Role of Defective Proviruses in HIV Persistence (R01 Clinical Trial Not Allowed)

The "Role of Defective Proviruses in HIV Persistence (R01 Clinical Trial Not Allowed)" grant, issued by the National Institutes of Health (NIH), specifically engages several NIH components including the National Institute of Allergy and Infectious Diseases (NIAID), National Institute of Mental Health (NIMH), National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), and the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD). The grant aligns with the NIH’s overarching mission to advance knowledge and support biomedical research. The specific aim of this opportunity is to deepen understanding of defective HIV proviruses and their roles in HIV pathogenesis, immune system interactions, and impacts on cure strategies and clinical assay development. This funding opportunity arises from growing evidence that defective proviruses—non-functional viral DNA sequences integrated into host genomes—remain persistent despite long-term antiretroviral therapy (ART) and may express viral RNAs and proteins with clinical consequences. Researchers are encouraged to explore the biological impact of these defective proviruses in individuals undergoing ART, particularly their role in chronic immune activation, comorbidity development, immune exhaustion, and interference with HIV cure strategies such as therapeutic broadly neutralizing antibodies (bNAbs). The funding scope permits a range of activities including basic and translational research, assay development, and the use of longitudinal clinical or preclinical human samples. Notably, clinical trials are not allowed under this opportunity, but projects must include analysis of human samples. Applicants may also conduct studies related to assay optimization that aim to improve specificity by excluding defective proviruses from measurements relevant to viral load, drug resistance, and bNAb sensitivity. Projects may focus on various anatomical and demographic populations of interest to the participating institutes—e.g., gut, liver, CNS, or pediatric and perinatal populations. Applications are accepted under the R01 Research Project Grant mechanism, and budgets are not expected to exceed $500,000 in direct costs per year for up to five years. There is no cost-sharing requirement. Submission windows follow the NIH standard AIDS cycle due dates: May 7, September 7, and January 7 of each applicable year through January 2028. The next deadline is May 7, 2026. Applications must be submitted electronically through one of the NIH-approved portals (ASSIST, institutional system-to-system, or Grants.gov Workspace) and comply with NIH policies including data sharing and human subjects protections. Eligible applicants include a broad array of domestic and foreign organizations, including public and private institutions of higher education, nonprofit and for-profit organizations, governments at various levels, Native American tribal entities, and other specialized public bodies. Foreign components are allowed. Applicants must complete required registrations in systems such as SAM.gov, eRA Commons, and Grants.gov. Review criteria emphasize the importance of the proposed research, scientific rigor and feasibility, and qualifications of the research team and environment. Scientific contacts are designated for each participating institute to guide applicants based on alignment with specific mission areas. These include Dr. Leia Novak (NIAID), Dr. Jeymohan Joseph (NIMH), Dr. Eric Lorenzo (NICHD), and Dr. Khoa Nguyen (NIDDK). Administrative inquiries can be directed to listed grants management officers. The opportunity expires May 8, 2026, and is supported under the assistance listings 93.855, 93.865, 93.847, and 93.242.

Provide clear methodological distinctions between provirus types; demonstrate access to human samples; emphasize assay optimization to exclude defective provirus from clinical metrics.