Avant Garde/Avenir Awards for Investigators Conducting High Risk/High Reward Research on HIV and Substance Use (or Substance Use Disorders) (DP1 Clinical Trial Optional) | PAR 27 026

Opportunity Information: Apply for PAR 27 026

The Avant Garde/Avenir Awards for Investigators Conducting High Risk/High Reward Research on HIV and Substance Use (or Substance Use Disorders) (DP1 Clinical Trial Optional) is a National Institutes of Health (NIH) grant opportunity designed to fund bold, unconventional research ideas at the intersection of HIV and substance use. The central focus is on supporting projects that are intentionally high risk but also high payoff, meaning the NIH is looking for proposals that may challenge standard thinking or rely on novel approaches, yet have the potential to produce transformative advances if successful. The research supported under this program can span basic science, clinical research, translational studies, and implementation science, as long as the work is clearly relevant to improving outcomes for people affected by HIV who also use substances and/or have a substance use disorder.

In practical terms, the NOFO is aiming to accelerate progress across the full HIV continuum: prevention, diagnosis, treatment, and durable viral suppression. Applicants are encouraged to propose studies that generate new knowledge about how substance use influences HIV risk and progression, or that develop and test strategies that improve engagement in prevention and care among people who use drugs or have substance use disorders. Because the award emphasizes high impact, projects that could meaningfully reshape clinical practice, public health strategies, service delivery models, or scientific understanding of HIV and substance use are especially aligned with the intent of the program. The listing indicates that a clinical trial is optional, which means applicants may propose clinical trial activities if they are central to the research question, but it is not required to be competitive.

Eligibility is broad and includes many common applicant types that NIH typically allows. 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; Native American tribal governments (federally recognized) and tribal organizations (other than federally recognized tribal governments); public housing authorities and Indian housing authorities; nonprofit organizations with or without 501(c)(3) status (as long as they are not institutions of higher education in those categories); for-profit organizations (other than small businesses); and small businesses. The NOFO also explicitly allows foreign participation: non-U.S. entities may apply directly as foreign organizations, U.S. organizations may include non-U.S. components, and foreign components are permitted as defined under the NIH Grants Policy Statement. For applicants, that means international institutions and cross-border collaborations can be an acceptable and intentional part of the proposed work, provided all NIH policy requirements are met.

Administratively, this is a discretionary grant opportunity from the NIH, categorized under health, with CFDA number 93.279. The funding opportunity number is PAR-27-026, and the opportunity title emphasizes the Avant Garde/Avenir mechanism and the high risk/high reward nature of the research that NIH wants to stimulate. The posted information shows an original closing date of 2028-09-25, indicating a long application window typical of certain NIH program announcements, though applicants should still verify application due dates, cycles, and any specific submission instructions in the full NOFO text (especially since NIH opportunities often have multiple receipt dates and detailed requirements that are not captured in a brief listing). The award ceiling and expected number of awards are not specified in the excerpt provided, so applicants would need to consult the full announcement for budgetary caps, project period expectations, and any institute- or program-specific limits.

Overall, this opportunity is best understood as a competitive NIH funding pathway for investigators with ambitious ideas that could substantially improve HIV outcomes for people who use substances, whether through new biological insights, innovative clinical interventions, improved linkage and retention strategies, or real-world implementation approaches that close gaps between evidence and practice.

• The National Institutes of Health in the health sector is offering a public funding opportunity titled "Avant Garde/Avenir Awards for Investigators Conducting High Risk/High Reward Research on HIV and Substance Use (or Substance Use Disorders) (DP1 Clinical Trial Optional)" 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 2026-06-09.
• Applicants must submit their applications by 2028-09-25.
• 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 PAR 27 026

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