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

Frequently Asked Questions (FAQs)

What is the title of this NIH funding opportunity?

The funding opportunity is titled "Ex Vivo Models for Studies at the Intersection of HIV and Poly-Substance Use (R01 Clinical Trial Not Allowed)" and it uses the R01 research project grant mechanism.

What is the funding opportunity number?

The funding opportunity number is RFA-DA-24-001.

Which agency is offering this opportunity?

This opportunity is offered by the National Institutes of Health (NIH).

What is the main scientific goal of the FOA?

The goal is to better explain how HIV contributes to HIV-associated neurological disorders (HAND), especially in real-world settings where many people living with HIV also use multiple addictive substances. The FOA emphasizes mechanistic insights that are difficult to obtain from human participants or standard animal models alone.

What kinds of research approaches does this FOA prioritize?

The FOA prioritizes human-relevant, mechanistic, ex vivo experimental systems, with a strong emphasis on reproducible and unbiased approaches that can connect molecular and cellular findings to functional outcomes measured from single cells through neural circuits.

Are clinical trials allowed under this FOA?

No. The FOA is explicitly marked "Clinical Trial Not Allowed." 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.

What is meant by "ex vivo" in the context of this FOA?

In this FOA, "ex vivo" refers to experimental culturing platforms built and studied in controlled laboratory settings using human-relevant cells and tissues, rather than conducting prospective intervention studies in human participants.

Is use of human induced pluripotent stem cells (hiPSCs) required?

Yes. A central requirement 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.

What kinds of brain biology is the FOA trying to model?

The FOA is focused on modeling neuroimmune and neuronal-glial mechanisms that may drive or worsen HAND, including immune signaling in the brain and communication between neurons and glial cells that contributes to injury, inflammation, synaptic dysfunction, and circuit-level changes.

Which glial or brain cell types are specifically mentioned?

The FOA mentions glial cell types such as astrocytes, microglia, and oligodendrocyte-lineage cells, in addition to neurons and their interactions.

Does the FOA require incorporating exposure to addictive substances?

Yes. The FOA emphasizes incorporating exposure to addictive substances in the ex vivo systems to study how HIV-related biology and poly-substance exposure jointly affect brain mechanisms relevant to HAND.

What does the FOA mean by focusing on the "intersection" of HIV and poly-substance use?

It means studying how HIV-related factors and exposure to multiple addictive substances together alter brain biology, particularly through neuroimmune responses and neuron-glia interactions, in ways that may contribute to neurological impairment associated with HIV.

What types of analyses are encouraged by the FOA?

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. It signals interest in discovery-oriented strategies where conclusions are not overly dependent on narrow marker selection or one-off observations.

Does the FOA emphasize genetics and epigenetics?

Yes. Competitive projects are expected to interrogate molecular and regulatory changes, including genetic variation effects and epigenetic remodeling, and relate those changes to neuroglial, neuroimmune, and functional outcomes.

What does the FOA mean by "unbiased" approaches?

Based on the FOA language, "unbiased" indicates approaches designed for robust discovery and reproducibility, rather than relying only on a limited set of pre-selected markers or isolated observations. The expectation is that results are replicable across experiments, cell lines, and conditions.

What does the FOA say about reproducibility?

The FOA stresses reproducible approaches and rigorous design so that findings are dependable across experiments and conditions, including across different hiPSC lines and exposure conditions.

What grant mechanism is being used?

This is an NIH discretionary grant opportunity using the R01 mechanism.

What is the CFDA number associated with this opportunity?

The CFDA number associated with the opportunity is 93.279.

What activity category is listed for this opportunity?

The activity category is listed under Education and Health.

What is the application deadline?

The posting indicates an original closing date of 2025-08-13.

Who is eligible to apply?

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.

Are minority-serving institutions explicitly included as eligible applicants?

Yes. The FOA explicitly calls out additional eligible applicant categories, including 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).

Are faith-based or community-based organizations eligible?

Yes. The eligibility list explicitly includes faith-based or community-based organizations.

Are U.S. territories or possessions eligible to apply?

Yes. The FOA includes U.S. territories or possessions among eligible applicant categories.

Can foreign (non-U.S.) institutions apply as the primary applicant?

No. Non-domestic (non-U.S.) entities and foreign institutions are not eligible to apply as the primary applicant organization.

Can a non-U.S. component of a U.S. organization apply?

No. Non-domestic components of U.S. organizations are also not eligible to apply as the applicant organization.

Are collaborations or work conducted outside the U.S. allowed at all?

Yes, foreign components are allowed as defined in the NIH Grants Policy Statement. A U.S.-based applicant may include scientifically justified collaborations or work elements conducted outside the U.S. under NIH foreign component rules, as long as the overall application is compliant with NIH policy.

What kinds of research teams or disciplines does this FOA seem to be aiming to attract?

The FOA reflects an intent to attract multidisciplinary teams that can combine stem cell biology, neuroscience, immunology, addiction science, and computational analysis to produce mechanistic insights using hiPSC-derived ex vivo brain platforms.

What outcomes or readouts does the FOA want projects to connect to?

The FOA emphasizes linking molecular and regulatory changes and cellular behaviors to functional outcomes, with measurements spanning from single-cell readouts up through neural circuits.

What is the overall scope boundary described by the FOA?

The scope is firmly on mechanistic, preclinical ex vivo research using hiPSC-derived platforms, rather than proposing clinical trials or other prospective intervention studies in humans.