Elucidating Immunometabolic Responses to HIV Infection that Increase TB or HBV Risk (R01 Clinical Trial Not Allowed)

The U.S. Department of Health and Human Services, through the National Institutes of Health and its National Institute of Allergy and Infectious Diseases, has released a funding opportunity titled Elucidating Immunometabolic Responses to HIV Infection that Increase TB or HBV Risk (R01 Clinical Trial Not Allowed). This initiative, announced under PAR-25-315, is designed to support investigator-led research that examines how HIV-induced immunometabolic alterations in individuals suppressed on combination antiretroviral therapy influence immune responses and increase vulnerability to secondary infections such as tuberculosis and hepatitis B virus. The notice emphasizes the importance of understanding mechanisms of immunometabolic regulation and their implications for disease progression, biomarkers, and potential host-directed therapies. The program builds upon established findings that people living with HIV face significantly higher risks of developing TB and HBV-related complications despite viral suppression under antiretroviral therapy. This funding opportunity seeks to fill critical gaps in knowledge regarding why these risks persist and how immunometabolism may be leveraged to address them. Applications are expected to integrate multi-omic analyses, immune system modeling, and potentially advanced computational approaches such as artificial intelligence and machine learning to identify key mechanisms and therapeutic targets. Nonresponsive applications would include those that do not address HIV-related immunometabolism or that propose clinical trials. Eligible applicants include a broad range of organizations: higher education institutions, nonprofits, for-profit organizations including small businesses, state and local governments, tribal governments and organizations, faith-based and community-based organizations, and foreign institutions. Individuals with the necessary expertise are also eligible to serve as principal investigators. Applications may be submitted by single or multiple principal investigators, and foreign components are allowed. There is no cost-sharing requirement for this program, and applicants may submit more than one distinct application. All applicants must complete federal registration processes including SAM.gov, Grants.gov, and eRA Commons prior to submission. Applications are to be submitted electronically through NIH ASSIST, institutional system-to-system solutions, or Grants.gov Workspace, with tracking and confirmation via eRA Commons. Standard NIH R01 policies apply, including requirements for biosketches, resource sharing plans, data management and sharing plans, and human subjects or vertebrate animal protections where applicable. Applicants requesting $500,000 or more in direct costs must contact NIH program staff in advance. Compliance with the NIH Grants Policy Statement is required, and incomplete or nonresponsive applications will not be reviewed. Review will follow NIH’s peer review system, with evaluation criteria focused on significance, innovation, approach, investigator qualifications, and institutional environment. Specific emphasis will be placed on projects that advance understanding of biological mechanisms underlying HIV-induced immunometabolic alterations that influence immune regulation and risk of TB or HBV progression. Additional review criteria address rigor, feasibility, and the incorporation of multidisciplinary and computational strategies where appropriate. Key dates for this funding opportunity include an open date of April 7, 2025, and multiple application due dates for AIDS-related applications: May 7, 2025; September 7, 2025; January 7, 2026; and recurring thereafter through January 7, 2028. Applications must be submitted by 5:00 PM local time of the applicant organization. The earliest anticipated start date for successful awards will vary by cycle, beginning in December 2025. The funding opportunity will expire on January 8, 2028. Scientific inquiries may be directed to Dr. Josh Radke, National Institute of Allergy and Infectious Diseases, at josh.radke@nih.gov or 301-761-6525. Grants management questions should be directed to Robert Kirker at robert.kirker2@nih.gov or 301-451-3176.