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

The National Institutes of Health (NIH), through the National Institute of Allergy and Infectious Diseases (NIAID), has issued a Notice of Funding Opportunity (NOFO) titled "Elucidating Immunometabolic Responses to HIV Infection that Increase TB or HBV Risk (R21 Clinical Trial Not Allowed)." This opportunity supports innovative, exploratory, and developmental research (R21 mechanism) aimed at understanding how HIV-induced immunometabolic changes affect susceptibility to tuberculosis (TB) and hepatitis B virus (HBV), even in individuals successfully treated with combination antiretroviral therapy (cART). The initiative encourages the integration of multi-disciplinary expertise, novel analytical approaches such as artificial intelligence, and the utilization of existing clinical samples. This grant targets a critical knowledge gap in how HIV-associated immunometabolic remodeling affects immune regulation and response to co-infections. Individuals living with HIV (PLWH) are disproportionately affected by TB and HBV. TB remains the leading cause of death among PLWH, who are 18 times more likely to develop active TB. Furthermore, approximately 8% of PLWH are co-infected with HBV, increasing their risk of developing severe liver complications. Despite the use of cART, these risks persist, and the underlying mechanisms remain poorly understood. The grant aims to elucidate these mechanisms through basic, preclinical, and translational laboratory research, excluding clinical trials. Research proposals must be hypothesis-driven and focus specifically on how HIV-induced immunometabolic changes influence immune cell regulation, cell-cell interactions, treatment response, and progression of TB or HBV. Topics of interest include biomarker discovery, disease progression correlates, immune-metabolic pathway dissection, and identification of targets for host-directed therapies. Applications that study immunometabolism without the context of HIV or those exploring HIV effects without co-infection are not considered responsive. The funding encourages interdisciplinary collaboration and supports research using in vitro or in vivo model systems. Applicants must adhere to NIH submission protocols, including the use of the NIH ASSIST system or other approved submission platforms like Grants.gov Workspace. Applications must comply with the Research (R) Instructions from the NIH Application Guide. Required components include a biosketch with evidence of leadership in multidisciplinary teams, specific aims, research strategy, resource sharing plans, and a data management and sharing plan. The use of existing human samples is encouraged, but proper documentation and support letters must be included. The funding provides a maximum of $275,000 in direct costs over a two-year period, with no more than $200,000 allocated in any single year. No cost sharing or matching funds are required. The program does not allow for clinical trials. Applicants may submit new or resubmission applications, but overlapping submissions or submissions under appeal are not permitted. The eligibility extends to a broad range of entities including higher education institutions, nonprofits, for-profit organizations, governments, and foreign entities. The first submission date is April 7, 2025, with subsequent AIDS-related deadlines on May 7, 2025, and quarterly through January 2028. The funding opportunity expires on May 8, 2026. Key contacts include Dr. Josh Radke for scientific questions and Robert Kirker for financial matters. Applications will be reviewed based on significance, innovation, feasibility, and the applicant’s expertise and available resources. Awards are subject to NIH policies and federal regulations including data sharing, cybersecurity, and non-discrimination.

Use novel conceptual approaches and machine learning; ensure co-infection (HIV with TB or HBV) is addressed; avoid non-HIV or non-co-infection topics