Opportunities for HIV Cure Strategies at the Time of ART Initiation (R21 Clinical Trial Not Allowed) | PAR 23 296

Opportunity Information: Apply for PAR 23 296

The National Institutes of Health (NIH) is offering this discretionary grant opportunity, PAR 23 296, titled "Opportunities for HIV Cure Strategies at the Time of ART Initiation (R21 Clinical Trial Not Allowed)." The core aim is to support early-stage, exploratory research that can identify and develop HIV cure strategies that are practical and biologically compelling to use right when a person starts combination antiretroviral therapy (cART), and/or when cART is restarted after an analytical treatment interruption (ATI). The long-term endpoint NIH is pushing toward is sustained, treatment-free remission, meaning durable control of HIV without continuous antiretroviral medication.

A key feature of the announcement is its focus on timing: it prioritizes interventions that can be deployed at the ART starting line (or re-start line), when viral dynamics, immune responses, and reservoir formation or re-expansion may be more modifiable than later in infection or after long periods on suppressive therapy. In practical terms, the NOFO is meant to stimulate work on cure-oriented approaches that fit into real clinical workflows at ART initiation or re-initiation, rather than strategies that only make sense after years of stable suppression. This could include concept development, preclinical-to-translational studies, and other early-phase investigations that help determine whether an approach is feasible, safe in principle, and scientifically justified to pursue further in later-stage programs.

The funding mechanism is an NIH R21, which generally supports innovative, higher-risk/high-reward projects intended to generate strong preliminary data or proof-of-concept. Consistent with the title, "Clinical Trial Not Allowed," applications cannot propose independent clinical trials under this award. That typically means you can do mechanistic studies, model-based work, and other preparatory research, but you cannot run a clinical trial as the main activity of the grant. The work should be framed to advance a cure strategy toward readiness for later clinical evaluation without crossing into a clinical trial design that NIH would classify as prohibited under this specific NOFO.

From an administrative standpoint, the opportunity falls under the Health, Income Security and Social Services activity category and lists CFDA numbers 93.242, 93.855, and 93.865. The award ceiling is listed as $275,000. The opportunity was created on September 20, 2023, and the original closing date is September 7, 2026, which gives applicants a long runway to plan and submit, though applicants should still verify which specific receipt dates apply for their chosen submission cycle and confirm all current NIH policy requirements at the time of submission.

Eligibility is broad and includes many common NIH applicant types across government, academia, nonprofit, and industry. 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; public housing authorities and Indian housing authorities; Native American tribal organizations other than federally recognized tribal governments; nonprofits with or without 501(c)(3) status (excluding institutions of higher education in those categories as specified); for-profit organizations other than small businesses; and small businesses. The NOFO also explicitly highlights additional eligible applicant categories, including Alaska Native and Native Hawaiian Serving Institutions, Asian American Native American Pacific Islander Serving Institutions (AANAPISISs), Hispanic-serving Institutions, Historically Black Colleges and Universities (HBCUs), Tribally Controlled Colleges and Universities (TCCUs), faith-based or community-based organizations, eligible federal agencies, U.S. territories or possessions, and non-domestic (non-U.S.) entities and regional organizations. That breadth signals NIH interest in drawing ideas from a wide range of scientific and community contexts, including international settings where ART initiation and interruption/restart scenarios may be studied in different epidemiologic and health system conditions.

Overall, this NOFO is essentially a call for creative, scientifically grounded HIV cure strategy concepts that can be integrated at the moment ART begins or resumes, with the explicit purpose of moving the field closer to durable remission without ongoing therapy. It is positioned as a stepping-stone funding opportunity: it is meant to help teams generate the evidence and rationale needed to justify later, more definitive development and eventual clinical testing through mechanisms that do allow clinical trials.

• The National Institutes of Health in the health, income security and social services sector is offering a public funding opportunity titled "Opportunities for HIV Cure Strategies at the Time of ART Initiation (R21 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): 93.242, 93.855, 93.865.
• This funding opportunity was created on 2023-09-20.
• Applicants must submit their applications by 2026-09-07. (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 $275,000.00 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 PAR 23 296

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