Opportunity Information: Apply for RFA DA 24 003

The funding opportunity "Targeting Inflammasomes in Substance Abuse and HIV (R01 Clinical Trial Not Allowed)" (RFA-DA-24-003) is a National Institutes of Health (NIH) discretionary grant that supports research aimed at clarifying how inflammasomes contribute to brain and nervous system damage linked to acute or chronic drug exposure in the context of HIV infection. The central scientific goal is to better define the biological mechanisms by which inflammasome-driven immune responses influence neuropathology when substance use and HIV-related processes intersect. Because this is an R01 mechanism, it is intended to back substantial, hypothesis-driven projects that can meaningfully advance understanding of these pathways, but it explicitly does not allow clinical trials.

A major emphasis of the announcement is the role of inflammasomes in virus- and drug-induced immune activation, particularly as it relates to neuroinflammation and broader immune dysregulation. Inflammasomes are immune signaling complexes that can detect cellular stress or infection and trigger inflammatory cascades; when they are excessively activated or improperly regulated, they can amplify inflammatory damage. In the setting of HIV and substance use, this matters because both can independently alter immune function and central nervous system (CNS) biology, and together they may intensify inflammatory signaling in ways that accelerate neurological complications or worsen disease trajectories. The opportunity is framed around generating clearer evidence about which inflammasome pathways are involved, how they are engaged by different drugs or patterns of exposure, and how HIV infection modifies these responses in the CNS.

Another key objective is to help identify molecular markers and CNS immune cell types associated with HIV-1 infection and disease progression among people with substance use involvement. In practical terms, the research encouraged here could lead to biomarkers that signal heightened inflammasome activation, indicate specific neuroimmune changes, or predict risk for neurological impairment. It also seeks to sharpen understanding of which CNS-resident or infiltrating immune cells (for example, microglia or other neuroimmune populations) are most relevant to inflammasome-driven pathology under these combined conditions.

The announcement also highlights translational potential: insights from mechanistic studies are expected to inform novel therapeutic strategies that either target inflammasome activation or promote its suppression, with the end goal of treating or preventing neuroinflammation and immune dysregulation tied to HIV and substance exposure. Rather than supporting clinical intervention trials, the FOA is oriented toward foundational and preclinical or non-trial human research that can map pathways, validate targets, and establish a rationale for future therapeutic development.

Eligibility is broad and includes many types of U.S. domestic organizations, such as state and local governments, public and private institutions of higher education, nonprofit organizations (with or without 501(c)(3) status), for-profit organizations (other than small businesses), and small businesses, as well as certain housing authorities and tribal entities. It also explicitly welcomes applications from a range of mission-driven and capacity-building institutions and groups, including Alaska Native and Native Hawaiian 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, regional organizations, U.S. territories or possessions, and non-domestic (non-U.S.) entities (foreign organizations). This inclusive applicant list signals NIH interest in drawing on diverse research settings and populations, which is particularly relevant given the public health overlap between HIV, substance use, and neurological outcomes.

Key administrative details from the source data include: the agency is NIH; the assistance listing is CFDA 93.279; the opportunity category is discretionary; the funding instrument is a grant; and the original closing date listed is 2023-03-16, with a creation date of 2022-11-03. The award ceiling and expected number of awards are not specified in the provided data.

  • The National Institutes of Health in the education, health sector is offering a public funding opportunity titled "Targeting Inflammasomes in Substance Abuse and HIV (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): 93.279.
  • This funding opportunity was created on 2022-11-03.
  • Applicants must submit their applications by 2023-03-16. (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.
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Frequently Asked Questions (FAQs)

What is the title and number of this funding opportunity?

The opportunity is titled "Targeting Inflammasomes in Substance Abuse and HIV (R01 Clinical Trial Not Allowed)" and the funding opportunity number is RFA-DA-24-003.

Which agency is offering this grant?

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

What type of funding mechanism is being used?

This opportunity uses the R01 grant mechanism. It is intended to support substantial, hypothesis-driven research projects.

Are clinical trials allowed under this FOA?

No. The opportunity explicitly states Clinical Trial Not Allowed, meaning applications proposing clinical trials are not permitted under this announcement.

What is the overall scientific focus of the opportunity?

The central focus is to clarify how inflammasomes contribute to brain and nervous system damage linked to acute or chronic drug exposure in the context of HIV infection. The goal is to define biological mechanisms where substance use and HIV-related processes intersect to influence neuropathology.

What are inflammasomes, as described in the opportunity?

Inflammasomes are described as immune signaling complexes that can detect cellular stress or infection and trigger inflammatory cascades. When excessively activated or improperly regulated, they can amplify inflammatory damage.

Why is the HIV and substance use intersection emphasized?

The opportunity highlights that HIV and substance use can each independently alter immune function and central nervous system (CNS) biology. Together, they may intensify inflammatory signaling and potentially accelerate neurological complications or worsen disease trajectories.

What kinds of scientific questions does NIH want researchers to address?

Based on the description provided, NIH is seeking research that generates clearer evidence about:

  • Which inflammasome pathways are involved in HIV- and drug-associated neuroimmune effects
  • How different drugs or patterns of exposure engage those pathways
  • How HIV infection modifies inflammasome-driven responses in the CNS
  • How inflammasome-driven immune responses influence neuropathology when HIV and substance use overlap

Is neuroinflammation a major theme of the FOA?

Yes. A major emphasis is the role of inflammasomes in virus- and drug-induced immune activation, particularly as it relates to neuroinflammation and broader immune dysregulation.

Does the FOA encourage biomarker or molecular marker research?

Yes. A key objective is to help identify molecular markers associated with HIV-1 infection and disease progression among people with substance use involvement. The FOA frames this as potentially enabling biomarkers that signal heightened inflammasome activation, indicate specific neuroimmune changes, or predict risk for neurological impairment.

Does the FOA specify interest in particular CNS immune cell types?

Yes. The opportunity calls for sharper understanding of which CNS-resident or infiltrating immune cells are most relevant to inflammasome-driven pathology under combined HIV and substance exposure conditions, with microglia mentioned as an example.

Is the FOA focused on basic science, translational work, or both?

It includes a strong mechanistic foundation with explicit translational intent. The FOA emphasizes that insights from mechanistic studies are expected to inform therapeutic strategies that target inflammasome activation or promote its suppression, while still remaining non-clinical-trial in scope.

Does this opportunity support development of therapies?

The announcement highlights translational potential and expects mechanistic insights to inform novel therapeutic strategies aimed at treating or preventing neuroinflammation and immune dysregulation tied to HIV and substance exposure. However, it does not support clinical intervention trials under this FOA.

What kinds of studies are most aligned with the FOA, given the clinical trial restriction?

As described, the FOA is oriented toward foundational and mechanistic research, including preclinical or non-trial human research that can map pathways, validate targets, and establish a rationale for future therapeutic development (without proposing a clinical trial).

Who is eligible to apply?

Eligibility is broad and includes many types of organizations, including:

  • State and local governments
  • Public and private institutions of higher education
  • Nonprofit organizations (with or without 501(c)(3) status)
  • For-profit organizations (other than small businesses)
  • Small businesses
  • Certain housing authorities
  • Tribal entities
  • Eligible federal agencies
  • Regional organizations
  • U.S. territories or possessions
  • Non-domestic (non-U.S.) entities (foreign organizations)

Does the FOA encourage applications from specific institution types?

Yes. The opportunity explicitly welcomes applications from a range of mission-driven and capacity-building institutions and groups, including:

  • Alaska Native and Native Hawaiian Serving Institutions
  • AANAPISISs
  • Hispanic-serving Institutions
  • Historically Black Colleges and Universities (HBCUs)
  • Tribally Controlled Colleges and Universities (TCCUs)
  • Faith-based or community-based organizations

Are foreign (non-U.S.) organizations allowed to apply?

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

What is the Assistance Listing (CFDA) number for this opportunity?

The Assistance Listing (CFDA) number provided is 93.279.

What is the funding instrument and opportunity category?

The funding instrument is a grant, and the opportunity category is discretionary.

When was the opportunity created, and what closing date is listed?

The creation date listed is 2022-11-03, and the original closing date listed is 2023-03-16.

Is the award ceiling provided?

No. The award ceiling is not specified in the information provided.

Is the expected number of awards provided?

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

What is the intended impact of research funded by this FOA?

The stated intent is to advance understanding of inflammasome-driven immune mechanisms at the intersection of HIV infection and substance exposure, particularly in relation to CNS injury, neuroinflammation, and immune dysregulation. The FOA also points toward informing future therapeutic strategies by identifying pathways, targets, biomarkers, and relevant CNS immune cell types.

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