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)

The National Institute on Drug Abuse, a component of the National Institutes of Health within the U.S. Department of Health and Human Services, administers 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), funding opportunity PAR-27-026. The program supports exceptionally creative scientists proposing high-impact research at the intersection of HIV and substance use or substance use disorders. It supports innovative basic, clinical, translational, and implementation science intended to advance HIV prevention, diagnosis, treatment, virus suppression, and cure for people who use substances or have substance use disorders. Clinical trials are optional. Projects must propose pioneering research aligned with NIH HIV/AIDS Research Priorities and clearly establish the nexus between HIV and substance use. Proposed work cannot simply expand an ongoing funded project and should instead pursue ideas and approaches substantially different from those currently pursued by the investigator or others in the field. Applications must explain why substance use is relevant or significant to the HIV research, how the methodology addresses substance use, and how anticipated outcomes address the intersection of substance use and HIV. Examples include creative HIV transmission prevention strategies for people who use substances, approaches to close gaps in HIV pre-exposure prophylaxis and care cascades, research addressing HIV-related comorbidities, and mechanistic research informing HIV treatment and cure. Applications focused solely on alcohol use in the context of HIV are non-responsive. Studies that evaluate, support, or promote substance use disorder harm reduction models are also non-responsive. Application budgets are limited to 700000 in total costs per year for established investigators and 375000 per year for early stage investigators. The maximum project period is five years. Applicants are instructed to enter a five-year total federal request of 3500000 for established investigators or 1875000 for early stage investigators. Applicable Facilities and Administrative costs are determined at the time of award and are not included in the budget request. A detailed budget is not requested and will not be accepted. Funds may support personnel, including collaborators, supplies, equipment, sub-contracts, and other allowable costs. The opportunity does not require cost sharing. Established investigators must commit at least 35 percent or 4.2 person months of research effort to the DP1 project, while early stage investigators must commit at least 25 percent or 3 person months. Eligible organizations include public and private institutions of higher education, nonprofit organizations with or without 501(c)(3) status, small businesses and other for-profit organizations, state and local governments, special district governments, tribal governments and organizations, eligible federal agencies, U.S. territories or possessions, independent school districts, public and Indian housing authorities, faith-based or community-based organizations, regional organizations, and foreign organizations. Non-U.S. components of U.S. organizations and foreign components are permitted. However, applications involving foreign subawards or subcontracts are noncompliant and will not be considered for funding. Applicant organizations must maintain the required SAM, eRA Commons, and Grants.gov registrations, and PD/PIs must have an eRA Commons account and linked ORCID identifier. Applications must be submitted electronically using NIH ASSIST, Grants.gov Workspace, or an institutional system-to-system solution, with subsequent tracking through eRA Commons. The application is New and uses the DP1 activity code. The Research Strategy consists of an Essay rather than Specific Aims or a detailed scientific plan. Required essay sections include the project title, statement of research effort commitment, project description, evidence of innovation, explanation of how the research differs from the applicant's past or current work, and compatibility with the goals of the Avant-Garde/Avenir Award Program for HIV Research. Other applicable materials include collaborator information in the cover letter, Current and Pending Other Support for the PD/PI, letters of support from significant collaborators, Resource Sharing Plan, Data Management and Sharing Plan when scientific data will be generated, applicable human subjects and clinical trials information, and other required NIH forms. PD/PIs must also arrange for exactly three confidential reference letters submitted separately by referees. Missing or late reference letters will make the application incomplete. Peer review emphasizes the importance and potential impact of the scientific problem, novelty and innovation of the approach, and the applicant's potential to conduct creative and innovative research. Reviewers assess overall impact as well as Significance, Investigator, Innovation, Approach, and Environment, together with applicable clinical trial and additional review criteria. Final selections are made by the Director of NIDA based on peer review outcomes, concurrence of the National Advisory Council on Drug Abuse, and programmatic considerations. Funding decisions also consider scientific and technical merit, availability of funds, and relevance to program priorities. The opportunity opened for submissions on August 25, 2026. Applications and the required reference letters for the current cycle are due September 25, 2026 at 5:00 PM local time of the applicant organization. Additional annual application deadlines are September 25, 2027 and September 25, 2028, with the opportunity expiring September 26, 2028. The 2026 cycle anticipates scientific merit review in March 2027, advisory council review in May 2027, and an earliest start date in July 2027, although the application instructions specify an April 1 proposed project start date. Scientific and research questions may be directed to NIDA HIV Program Staff at NIDAHIVProgram@mail.nih.gov. Financial and grants management questions may be directed to nidagmbemail@nida.nih.gov.

Center the application on a pioneering, high-risk, potentially transformative HIV research direction with a clearly defined substance-use nexus. Explain why substance use is significant, how the methodology addresses it, and how outcomes address the HIV and substance-use intersection. Show concrete evidence of innovation and explain how the work differs substantially from the applicant's past or current work and from work already pursued in the field. Explain why the project is uniquely suited to the DP1 mechanism rather than a traditional NIH mechanism. Include the required effort-commitment statement or the application will be returned without review. Arrange exactly three reference letters before the deadline and monitor their receipt in eRA Commons. Do not focus solely on alcohol use in HIV and do not propose studies that evaluate, support, or promote SUD harm reduction models, because such applications are non-responsive.