Silencing of HIV-1 Proviruses (R61/R33) | RFA AI 17 013

Opportunity Information: Apply for RFA AI 17 013

The National Institutes of Health (NIH) grant opportunity titled "Silencing of HIV-1 Proviruses (R61/R33)" (Funding Opportunity Number RFA AI 17 013) supports early-stage, high-potential research aimed at a long-standing challenge in HIV treatment: the persistence of HIV in a latent, integrated form (the provirus) inside host cells. Even when antiretroviral therapy suppresses active viral replication, proviruses can remain hidden and capable of reactivating, which is a major barrier to curing HIV. This FOA focuses on a "block-and-lock" style strategy, meaning it is interested in approaches that drive HIV into a deep, durable state of transcriptional silence rather than trying to shock it out of latency.

The scientific goal of the program is to fund exploratory and developmental projects that identify and optimize either small molecules or RNA-based agents that can engage the host cell's epigenetic machinery to produce long-term or potentially permanent epigenetic silencing of HIV-1 proviruses. In practical terms, this means applicants are expected to look for interventions that modify or recruit host factors involved in chromatin regulation (for example, pathways that control histone modifications, DNA methylation, chromatin remodeling, or other transcriptional control systems) in a way that keeps HIV proviral DNA locked down and unable to restart active infection. The emphasis on host epigenetic machinery reflects an interest in targeting cellular systems that regulate proviral transcriptional competence, potentially making silencing more stable than approaches that act only on viral proteins.

The mechanism is bi-phasic (R61/R33), which is designed to support a progression from initial, milestone-driven exploration into a more advanced development phase if the early aims succeed. The first phase (R61) is generally used for proof-of-concept and feasibility work, such as discovering candidate compounds or RNAs, developing or validating assays, demonstrating target engagement, showing early evidence of proviral silencing, and establishing initial structure-activity relationships or optimization parameters. The second phase (R33) is intended for projects that meet the R61 milestones and are ready to move into more robust optimization and development activities, such as improving potency and selectivity, refining delivery strategies for RNA-based approaches, expanding validation across relevant cell models, and generating deeper evidence that silencing is durable and mechanistically tied to epigenetic regulation. The overall structure is meant to reduce risk for promising but still-developing ideas by creating a clear gateway between exploratory work and more resource-intensive development.

From an administrative perspective, this is a discretionary grant program under NIH, with activity categories spanning education and health, and CFDA numbers listed as 93.242, 93.279, 93.855, and 93.856. The opportunity was created on 2017-05-17, and the original closing date was 2017-12-06. The listed award ceiling is $500,000. While the number of expected awards is not specified in the provided source data, the budget cap gives a sense of the scale NIH envisioned for individual projects under this announcement.

Eligibility is broad and includes many types of U.S. organizations and governmental units, reflecting NIH's aim to attract a wide range of scientific and translational expertise. 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 Native American tribal organizations (other than federally recognized tribal governments); public housing authorities and Indian housing authorities; nonprofits with and without 501(c)(3) status (excluding institutions of higher education in those nonprofit categories as listed); for-profit organizations other than small businesses; and small businesses, along with other applicants as allowed. In addition, the FOA explicitly highlights other eligible applicant categories such as Alaska Native and Native Hawaiian Serving Institutions; Asian American Native American Pacific Islander Serving Institutions (AANAPISIs); Historically Black Colleges and Universities (HBCUs); Hispanic-serving Institutions; Tribally Controlled Colleges and Universities (TCCUs); faith-based or community-based organizations; eligible federal agencies; regional organizations; U.S. territories or possessions; Indian/Native American tribal governments other than federally recognized entities; and non-domestic (non-U.S.) entities, meaning foreign organizations can also apply.

Overall, the opportunity is best understood as NIH support for pipeline-style research that starts with discovery and moves toward optimization of agents that can enforce durable epigenetic repression of HIV proviruses. It is geared toward applicants who can connect mechanistic epigenetics with rigorous HIV latency models and can propose clear milestones demonstrating that their candidate small molecule or RNA not only reduces proviral transcription, but does so through definable interactions with host epigenetic systems in a way that could plausibly remain stable over time.

• The National Institutes of Health in the education, health sector is offering a public funding opportunity titled "Silencing of HIV-1 Proviruses (R61/R33)" and is now available to receive applicants.
• Interested and eligible applicants and submit their applications by referencing the CFDA number(s): 93.242, 93.279, 93.855, 93.856.
• This funding opportunity was created on 2017-05-17.
• Applicants must submit their applications by 2017-12-06. (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 $500,000.00 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.

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