Microglial Pathophysiology in Comorbid Substance Use Disorder (SUD) and HIV (R61/R33 Clinical Trial Not Allowed) | RFA DA 25 014

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.

• 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.

Apply for RFA DA 25 014

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