the stage for future R01 studies. Applicants must adhere to NIH’s comprehensive application guidance and submission must be made via NIH ASSIST, Grants.gov Workspace, or institutional S2S systems. Components include the Research Strategy, Specific Aims, and required biosketches demonstrating leadership experience in multidisciplinary research. The award supports up to $275,000 in direct costs over two years, with a maximum of $200,000 in any single year. The project period is limited to two years, aligning with R21 standards. Resubmissions are allowed, but clinical trials are not permitted under this opportunity. Eligibility is broad and inclusive, covering U.S.-based public and private higher education institutions, nonprofits, small businesses, local and tribal governments, and foreign organizations. All applicants must complete required registrations with SAM.gov, eRA Commons, and Grants.gov. NIH encourages applications from interdisciplinary teams with a diverse range of scientific expertise. Applications are subject to NIH’s rigorous peer review process, which considers significance, innovation, approach, investigator expertise, and environment. This NOFO originally opened for applications on April 7, 2025, with a final expiration date set for February 18, 2026, per NOT-AI-26-009. While currently expired, applications may still be accepted on a limited basis under NIH’s late submission and continuous submission policies. Standard AIDS due dates were applicable, including cycles in May and September through 2027. In total, the opportunity recurs on a standard cycle and prospective applicants should monitor the NIH Guide for Notices of Funding Opportunities for reissuance or related programs. Key contacts include Josh Radke, Ph.D. for scientific questions ([email protected], 301-761-6525) and Robert Kirker for financial questions ([email protected], 301-451-3176).