Exploratory studies to investigate mechanisms of HIV infection, replication, latency, and/or pathogenesis in the context of substance use disorders (R61/R33 - Clinical Trial Not Allowed) | RFA DA 24 002

Frequently Asked Questions (FAQs)

What is this funding opportunity?

This is an NIH funding opportunity (RFA-DA-24-002) supporting exploratory research to understand the biological mechanisms of HIV specifically in the context of substance use disorders (SUDs).

What is the main scientific focus of the program?

The program prioritizes mechanistic research that explains how and why HIV behaves the way it does when substance use is part of the clinical and biological picture. The emphasis is on biological mechanisms tied to HIV infection establishment, replication, persistence in latent reservoirs, and disease processes over time, including HIV-associated neurocognitive disorders (HAND).

What kinds of research questions are encouraged?

Projects are expected to pursue mechanistic "how and why" questions, such as how substance use or SUD-related factors influence immune function, inflammation, tissue microenvironments, viral transcription, viral persistence, reservoir establishment or maintenance, comorbid infections, and neurobiological or neuropathological processes relevant to HAND.

Is this opportunity meant for service delivery or implementation projects?

No. The description emphasizes mechanistic biology rather than service delivery, broad epidemiology, or intervention efficacy. Projects centered on delivering services, implementing programs, or evaluating real-world service models are not the focus of this solicitation.

Are broad epidemiology studies a fit for this opportunity?

The opportunity description indicates that broad epidemiology is not the main target. Applicants are expected to connect substance use and HIV outcomes to specific biological mechanisms rather than focusing primarily on population-level patterns without mechanistic investigation.

Are clinical trials allowed under this announcement?

No. The opportunity explicitly states that clinical trials are not allowed, indicating the work should remain non-trial, mechanistic research rather than clinical testing of an intervention.

What NIH funding mechanism is being used?

The solicitation uses the NIH R61/R33 phased innovation mechanism, designed to support early-stage exploratory work with a structured pathway to expand into a second phase if predefined milestones are met.

How does the R61/R33 phased approach typically work?

The project is generally structured in two parts: an initial exploratory phase (R61) intended to establish feasibility or generate key proof-of-mechanism evidence, followed by a second phase (R33) that builds on successful results from the first phase.

What determines whether a project moves from the R61 phase to the R33 phase?

While the excerpt does not list specific milestone requirements, it indicates that progression is typically contingent on meeting objective, measurable go/no-go criteria established for the first phase.

What is the funding instrument and activity area?

This opportunity uses a discretionary, grant-based funding instrument under the Health and Education activity area, referenced as CFDA 93.279, and is administered by the National Institutes of Health.

What is the award ceiling?

The opportunity lists an award ceiling of $350,000. The excerpt notes this as an upper bound on available funding; whether this applies per year or per project period depends on the full announcement details.

When was the opportunity posted and what was the original closing date?

It was originally posted on 2022-11-15, with an original closing date of 2023-03-23.

How central does substance use need to be in the proposed research?

Substance use disorders are expected to be a central biological variable in the proposed work. Competitive projects will likely integrate specific substances or patterns of use and link them to concrete biological pathways that influence HIV outcomes.

Does the opportunity emphasize HIV persistence and latent reservoirs?

Yes. The program highlights mechanistic questions about how HIV persists in latent reservoirs, including how reservoirs are established or maintained, particularly in the context of substance use.

Is HIV-associated neurocognitive disorders (HAND) within scope?

Yes. HAND is explicitly mentioned as part of the disease processes of interest over time, with emphasis on neurobiological and neuropathological mechanisms that may be affected by substance use.

Can projects examine interactions between substance use and antiretroviral therapy (ART)?

Yes, if approached mechanistically and not as a clinical trial. The scope suggests interest in how substance use might alter responses to ART at a biological level (for example, effects on viral dynamics, immune activation, or cellular targets), as long as the work remains non-trial mechanistic research rather than testing an intervention in a clinical trial framework.

What types of applicants are eligible to apply?

Eligibility is broad and includes state, county, city/township, 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; non-federally recognized tribal organizations; public housing authorities/Indian housing authorities; nonprofits with or without 501(c)(3) status (excluding higher education institutions in those categories); for-profit organizations other than small businesses; and small businesses.

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

Yes. The opportunity explicitly highlights a range of additional eligible applicants and institutional categories NIH is welcoming, including Alaska Native and Native Hawaiian Serving Institutions, AANAPISIs, Hispanic-serving institutions, HBCUs, TCCUs, and faith-based or community-based organizations.

Are U.S. territories and federal agencies eligible?

Yes. The announcement indicates eligibility includes eligible federal agencies, regional organizations, and U.S. territories or possessions.

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

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

What distinguishes a competitive application under this opportunity?

Based on the description, competitive applications will likely (1) focus on mechanistic HIV biology, (2) clearly integrate substance use or SUD-related factors as a central variable, (3) connect those factors to specific biological pathways influencing HIV infection, replication, persistence, reservoirs, or disease progression (including HAND), and (4) fit the R61/R33 structure with clear, measurable milestones supporting a go/no-go transition between phases.

Is this opportunity intended for early-to-mid stage research?

Yes. It is described as a call for early-to-mid stage mechanistic HIV science with a phased structure designed to move from exploratory findings to a more developed research effort once milestones are met.