The National Institutes of Health (NIH), through the National Institute of Allergy and Infectious Diseases (NIAID), is inviting applications for the **Targeting Cell Surface HIV Envelope for Cell Elimination (R01 Clinical Trial Not Allowed)** funding opportunity. This initiative aims to support research advancing our understanding of HIV-1 Envelope (Env) surface expression, mechanisms of biologic-mediated elimination of HIV-infected cells, and the development of novel immunotherapeutic strategies.

The program focuses on basic and translational research into HIV-1 Env biology to inform innovative approaches for eliminating HIV-infected cells, particularly those with low Env expression. Research should emphasize understanding Env surface expression, its regulation, and its interaction with host factors and engineered biologics. Potential projects could explore molecular pathways controlling Env expression, structural mechanisms of biologic-mediated cell killing, or strategies to enhance immune recognition of Env-expressing cells.

Eligible applicants include higher education institutions, non-profits, for-profit organizations, local and state governments, and foreign institutions. Individuals with the necessary skills and resources are encouraged to apply, regardless of background. Foreign components and collaborations are permitted. Applicants must ensure their organizations are registered in the **System for Award Management (SAM)** and eRA Commons.

Proposed studies must align with the specific goals of this NOFO. Applications investigating transcriptional regulation of Env, latency reversal agents, new broadly neutralizing antibodies, or high-throughput small molecule screens will be deemed non-responsive. Applications involving clinical trials are also excluded. Applicants should provide plans for using complementary approaches, validating findings in physiologically relevant models, and addressing challenges like low-level Env expression on infected cells.

Funding levels are not capped but must reflect project needs, with a maximum project period of five years. Applications requesting direct costs of $500,000 or more in any year must contact the Scientific/Research Contact six weeks before submission. All applications must comply with NIH policies on data sharing, inclusion, and rigor in experimental design.

Applications are due by **5:00 PM local time** on standard NIH AIDS funding cycles, starting May 7, 2025, and continuing until the expiration date of January 8, 2028. Reviews will consider the significance of the research, innovation, rigor of the approach, and the qualifications of the research team. Successful applicants will be notified via a Notice of Award, and all projects must comply with NIH and HHS policies.