Role of Myeloid Cells in Persistence and Eradication of HIV-1 Reservoirs from the Brain (R01 Clinical Trial Not Allowed) | RFA MH 20 701

Opportunity Information: Apply for RFA MH 20 701

The National Institutes of Health (NIH) funding opportunity RFA-MH-20-701, titled "Role of Myeloid Cells in Persistence and Eradication of HIV-1 Reservoirs from the Brain (R01 Clinical Trial Not Allowed)," is a discretionary research grant announcement that supports R01 projects focused on how HIV-1 persists in the brain within myeloid-lineage cells and how those reservoirs might be effectively targeted or eliminated. The central scientific theme is HIV-1 persistence in the central nervous system (CNS), particularly in myeloid cells such as microglia and brain macrophages, and the development or testing of strategies aimed at reducing or eradicating these reservoirs. The FOA is positioned to advance both basic science (mechanistic understanding of viral persistence, cellular biology, and host-pathogen interactions) and translational research (approaches that can move toward practical interventions), with an emphasis on the unique challenges of addressing HIV-1 that remains in the brain even when systemic infection is well controlled.

The announcement is specifically an R01 mechanism and explicitly states that clinical trials are not allowed under this FOA, meaning applicants should propose non-clinical-trial studies. In practice, that typically aligns with laboratory-based investigations, studies using animal models, in vitro and ex vivo human tissue work, advanced imaging or molecular profiling approaches, and translational experiments that do not meet the NIH definition of a clinical trial. The intent is to encourage rigorous investigation into the mechanisms that allow HIV-1 to remain in CNS myeloid cells, including factors such as immune privilege, limited drug penetration into the brain, cell longevity and self-renewal, viral latency or low-level replication, inflammation-driven persistence, and the role of the CNS environment in shaping reservoir dynamics. On the eradication side, projects might explore therapeutic concepts and targeting strategies relevant to the brain myeloid compartment, such as approaches to reverse latency, selectively eliminate infected cells, modulate innate immune pathways, enhance clearance mechanisms, or improve delivery of therapeutics across or around the blood-brain barrier, as long as the work does not constitute a clinical trial.

NIH indicates that both domestic and international research settings are of interest, which broadens the range of possible collaborations, cohorts, specimens, and model systems that can be leveraged. The FOA also encourages, though does not require, multidisciplinary research teams and collaborative alliances. That encouragement reflects the reality that HIV persistence in the brain spans multiple specialties, often benefiting from expertise in neuroimmunology, virology, myeloid cell biology, neuropathology, pharmacology, systems biology, bioinformatics, and translational therapeutics. While a single-investigator application could be responsive, proposals that integrate complementary methods (for example, combining single-cell sequencing with virologic assays and CNS-relevant model systems) are clearly aligned with the FOA's emphasis on tackling a complex reservoir problem from multiple angles.

Eligibility is broad and includes many organization types across the public, private, nonprofit, and academic sectors. Eligible applicants listed include state, county, city or township, and special district governments; independent school districts; public and state-controlled institutions of higher education; private institutions of higher education; federally recognized Native American tribal governments; Native American tribal organizations (other than federally recognized tribal governments); public housing authorities/Indian housing authorities; nonprofits with and without 501(c)(3) status (other than institutions of higher education); for-profit organizations (other than small businesses); and small businesses. The FOA additionally highlights other eligible applicant categories such as Alaska Native and Native Hawaiian Serving Institutions, Asian American Native American Pacific Islander Serving Institutions (AANAPISIs), Hispanic-serving Institutions, Historically Black Colleges and Universities (HBCUs), Tribally Controlled Colleges and Universities (TCCUs), faith-based or community-based organizations, U.S. territories or possessions, certain tribal governments that are not federally recognized, eligible federal agencies, and non-U.S. entities (foreign organizations) and regional organizations. Taken together, this signals a strong interest in inclusive participation and in drawing on diverse institutional strengths and research settings, including those that may have unique access to populations, specimens, or specialized neuroscience and immunology infrastructure.

From an administrative standpoint, the opportunity is categorized under education and health-related funding activity areas and is associated with CFDA numbers 93.242, 93.279, and 93.853. The NIH is the sponsoring agency. The FOA creation date is September 24, 2020, and the original closing date listed is January 8, 2021. The listing does not provide an award ceiling or expected number of awards in the provided source data, so applicants would normally refer to the full FOA text and NIH budgeting policies for guidance on typical R01 scale and any institute-specific budget expectations.

Overall, this FOA is aimed at accelerating progress toward understanding and ultimately overcoming one of the most difficult barriers to an HIV cure: the persistence of HIV-1 within brain-resident or brain-associated myeloid cell reservoirs. It supports research designed to clarify how these reservoirs form and persist under antiretroviral therapy, what viral and host mechanisms sustain them, and which scientifically grounded strategies might reduce or eradicate infected myeloid cells in the CNS while accounting for the unique biology and protective barriers of the brain.

• 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 (R01 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.)
• 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 20 701

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