Elucidating Immunometabolic Responses to HIV Infection that Increase TB or HBV Risk (R01 Clinical Trial Not Allowed) | PAR 25 315

Frequently Asked Questions (FAQs)

What is the NIH funding opportunity PAR-25-315?

PAR-25-315 is an NIH Notice of Funding Opportunity (NOFO) titled "Elucidating Immunometabolic Responses to HIV Infection that Increase TB or HBV Risk (R01 Clinical Trial Not Allowed)." It supports R01 research projects that investigate how HIV-driven changes in immune function and cellular metabolism (immunometabolism) persist even when HIV is virally suppressed on combination antiretroviral therapy (cART), and how those changes may raise the risk of worse outcomes from tuberculosis (TB) or hepatitis B virus (HBV).

What is the main scientific problem this NOFO is trying to address?

The NOFO targets the gap between viral suppression and full immune recovery. Even when people living with HIV are doing well on cART and HIV is suppressed, lasting immunometabolic changes can remain. This opportunity focuses on clarifying how those persistent changes reshape immune responses in ways that increase susceptibility to, worsen control of, or worsen disease progression and recovery from co-infections that can persist over time, particularly Mycobacterium tuberculosis (Mtb) and HBV.

Which co-infections are emphasized under this opportunity?

The NOFO particularly emphasizes Mycobacterium tuberculosis (Mtb), which causes tuberculosis (TB), and hepatitis B virus (HBV). The aim is to understand how treated HIV-related immunometabolic alterations may contribute to increased TB or HBV risk and poorer outcomes.

What does "immunometabolic responses" mean in the context of this NOFO?

In this NOFO, immunometabolic responses refer to the ways immune cell function and immune regulation are shaped by cellular metabolism, including how immune cells are metabolically programmed, how they behave, and how they interact with other cells. The NOFO is interested in how HIV leaves lasting immunometabolic effects despite cART-mediated viral suppression, and how those effects influence vulnerability to TB or HBV.

What types of studies are encouraged?

This NOFO emphasizes mechanistic research that clarifies how HIV-associated immunometabolic changes affect immune cell regulation and behavior. Examples described in the opportunity include studies of metabolic programming of immune cells, cell-cell interactions that shape immune responses, and how immunometabolic changes influence responses to treatments relevant to TB or HBV. The overall direction is basic, translational, and mechanistic work that links immunometabolic states to functional immune outcomes.

What kinds of platforms or approaches might be used if clinical trials are not allowed?

While clinical trials are not allowed, the NOFO indicates research may involve human samples, ex vivo analyses, computational and systems biology approaches, animal models, and other experimental platforms. The key point is that projects should remain non-clinical-trial in the NIH sense, focusing on mechanistic insight rather than prospective interventional studies in humans designed to evaluate health-related outcomes.

Are clinical trials allowed under PAR-25-315?

No. The opportunity is explicitly labeled "Clinical Trial Not Allowed." Applicants should propose studies that do not meet NIH's definition of a clinical trial.

If clinical trials are not allowed, what does that generally mean for project design?

It generally means applicants should avoid prospective interventional studies in humans designed to evaluate health-related outcomes. The NOFO steers applicants toward mechanistic and translational study designs (for example, using human samples and ex vivo work, computational/systems biology, animal models, or other experimental platforms) that investigate underlying pathways and mechanisms rather than testing interventions in a clinical trial framework.

What is the grant mechanism for this opportunity?

The mechanism is an R01 research project grant. The opportunity supports R01 research projects aligned with the NOFO's scientific scope.

What is the overall goal or expected impact of the funded research?

The expected impact is a clearer map of immune-metabolic drivers of TB and HBV risk and disease progression in the context of treated HIV. By pinpointing specific metabolic and immune regulatory pathways that remain altered despite viral suppression, the work may set up future strategies for host-directed interventions, improved risk stratification, and better-tailored prevention and therapeutic approaches for TB or HBV in people living with HIV on cART.

What is the activity category and funding instrument?

The activity category is health research, and the funding instrument is a grant.

What is the CFDA number listed for this opportunity?

The CFDA number listed is 93.855.

Who is the sponsoring agency?

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

When was this opportunity created?

The opportunity was created on 2024-12-18.

What is the closing date listed for this opportunity?

The original closing date listed is 2028-01-07.

Is an award ceiling specified?

No award ceiling is specified in the information provided.

Is the expected number of awards listed?

No. The expected number of awards is not listed in the information provided.

What types of organizations are eligible to apply?

Eligibility is broad. Eligible applicants include: state, county, city, and 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; tribal organizations not federally recognized; public housing authorities/Indian housing authorities; nonprofits with or without 501(c)(3) status; for-profit organizations other than small businesses; small businesses; and other entities.

Are minority-serving institutions and community-based organizations eligible?

Yes. The NOFO highlights additional eligible categories including Alaska Native and Native Hawaiian Serving Institutions, AANAPISIs, Hispanic-serving Institutions, HBCUs, TCCUs, and faith-based or community-based organizations.

Are non-U.S. organizations eligible to apply?

Yes. The eligibility list includes non-domestic (non-U.S.) entities and foreign organizations, as well as regional organizations, and U.S. territories or possessions.

Are federal agencies eligible to apply?

Yes. The NOFO lists eligible federal agencies among the eligible applicant categories.

Does this opportunity focus on people living with HIV who are on cART and virally suppressed?

Yes. The scientific focus is on a problem observed in people living with HIV who are doing well on combination antiretroviral therapy (cART), where HIV is virally suppressed but lasting immunometabolic and immune functional alterations may persist.

What kinds of immune biology questions are specifically called out?

The NOFO calls out mechanistic questions such as how immune cells are metabolically programmed, how immune cells communicate via cell-cell interactions, and how HIV-associated immunometabolic changes influence immune regulation, immune behavior, and responses to treatments relevant to TB or HBV.

What does the NOFO say about linking metabolism to immune outcomes?

The NOFO emphasizes connecting immunometabolic states to functional immune outcomes in order to explain why some individuals with suppressed HIV still experience increased susceptibility to co-infections, worse control of TB or HBV, more severe disease, or poorer recovery trajectories.

How is this opportunity categorized in terms of funding type?

The opportunity is categorized as discretionary and uses the grant funding instrument.