Opportunity Information: Apply for RFA DA 25 014
The National Institutes of Health (NIH) is offering a discretionary grant opportunity titled "Microglial Pathophysiology in Comorbid Substance Use Disorder (SUD) and HIV (R61/R33 Clinical Trial Not Allowed)" under funding opportunity number RFA-DA-25-014 (CFDA 93.279). The program uses a phased R61/R33 mechanism, which is generally designed to support an initial, milestone-driven exploratory or development stage (R61) followed by an expanded stage (R33) if predefined objectives are met. As stated in the title, clinical trials are not allowed, so the work is intended to be mechanistic and preclinical or translational in nature rather than interventional studies in human participants.
The central scientific purpose of the announcement is to clarify how microglia, the brain's resident immune cells, behave and contribute to neurological injury when HIV infection occurs alongside substance use disorder. The emphasis is on microglia that harbor HIV and how those infected or HIV-impacted microglial populations may drive or worsen neuropathologies specifically seen in people with both HIV and SUD. Rather than treating the brain as a single uniform tissue, the FOA is explicitly focused on brain-region specificity and cell-type specificity, meaning applicants are expected to resolve differences across distinct brain regions and to generate data that can separate microglial signals from other cell types in the nervous system.
A key deliverable highlighted in the description is the generation of microglial protein profiles, which implies proteomic characterization tailored to specific brain regions and microglial subpopulations in the context of HIV and SUD. The FOA then expects investigators to go beyond cataloging proteins by using molecular profiles and interaction networks to uncover mechanisms. In practical terms, this points toward systems-biology approaches that integrate proteomic signatures into pathway and network models, then test hypotheses about causal mechanisms linking HIV-harboring microglia to neural dysfunction, neuroinflammation, synaptic injury, neurodegeneration, or other relevant neuropathological outcomes that are heightened or distinct under comorbidity with substance use.
The opportunity is broadly open to many types of applicants. Eligible applicants include a wide range of U.S. governmental entities (state, county, city/township, special districts), public and state-controlled institutions of higher education, private institutions of higher education, independent school districts, and various categories of tribal governments and tribal organizations (including federally recognized tribal governments and other tribal organizations). It also includes public housing authorities/Indian housing authorities, nonprofit organizations (both with and without 501(c)(3) status, as long as they are not institutions of higher education in those nonprofit categories), for-profit organizations (other than small businesses), and small businesses. The FOA also explicitly names 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 (AANAPISISs). Faith-based and community-based organizations are listed as eligible, and the announcement allows participation by non-domestic (non-U.S.) entities (foreign organizations), as well as regional organizations and applicants located in a U.S. territory or possession. This broad eligibility suggests NIH is seeking to attract multidisciplinary teams spanning neuroscience, immunology, HIV research, addiction science, proteomics, and computational network biology, and it leaves room for both academic and non-academic research organizations to lead or collaborate.
From an administrative standpoint, the opportunity was created on 2023-07-19, and the original application due date listed is 2025-08-14. The agency is NIH, and the activity category is listed under education and health, consistent with NIH biomedical research priorities. An award ceiling and the expected number of awards are not provided in the source text you shared, so applicants would need to consult the full FOA for budget guidance, project period expectations, phase-specific limits (R61 versus R33), and any required milestones or go/no-go criteria for transition between phases.
Overall, this FOA is aimed at building a detailed, cell- and region-resolved molecular map of microglial proteins in HIV and SUD comorbidity and using that map to identify interaction networks and mechanistic pathways that explain how HIV-harboring microglia may uniquely contribute to brain disease in this dual-condition setting. The emphasis on protein profiling and network-driven mechanism building indicates NIH is looking for projects that combine high-resolution experimental biology with rigorous computational interpretation, culminating in clearer mechanistic explanations that could eventually inform future therapeutic strategies, even though clinical trials themselves are not supported under this particular announcement.Apply for RFA DA 25 014
- The National Institutes of Health in the education, health sector is offering a public funding opportunity titled "Microglial Pathophysiology in Comorbid Substance Use Disorder (SUD) and HIV (R61/R33 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 2023-07-19.
- Applicants must submit their applications by 2025-08-14. (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.
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Frequently Asked Questions (FAQs)
What is the title of this NIH funding opportunity?
The funding opportunity is titled "Microglial Pathophysiology in Comorbid Substance Use Disorder (SUD) and HIV (R61/R33 Clinical Trial Not Allowed)."
What is the funding opportunity number?
The funding opportunity number is RFA-DA-25-014.
What is the CFDA number associated with this opportunity?
The CFDA number listed is 93.279.
Which agency is offering this grant?
The offering agency is the National Institutes of Health (NIH).
What grant mechanism does this program use?
This program uses a phased R61/R33 mechanism. The R61 phase is typically an initial, milestone-driven exploratory or development stage, and the R33 phase is an expanded stage that may follow if predefined objectives or milestones are met.
How does the R61/R33 phased approach work in practice?
Based on the description provided, applicants should plan for an initial R61 stage focused on achieving specific, predefined milestones (often framed as go/no-go criteria). If those objectives are met, the project may transition into the R33 stage for broader or deeper follow-on work. Specific transition requirements, milestone formats, and phase-specific limits are not provided in the excerpt and would require review of the full FOA.
Are clinical trials allowed under this FOA?
No. Clinical trials are not allowed, as stated in the opportunity title ("Clinical Trial Not Allowed").
If clinical trials are not allowed, what kind of research is this meant to support?
The work is intended to be mechanistic and preclinical or translational in nature rather than interventional studies in human participants. The focus is on understanding biological mechanisms, particularly those involving microglia in the context of HIV and substance use disorder comorbidity.
What is the central scientific purpose of the opportunity?
The central purpose is to clarify how microglia (the brain's resident immune cells) behave and contribute to neurological injury when HIV infection occurs alongside substance use disorder (SUD). There is specific emphasis on microglia that harbor HIV and how HIV-infected or HIV-impacted microglial populations may drive or worsen neuropathologies in people with both HIV and SUD.
Why does this FOA focus on microglia?
Microglia are highlighted because they are the brain's resident immune cells and are implicated in neuroinflammation and neurological injury. The FOA specifically emphasizes microglia that harbor HIV and the possibility that these microglial populations uniquely contribute to brain disease in the setting of HIV and SUD comorbidity.
Does the FOA emphasize any specific biological context or comorbidity?
Yes. The FOA is specifically focused on comorbid substance use disorder (SUD) and HIV, with an emphasis on neuropathologies that are heightened or distinct when both conditions occur together.
Is the research expected to be brain-region specific?
Yes. The FOA explicitly focuses on brain-region specificity, meaning applicants are expected to resolve differences across distinct brain regions rather than treating the brain as a single uniform tissue.
Is the research expected to be cell-type specific?
Yes. The FOA is also explicitly focused on cell-type specificity. Applicants are expected to generate data that can separate microglial signals from other cell types in the nervous system.
What is a key deliverable mentioned in the opportunity description?
A key deliverable highlighted is the generation of microglial protein profiles, implying proteomic characterization tailored to specific brain regions and microglial subpopulations in the context of HIV and SUD.
Is the goal only to catalog microglial proteins?
No. The FOA expects investigators to go beyond cataloging proteins by using molecular profiles and interaction networks to uncover mechanisms linking HIV-harboring microglia to neuropathological outcomes.
What types of analytical approaches does the FOA appear to encourage?
The description points toward systems-biology approaches that integrate proteomic signatures into pathway and network models and then test hypotheses about causal mechanisms. This includes building and using molecular interaction networks to interpret microglial protein profiles in a mechanistic way.
What kinds of outcomes or disease processes are highlighted as relevant?
The FOA references mechanisms potentially linking HIV-harboring microglia to neural dysfunction, neuroinflammation, synaptic injury, neurodegeneration, and other neuropathological outcomes that may be heightened or distinct under HIV and SUD comorbidity.
Who is eligible to apply?
Eligibility is broad and includes many types of applicants, such as U.S. governmental entities (state, county, city/township, special districts), public and state-controlled institutions of higher education, private institutions of higher education, independent school districts, tribal governments and tribal organizations, public housing authorities/Indian housing authorities, nonprofit organizations (with or without 501(c)(3) status, in the categories listed), for-profit organizations (other than small businesses), and small businesses.
Are institutions serving underrepresented or specific communities explicitly listed as eligible?
Yes. The FOA explicitly names eligible 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 (AANAPISISs).
Are faith-based or community-based organizations eligible?
Yes. Faith-based and community-based organizations are listed as eligible applicants.
Can non-U.S. (foreign) organizations apply?
Yes. The announcement allows participation by non-domestic (non-U.S.) entities (foreign organizations). It also allows regional organizations and applicants located in a U.S. territory or possession.
Does the opportunity appear to encourage multidisciplinary teams?
The broad eligibility and the scientific emphasis suggest NIH is seeking multidisciplinary teams spanning areas such as neuroscience, immunology, HIV research, addiction science, proteomics, and computational/network biology. The excerpt does not impose team requirements, but the described scope naturally supports multidisciplinary collaboration.
When was this opportunity created?
The opportunity was created on 2023-07-19.
What is the application due date mentioned?
The original application due date listed is 2025-08-14.
What is the activity category for this opportunity?
The activity category is listed under education and health, consistent with NIH biomedical research priorities.
Is the award ceiling provided in the information shared?
No. An award ceiling is not provided in the source text shared.
Is the expected number of awards provided in the information shared?
No. The expected number of awards is not provided in the source text shared.
Where should applicants look for budget guidance and project period expectations?
Because award ceiling, expected number of awards, and detailed budget guidance are not provided in the excerpt, applicants would need to consult the full FOA for budget guidance, project period expectations, phase-specific limits (R61 vs. R33), and required milestones or go/no-go criteria for transition between phases.
What is the overall goal of the projects supported by this FOA?
Overall, the FOA aims to build a detailed, cell- and region-resolved molecular map of microglial proteins in HIV and SUD comorbidity and use that map to identify interaction networks and mechanistic pathways explaining how HIV-harboring microglia may uniquely contribute to brain disease in this dual-condition setting.
Does this FOA support therapeutic clinical testing?
No. The FOA does not support clinical trials. While the mechanistic findings could inform future therapeutic strategies, interventional clinical testing is not supported under this particular announcement.
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