Modeling HIV Neuropathology Using Microglia from Human iPSC and Cerebral Organoids (R21-Clinical Trials Not Allowed) | RFA DA 19 010

Opportunity Information: Apply for RFA DA 19 010

The National Institutes of Health (NIH) released this discretionary grant opportunity, RFA-DA-19-010, titled "Modeling HIV Neuropathology Using Microglia from Human iPSC and Cerebral Organoids (R21-Clinical Trials Not Allowed)," to support early-stage, exploratory research on HIV-associated neurocognitive disorders (HAND) in the modern treatment era. The focus is on understanding the cellular and molecular mechanisms that drive neuropathophysiology in people living with HIV who are on long-term combination antiretroviral therapy (cART). Rather than relying solely on animal models or postmortem tissue, the FOA emphasizes the use of human stem cell-based systems, specifically patient-derived induced pluripotent stem cell (iPSC) lines that can be differentiated into induced microglia and incorporated into cerebral organoids. These platforms are intended to better capture human-specific neuroimmune interactions and help clarify how HIV infection, residual viral activity, inflammation, and/or treatment-related factors may contribute to ongoing cognitive and neurological complications despite viral suppression.

The scientific approach encouraged by this announcement centers on recreating key elements of the brain environment in vitro so applicants can probe microglia-driven processes, neuron-glia signaling, inflammatory pathways, synaptic changes, and other neurobiological mechanisms implicated in HAND under cART conditions. By using induced microglia and cerebral organoids generated from patient-derived iPSCs, researchers can potentially compare phenotypes across different donor backgrounds, examine how microglia respond to HIV-related stimuli, and test mechanistic hypotheses about chronic neuroinflammation, neurotoxicity, or disrupted brain homeostasis. The intent is not to run human subject interventions, but to generate foundational mechanistic insights and model systems that can inform later translational work.

This FOA uses the NIH R21 mechanism, which is designed for exploratory or developmental projects that can open new lines of investigation, generate proof-of-concept findings, or establish feasibility for innovative model systems. The opportunity explicitly states that clinical trials are not allowed, meaning the proposed work should not include prospective assignment of human participants to an intervention to evaluate health-related outcomes. The listed award ceiling is $200,000, reflecting the smaller, high-impact, early-stage nature typical of R21 awards. The original closing date for applications was December 18, 2018, and the opportunity was created on September 7, 2018.

Eligibility is broad across U.S.-based organizational types, reflecting NIH norms for many research FOAs. Eligible applicants include state, county, and local governments; 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 announcement also highlights additional eligible categories such as Historically Black Colleges and Universities (HBCUs), Hispanic-serving Institutions, Tribally Controlled Colleges and Universities (TCCUs), Alaska Native and Native Hawaiian Serving Institutions, and Asian American Native American Pacific Islander Serving Institutions (AANAPISIs), as well as faith-based or community-based organizations, eligible federal agencies, regional organizations, and U.S. territories or possessions.

At the same time, the FOA places clear restrictions on foreign involvement. Non-domestic (non-U.S.) entities and foreign institutions are not eligible to apply, non-domestic components of U.S. organizations are not eligible, and foreign components as defined in the NIH Grants Policy Statement are not allowed. In practical terms, this means the applicant organization must be domestic and the proposed work must be carried out without foreign components under NIH policy definitions.

Overall, the opportunity is aimed at advancing the field’s ability to model and dissect HAND-related neuropathology in a controlled human-relevant experimental setting, with an emphasis on microglia biology and brain-like organoid systems derived from patient iPSCs, specifically within the context of long-term cART where persistent neurological complications remain a major unmet need.

• The National Institutes of Health in the education, health sector is offering a public funding opportunity titled "Modeling HIV Neuropathology Using Microglia from Human iPSC and Cerebral Organoids (R21-Clinical Trials Not Allowed)" and is now available to receive applicants.
• Interested and eligible applicants and submit their applications by referencing the CFDA number(s): 93.279.
• This funding opportunity was created on 2018-09-07.
• Applicants must submit their applications by 2018-12-18. (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 DA 19 010

[Watch] Creating a grant proposal using the step-by-step wizard inside the applicant portal: