Research to Address Systemic and Structural Barriers and Facilitators to Improve the HIV Pre-Exposure Prophylaxis (PrEP) Care Continuum for People Who Use Substances (R34 Clinical Trials Required) | RFA DA 26 004

Opportunity Information: Apply for RFA DA 26 004

This funding opportunity, titled "Research to Address Systemic and Structural Barriers and Facilitators to Improve the HIV Pre-Exposure Prophylaxis (PrEP) Care Continuum for People Who Use Substances (R34 Clinical Trials Required)" (RFA-DA-26-004), is a discretionary NIH grant aimed at improving how well PrEP is delivered, accessed, and used among people who use substances. PrEP is a proven, highly effective HIV prevention medication for people at risk through sex or injection drug use, yet real-world results have not matched its potential. In particular, awareness of PrEP, willingness or ability to start it, and ongoing adherence and persistence remain uneven and often low for people who use substances, even though this group may face heightened HIV exposure risk. The program is designed to support research that digs into why those gaps persist and then tests practical strategies to close them.

The central focus is on systemic and structural factors, meaning the opportunity is not only interested in individual-level behavior change, but also in the broader conditions that shape whether someone can realistically move through the PrEP care continuum. That continuum generally includes awareness and knowledge of PrEP, risk assessment and willingness to consider PrEP, linkage to a provider or program that can prescribe it, initiation of medication, adherence and persistence over time, and re-engagement if someone stops. For people who use substances, barriers can show up at many points: limited access to culturally competent and nonjudgmental care, stigma related to drug use, fragmented services between HIV prevention and substance use treatment, transportation and housing instability, insurance or documentation challenges, criminal legal involvement, pharmacy access issues, and clinic policies that unintentionally exclude people with complex lives. The grant is looking for projects that identify which of these systemic issues matter most in specific settings and then develop, implement, and evaluate strategies that address them in a way that fits the realities of the populations served.

The mechanism is an R34, which is typically used for early-stage, pilot, or proof-of-concept clinical research intended to support the next step toward larger-scale effectiveness studies. This particular notice specifies "Clinical Trials Required," so applicants should expect that the proposed work must include a clinical trial component, such as testing an intervention or implementation strategy in a real-world setting with measurable outcomes. In practice, that could include interventions that improve PrEP initiation and persistence by integrating PrEP into substance use treatment programs, syringe services programs, community health centers, emergency departments, mobile clinics, telehealth models, or pharmacy-based pathways. It could also involve structural or systems-level changes, such as new care navigation models, low-barrier prescribing workflows, stigma-reduction training paired with protocol changes, payment and billing supports, rapid start models, or strategies that coordinate PrEP with medications for opioid use disorder and harm reduction services. The key expectation is that projects will not just describe barriers, but will actively develop and test approaches that improve movement through the PrEP continuum for people who use substances.

The opportunity is administered by the National Institutes of Health, with activity areas spanning education and health, and it lists CFDA numbers 93.279, 93.310, and 93.313. The application deadline provided is March 12, 2025. The award ceiling is $225,000, indicating a modest budget consistent with pilot testing and preparatory work rather than a large multi-site trial. The notice lists expected awards, but the specific number is not provided in the source text. The opportunity was created on December 2, 2024, which helps situate it in the current policy and research context where the emphasis is increasingly on implementation, equity, and addressing structural drivers of health outcomes rather than relying solely on individual-level interventions.

Eligibility is broad and includes many types of organizations that commonly conduct community-engaged health research and implementation trials. Eligible applicants include state, county, and city or township 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; tribal organizations that are not federally recognized; public housing authorities and Indian housing authorities; nonprofits with and without 501(c)(3) status; for-profit organizations (other than small businesses); small businesses; and other entities. The opportunity also explicitly highlights additional eligible applicant categories, emphasizing inclusion of institutions and organizations that often serve populations heavily impacted by HIV and substance use-related harms. These include Alaska Native and Native Hawaiian Serving Institutions, Asian American Native American Pacific Islander Serving Institutions (AANAPISI), Hispanic-serving Institutions, Historically Black Colleges and Universities (HBCUs), Tribally Controlled Colleges and Universities (TCCUs), faith-based or community-based organizations, eligible federal agencies, regional organizations, U.S. territories or possessions, and even non-U.S. entities (foreign organizations). That wide eligibility list signals an intent to encourage proposals that are rooted in real service environments and communities, including settings where traditional academic medical centers may not be the main point of care.

Overall, the grant is about moving PrEP from being "available in theory" to being "workable in practice" for people who use substances by tackling the systems and structures that shape access and continuity. Competitive projects will likely be those that clearly identify a high-impact structural problem, partner closely with community and service organizations, design a feasible strategy that reduces friction at key steps in the PrEP continuum, and evaluate outcomes that reflect real improvements in PrEP awareness, initiation, adherence, and sustained use in the target population.

• The National Institutes of Health in the education, health sector is offering a public funding opportunity titled "Research to Address Systemic and Structural Barriers and Facilitators to Improve the HIV Pre-Exposure Prophylaxis (PrEP) Care Continuum for People Who Use Substances (R34 Clinical Trials Required)" and is now available to receive applicants.
• Interested and eligible applicants and submit their applications by referencing the CFDA number(s): 93.279, 93.310, 93.313.
• This funding opportunity was created on 2024-12-02.
• Applicants must submit their applications by 2025-03-12. (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 $225,000.00 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 26 004

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