Defining Mechanisms of HIV Induced Inflammation and Immune Activation During Suppressive Antiretroviral Therapy (ART) (R01 Clinical Trial Not Allowed) | RFA AI 23 018

Opportunity Information: Apply for RFA AI 23 018

This NIH grant opportunity (RFA AI 23 018) is an R01 research funding announcement focused on a persistent problem in HIV medicine: even when antiretroviral therapy (ART) suppresses HIV in the blood to undetectable levels, many people still experience ongoing inflammation and immune activation, and the virus can still persist in long-lived reservoirs. The FOA is aimed at studies that dig into the underlying molecular and cellular mechanisms driving these effects during suppressive ART, with a particular emphasis on how HIV proteins and/or HIV nucleic acids (such as viral RNA or DNA species that may still be produced or sensed despite suppression) can continue to stimulate inflammatory pathways, keep the immune system activated, and support HIV persistence. The overall goal is to move beyond describing that inflammation exists and instead define exactly how continued HIV expression or HIV-derived products are detected by the host, what signaling cascades are triggered, and how those pathways connect to clinical consequences and reservoir maintenance.

A central theme of the announcement is mechanistic clarity. Applicants are encouraged to identify which HIV gene products or nucleic acid forms are responsible, where in the body and in which cell types they act, and which host sensors and downstream pathways (for example, innate immune sensing and inflammatory signaling networks) translate residual HIV expression into immune activation. This includes work that can distinguish direct effects of HIV-derived molecules from indirect effects mediated by tissue damage, microbial translocation, co-infections, or other inflammatory drivers that may coexist during treated infection. The FOA is also interested in how these inflammatory and immune activation pathways feed back into HIV persistence, such as by maintaining survival or proliferation of infected cells, altering tissue microenvironments, or shaping immune responses in ways that allow reservoirs to remain stable.

In addition to defining mechanisms, the FOA explicitly encourages developing novel therapeutic strategies to mitigate or eliminate the effects of continued HIV expression during viral suppression. In practice, that means proposals can include preclinical or translational approaches that test interventions designed to interrupt the relevant sensing pathways, block key inflammatory mediators, reduce or neutralize the HIV-derived triggers, or otherwise limit the downstream immune activation that persists on ART. The emphasis is on strategies grounded in mechanistic understanding rather than broadly anti-inflammatory approaches without a clear link to HIV-derived drivers. Because the opportunity is labeled "Clinical Trial Not Allowed," the supported work is not intended to be an NIH-defined clinical trial; it is oriented toward mechanistic and therapeutic development research that stops short of interventional clinical trial designs.

From an administrative standpoint, this is a discretionary grant mechanism using the NIH R01 activity code, with the National Institutes of Health as the funding agency. The activity category is Health, and the CFDA number listed is 93.855. The original application due date shown is 2023-08-02, and the FOA was created on 2023-03-24. An award ceiling and expected number of awards are not provided in the source data excerpt, which typically means applicants need to consult the full FOA for budget expectations, scope guidance, and any institute-specific preferences.

Eligibility is broad and includes many standard applicant types such as state and local governments, public and private institutions of higher education, nonprofit organizations (with or without 501(c)(3) status), small businesses, and for-profit entities other than small businesses. It also includes Native American tribal governments (federally recognized) and tribal organizations (other than federally recognized tribal governments), as well as public housing authorities/Indian housing authorities. The announcement specifically highlights additional eligible applicants that NIH wants to encourage, including Alaska Native and Native Hawaiian Serving Institutions, Asian American Native American Pacific Islander Serving Institutions (AANAPISIs), 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, regional organizations, and non-U.S. entities (foreign organizations). This mix signals an intent to support a wide range of scientific teams and institutional settings, including groups positioned to connect mechanistic research to diverse populations and real-world HIV care contexts.

In short, the opportunity is designed for investigators who can rigorously explain why inflammation and immune activation persist during otherwise successful ART, identify the HIV-derived molecular triggers and host pathways responsible, clarify how those processes intersect with reservoir biology and persistence, and translate those insights into clearly justified therapeutic concepts that could ultimately reduce immune activation or weaken HIV persistence without running an NIH-defined clinical trial under this specific FOA.

• The National Institutes of Health in the health sector is offering a public funding opportunity titled "Defining Mechanisms of HIV Induced Inflammation and Immune Activation During Suppressive Antiretroviral Therapy (ART) (R01 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): 93.855.
• This funding opportunity was created on 2023-03-24.
• Applicants must submit their applications by 2023-08-02. (Agency may still review applications by suitable applicants for the remaining/unused allocated funding in 2026.)
• 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 AI 23 018

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