Role of Myeloid Cells in Persistence and Eradication of HIV-1 Reservoirs from the Brain (R21 Clinical Trial Not Allowed) | RFA MH 20 702

Opportunity Information: Apply for RFA MH 20 702

The NIH funding opportunity RFA-MH-20-702, titled "Role of Myeloid Cells in Persistence and Eradication of HIV-1 Reservoirs from the Brain (R21 Clinical Trial Not Allowed)," supports research focused on a specific and difficult barrier to curing HIV: the persistence of HIV-1 in myeloid cells within the central nervous system (CNS). The central aim is to encourage studies that explain how HIV can remain in these brain-associated myeloid cell populations over time and to develop or test strategies that could target, reduce, or eliminate this reservoir. The FOA is built around the idea that even when HIV is well controlled in the blood with antiretroviral therapy, long-lived or protected cellular reservoirs, including those in the brain, may allow the virus to persist and potentially reignite infection if treatment stops.

The scope includes both basic and translational research. On the basic science side, applicants are expected to explore mechanisms that enable HIV-1 persistence in myeloid-lineage cells, which can include cells such as macrophages and microglia that reside in or traffic through the brain. This can involve questions about how infection is established in these cells, what cellular or viral factors promote latency or low-level replication, how the CNS environment influences infection and immune evasion, and why these reservoirs can be difficult for drugs or immune responses to clear. On the translational side, the FOA is interested in practical strategies to attack this reservoir, which may include approaches to improve drug delivery across the blood-brain barrier, immune-based targeting of infected myeloid cells, or other interventions aimed at reservoir reduction or eradication in the CNS. The announcement explicitly welcomes work conducted in both domestic and international settings, reflecting the global nature of HIV and the value of diverse cohorts, samples, and research infrastructures.

This particular FOA uses the R21 research grant mechanism, which is typically used for exploratory, early-stage projects. The announcement emphasizes high-risk/high-reward ideas, including projects that may not yet have extensive preliminary data, or projects that can leverage existing datasets or stored specimens to generate new insights. In parallel, NIH released a companion opportunity (RFA-MH-20-701) using the R01 mechanism for applicants who already have stronger preliminary evidence and want to pursue a more developed research plan. For RFA-MH-20-702, the R21 framing is meant to help investigators test innovative hypotheses, develop new tools or models, or generate foundational data that could later support larger-scale studies.

Clinical trials are not allowed under this R21 FOA, meaning the supported work must stay on the non-clinical-trial side of the research spectrum. That said, the announcement still allows for translational research and can involve human-derived materials, observational analyses, or other non-trial activities, as long as they do not meet the definition of a clinical trial. The FOA also encourages multidisciplinary teams and collaborative alliances, recognizing that CNS HIV reservoirs sit at the intersection of virology, immunology, neurobiology, pharmacology, and clinical neuroscience. Collaboration is encouraged but not required, so single-investigator teams with the right expertise and approach can still be competitive.

From an administrative standpoint, the opportunity is offered by the National Institutes of Health and is categorized as a discretionary grant program in health-related research (CFDA numbers 93.242, 93.279, 93.853). The original closing date listed is January 8, 2021, and the posted award ceiling is $200,000, consistent with the smaller, exploratory nature of an R21 award. The FOA lists a broad set of eligible applicants, spanning public and private institutions of higher education, federal agencies, state and local governments, independent school districts, small businesses and other for-profit organizations (other than small businesses), and nonprofit organizations with or without 501(c)(3) status. It also highlights eligibility for a range of mission-driven or underrepresented institution types and organizations, including HBCUs, Hispanic-serving institutions, tribally controlled colleges and universities, Alaska Native and Native Hawaiian serving institutions, AANAPISI institutions, faith-based and community-based organizations, U.S. territories and possessions, and non-U.S. (foreign) entities and regional organizations. This broad eligibility is intended to widen participation and enable the best ideas and capabilities to contribute, regardless of geography or organizational structure.

Overall, the FOA is aimed at accelerating progress toward understanding and ultimately eliminating HIV-1 reservoirs in the brain by focusing on myeloid cells, supporting innovative early-stage studies, and bringing together cross-disciplinary perspectives to tackle a reservoir that is widely viewed as one of the more challenging frontiers in HIV cure research.

• The National Institutes of Health in the education, health sector is offering a public funding opportunity titled "Role of Myeloid Cells in Persistence and Eradication of HIV-1 Reservoirs from the Brain (R21 Clinical Trial Not Allowed)" and is now available to receive applicants.
• Interested and eligible applicants and submit their applications by referencing the CFDA number(s): 93.242, 93.279, 93.853.
• This funding opportunity was created on 2020-09-24.
• Applicants must submit their applications by 2021-01-08. (Agency may still review applications by suitable applicants for the remaining/unused allocated funding in 2026.)
• Each selected applicant is eligible to receive up to $200,000.00 in funding.
• Eligible applicants include: State governments, County governments, City or township governments, Special district governments, Independent school districts, Public and State controlled institutions of higher education, Native American tribal governments (Federally recognized), Public housing authorities/Indian housing authorities, Native American tribal organizations (other than Federally recognized tribal governments), Nonprofits having a 501 (c) (3) status with the IRS, other than institutions of higher education, Nonprofits that do not have a 501 (c) (3) status with the IRS, other than institutions of higher education, Private institutions of higher education, For-profit organizations other than small businesses, Small businesses, Others.

Apply for RFA MH 20 702

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