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

FAQs: NIH Grant Opportunity RFA AI 23 018 (R01)

What is this funding opportunity?

This is a National Institutes of Health (NIH) research funding announcement, RFA AI 23 018, using the R01 activity code. It supports research focused on understanding and addressing persistent inflammation and immune activation in people with HIV who are on suppressive antiretroviral therapy (ART).

What problem is the FOA trying to solve?

The FOA targets a persistent issue in HIV medicine: even when ART suppresses HIV in the blood to undetectable levels, many individuals still experience ongoing inflammation and immune activation, and HIV can persist in long-lived reservoirs. The goal is to explain why that happens and how it connects to HIV persistence and clinical consequences.

What is the main scientific focus of the announcement?

The central focus is mechanistic research that explains, at a molecular and cellular level, how HIV-derived products (such as HIV proteins and/or HIV nucleic acids like viral RNA or DNA species) can still be produced, sensed, and drive inflammatory pathways during suppressive ART.

What does "mechanistic clarity" mean in this FOA?

Mechanistic clarity means going beyond describing that inflammation exists and instead defining exactly which HIV-derived molecules are involved, how the host detects them, which signaling cascades are triggered, where in the body the interactions occur, and how these processes link to immune activation, clinical outcomes, and reservoir maintenance.

What kinds of HIV-derived triggers are emphasized?

The FOA places particular emphasis on HIV proteins and HIV nucleic acids (for example, viral RNA or DNA species) that may still be generated or sensed despite blood viral suppression, and that may continue to stimulate inflammatory and innate immune pathways.

Does the FOA specify where and in which cells these mechanisms should be studied?

Yes. Applicants are encouraged to identify where in the body these processes occur and which cell types are involved. The intent is to pinpoint the relevant tissues, compartments, and cellular targets involved in ongoing sensing and signaling during suppressive ART.

What host processes or pathways are of interest?

The FOA is interested in how the host detects residual HIV expression or HIV-derived products and which downstream signaling pathways are activated. The description specifically points to innate immune sensing and inflammatory signaling networks as examples of the types of pathways applicants may investigate.

Is the FOA interested in distinguishing direct HIV effects from other causes of inflammation?

Yes. The announcement highlights the importance of distinguishing direct effects of HIV-derived molecules from indirect effects driven by other inflammatory contributors that may coexist during treated infection, such as tissue damage, microbial translocation, co-infections, or other inflammatory drivers.

How does the FOA connect inflammation to HIV reservoir persistence?

The FOA is explicitly interested in feedback links between inflammatory/immune activation pathways and HIV persistence. Examples described include mechanisms by which these pathways might maintain survival or proliferation of infected cells, alter tissue microenvironments, or shape immune responses in ways that allow reservoirs to remain stable.

Is developing therapies allowed or encouraged under this FOA?

Yes. In addition to defining mechanisms, the FOA explicitly encourages the development of novel therapeutic strategies to mitigate or eliminate the effects of continued HIV expression during viral suppression, as long as the strategies are grounded in a clear mechanistic understanding.

What kinds of therapeutic strategies fit the FOA's intent?

Based on the description, suitable strategies could include approaches that interrupt relevant sensing pathways, block key inflammatory mediators, reduce or neutralize HIV-derived triggers, or otherwise limit downstream immune activation that persists on ART. The common thread is that the intervention concept should be tied to a defined HIV-derived driver and a defined host pathway.

Are broadly anti-inflammatory approaches appropriate?

The FOA emphasizes strategies grounded in mechanistic understanding rather than broadly anti-inflammatory approaches that do not have a clear link to HIV-derived drivers. Projects are expected to connect the intervention rationale to specific HIV-derived triggers and the host pathways they activate.

Are clinical trials allowed?

No. The opportunity is labeled "Clinical Trial Not Allowed." Supported work is oriented toward mechanistic and therapeutic development research that stops short of an NIH-defined interventional clinical trial design under this FOA.

What grant mechanism is used?

This opportunity uses the NIH R01 activity code and is described as a discretionary grant mechanism.

Who is the funding agency?

The funding agency is the National Institutes of Health (NIH).

What is the activity category and CFDA number?

The activity category is Health, and the CFDA number listed is 93.855.

When was the FOA created and what is the application due date provided here?

The FOA was created on 2023-03-24, and the original application due date shown in the provided information is 2023-08-02.

Does the provided information include an award ceiling or number of expected awards?

No. The excerpt provided does not list an award ceiling or the expected number of awards. In situations like this, applicants are typically expected to consult the full FOA for budget expectations, scope guidance, and any institute-specific preferences.

What types of organizations are eligible to apply?

Eligibility is broad and includes 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), tribal organizations (other than federally recognized tribal governments), and public housing authorities/Indian housing authorities.

Are non-U.S. (foreign) organizations eligible?

Yes. The eligibility list explicitly includes non-U.S. entities (foreign organizations).

Which additional institution types does NIH specifically encourage to apply?

The announcement specifically highlights and encourages applications from Alaska Native and Native Hawaiian 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, and regional organizations, in addition to non-U.S. entities.

What kinds of research teams or settings does this eligibility mix suggest?

Based on the description, the eligibility mix suggests NIH intends 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.

What is the overall goal of projects under this FOA?

The overall goal is to 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 (without conducting an NIH-defined clinical trial under this FOA).