Ex Vivo Models for Studies at the Intersection of HIV and Poly-Substance Use (R01 Clinical Trial Not Allowed) | RFA DA 24 001

Opportunity Information: Apply for RFA DA 24 001

The National Institutes of Health (NIH) is soliciting R01 research grant applications through the funding opportunity titled "Ex Vivo Models for Studies at the Intersection of HIV and Poly-Substance Use (R01 Clinical Trial Not Allowed)" (Funding Opportunity Number RFA-DA-24-001). The scientific goal is to better explain how HIV contributes to HIV-associated neurological disorders (HAND), especially in the real-world context where many people living with HIV also use multiple addictive substances. This announcement focuses on building and using human-relevant ex vivo experimental systems rather than clinical trials, with the intent of producing mechanistic insights that are difficult to obtain from human participants or standard animal models alone.

A central requirement of the opportunity is the use of ex vivo culturing platforms derived from human induced pluripotent stem cells (hiPSCs). Applicants are expected to leverage these human stem cell-based systems to model key brain cell types and their interactions in controlled laboratory settings, while also incorporating exposure to addictive substances. The emphasis is on understanding neuroimmune and neuronal-glial mechanisms that may drive or worsen HAND, including how immune signaling in the brain and communication between neurons and glial cells (such as astrocytes, microglia, and oligodendrocyte-lineage cells) contribute to injury, inflammation, synaptic dysfunction, and circuit-level changes. In other words, the FOA is pointing investigators toward mechanistic, cell- and network-informed explanations for how HIV-related factors and substance use together alter brain biology.

Methodologically, the FOA highlights the need for unbiased and reproducible approaches, with particular attention to genetics and epigenetics as well as cellular behavior across biological scales. Competitive projects will typically be designed to interrogate molecular and regulatory changes (including genetic variation effects and epigenetic remodeling), characterize neuroglial and neuroimmune activities, and connect those findings to functional outcomes that can be measured from the single-cell level up through neural circuits. The language around "unbiased" analysis signals an interest in modern discovery-oriented approaches (for example, robust single-cell or multi-omic profiling, systematic perturbation strategies, and rigorous computational pipelines), but the key expectation is that conclusions are not overly dependent on narrow marker selection or one-off observations and that results are designed to be replicable across experiments, lines, and conditions.

This is an NIH discretionary grant opportunity using the R01 mechanism, and it is explicitly marked "Clinical Trial Not Allowed," meaning applications should not propose prospective studies in which human participants are assigned to interventions to evaluate health-related outcomes as defined by NIH clinical trial criteria. The activity category is listed under Education and Health, and the CFDA number associated with the opportunity is 93.279. The posting indicates an original closing date of 2025-08-13, giving applicants a defined deadline to prepare a full R01 submission that fits the scientific scope and administrative rules described in the announcement.

Eligibility is broad across U.S.-based organizational types. 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; small businesses; and other organizations that meet NIH eligibility requirements. The FOA also explicitly calls out additional eligible applicant 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. This wide eligibility list reflects NIH's intent to attract multidisciplinary teams that can combine stem cell biology, neuroscience, immunology, addiction science, and computational analysis.

At the same time, the announcement places clear limits on foreign involvement. Non-domestic (non-U.S.) entities and foreign institutions are not eligible to apply as the primary applicant organization, and non-domestic components of U.S. organizations are also not eligible to apply. However, "foreign components" are allowed as defined in the NIH Grants Policy Statement, meaning a U.S.-based applicant may include certain scientifically justified collaborations or work elements conducted outside the U.S. under NIH's foreign component rules, provided the overall application remains compliant with NIH policy.

In practical terms, this FOA is aimed at researchers who can build credible hiPSC-derived ex vivo brain platforms and use them to dissect how HIV-related biology and poly-substance exposure jointly shape neuroimmune responses, neuron-glia dynamics, and functional neural outcomes. Applications that are likely to align well will typically emphasize rigorous experimental design, reproducibility plans, and a clear strategy for linking molecular and cellular findings to higher-order neural function, while staying firmly on the mechanistic, preclinical side rather than proposing human clinical interventions.

• The National Institutes of Health in the education, health sector is offering a public funding opportunity titled "Ex Vivo Models for Studies at the Intersection of HIV and Poly-Substance Use (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): 93.279.
• This funding opportunity was created on 2023-02-28.
• Applicants must submit their applications by 2025-08-13. (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 DA 24 001

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