Impact of Immunotherapies on CNS Outcomes in People with HIV: Potential Benefits, Challenges and Risks

The National Institute of Mental Health (NIMH), part of the U.S. Department of Health and Human Services, plans to release a Notice of Funding Opportunity (NOFO) titled “Impact of Immunotherapies on CNS Outcomes in People with HIV: Potential Benefits, Challenges and Risks.” This funding opportunity will support research into how immunotherapy treatments for HIV impact the central nervous system (CNS), with the overarching goal of determining whether these therapies can help eliminate or reduce HIV persistence in the brain without inducing harmful neuroinflammatory effects. As the field of HIV treatment continues to evolve with innovations in immunotherapy, there is a critical need to understand the mechanisms by which such treatments interact with the CNS, especially given the complex barrier posed by the blood-brain interface and the distinct viral dynamics that may exist in neural compartments. The funding initiative will solicit biphasic research applications using the R21/R33 activity code. This mechanism allows for an exploratory phase (R21) followed by an expanded phase (R33), enabling researchers to both test initial hypotheses and expand on promising preliminary findings within a single grant framework. The intended studies are expected to identify the specific benefits and risks of using HIV immunotherapies in the CNS, assess potential neurotoxicity, and evaluate impacts on cognitive and neurological health in people living with HIV. Emphasis is placed on exploring CNS-specific factors, such as blood-brain barrier penetration, viral reservoir behavior, and immune responses, all of which may impact the effectiveness and safety of immunotherapies in neural tissues. The NOFO reflects NIMH’s commitment to advancing long-term strategies that can contribute to sustained HIV remission across all anatomical compartments, including the CNS. It encourages researchers with relevant expertise to prepare by forming collaborations and designing responsive proposals in anticipation of the formal opportunity release. Importantly, the program does not require cost sharing or matching contributions, broadening its accessibility to a wide range of institutions and investigators. The solicitation explicitly welcomes applications from researchers who are well-versed in immunotherapy, neuroHIV, and viral reservoir research. In terms of eligibility, this opportunity is open to a broad array of U.S.-based entities, including higher education institutions, state and local governments, public housing authorities, nonprofit organizations with or without IRS 501(c)(3) status, small businesses, for-profit organizations (excluding small businesses), independent school districts, and tribal governments and organizations. U.S. territories, regional organizations, faith-based and community-based organizations, and federal agencies are also eligible, demonstrating the program's inclusive and diverse approach to applicant participation. As this is a forecasted opportunity, specific submission instructions and components have yet to be finalized. However, the anticipated timeline suggests the NOFO will be published on or around August 17, 2026, with full applications due by October 22, 2026. Award notifications are expected by July 1, 2027, with funded projects beginning on the same date. There are currently no pre-application requirements such as letters of intent or concept papers noted in the forecast. Applications will likely be submitted through Grants.gov or the NIH ASSIST platform once the NOFO is live. For questions, potential applicants are directed to contact the Division of AIDS Research via email at [email protected]. This forecast allows ample lead time for developing strong, collaborative proposals that align with the program’s scientific goals. Interested investigators are advised to monitor Grants.gov and NIH notices for updates on the final NOFO release and application details.