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

The Department of Health and Human Services, through the National Institutes of Health and its component, the National Institute of Allergy and Infectious Diseases, has released a new funding opportunity titled Elucidating Immunometabolic Responses to HIV Infection that Increase TB or HBV Risk under the R21 Exploratory/Developmental Research Grant mechanism. This opportunity, announced under funding opportunity number PAR-25-316, was updated on March 31, 2025, to align with current agency priorities and encourages applicants to carefully reread the full announcement before submitting applications. The purpose of this funding opportunity is to support research focused on understanding how HIV-induced immunometabolic changes in individuals suppressed on combination antiretroviral therapy affect immune responses and increase the risk of poor outcomes from co-infections with Mycobacterium tuberculosis or hepatitis B virus. While antiretroviral therapy controls viral replication, people living with HIV remain at significantly higher risk for TB and HBV-related disease progression. This program aims to investigate how alterations in immunometabolism impact immune regulation, treatment responses, and co-infection disease outcomes. Research may ultimately identify biomarkers of disease progression or therapeutic targets to reduce TB and HBV risks in people living with HIV. This program will support hypothesis-driven basic, preclinical, and translational research that examines immunometabolic pathways and their influence on TB and HBV disease. Eligible research topics include studying metabolic alterations caused by HIV infection, exploring their role in immune cell interactions, performing multi-omic immune cell analyses, and identifying novel therapeutic targets or biomarkers. Proposals must remain directly relevant to HIV-driven immunometabolic changes and their link to TB or HBV risk. Applications that investigate unrelated immunometabolic mechanisms, HIV alone without co-infection, or clinical trials will not be reviewed under this program. The companion funding opportunity PAR-25-315 supports R01-level projects for more advanced studies. The R21 mechanism allows for exploratory and developmental projects with budgets not exceeding $275,000 in direct costs over two years, with a limit of $200,000 in any single year. Awards are contingent on NIH appropriations and the number of meritorious applications received. Project periods may not exceed two years. NIH policies, including those related to data management, genomic data sharing, and human subjects protections, apply to all awards. Clinical trials are not permitted under this announcement. Eligibility is broad and includes higher education institutions, nonprofits, for-profit organizations including small businesses, state, county, and municipal governments, tribal governments and organizations, public housing authorities, school districts, faith-based and community organizations, and foreign entities. Individuals with the necessary expertise may apply as program directors or principal investigators. Multiple applications are permitted if they are scientifically distinct. Cost sharing is not required. All applicant organizations must complete registrations with SAM, Grants.gov, and eRA Commons before submission. Applications must be submitted electronically via NIH ASSIST, Grants.gov Workspace, or an institutional system-to-system solution. The open date for submission is April 7, 2025. The first application due date for AIDS-related research is May 7, 2025, with subsequent standard NIH due dates including September 7, 2025, January 7, 2026, and continuing on a recurring basis through January 7, 2028. All applications are due by 5:00 p.m. local time of the applicant organization. The expiration date for this opportunity is January 8, 2028. Review will be conducted by NIH peer review groups with evaluation criteria focusing on significance, innovation, approach, feasibility, investigator expertise, and institutional resources. For scientific and research questions, applicants may contact Josh Radke, Ph.D., at josh.radke@nih.gov or by phone at 301-761-6525. For grants management inquiries, the contact is Robert Kirker at robert.kirker2@nih.gov or 301-451-3176. General questions about application instructions can be directed to GrantsInfo@nih.gov, and submission issues can be addressed by the eRA Service Desk or Grants.gov Customer Support. Successful applicants will receive a Notice of Award from NIH outlining award terms and conditions.