Exploiting in vivo or in situ imaging approaches to understand HIV-relevant processes in the context of substance use disorders (R61/R33 Clinical Trials Optional) | RFA DA 21 005

FAQs: NIH Discretionary Grant Opportunity RFA-DA-21-005 (Imaging, HIV/SIV, and Substance Use Disorders)

1) What is the main goal of this NIH funding opportunity (RFA-DA-21-005)?

This opportunity supports imaging-based research designed to clarify how HIV (and the simian model virus, SIV) behaves in the body, specifically in the real-world context of substance use disorders (SUD). The emphasis is on using advanced imaging to directly observe where virus persists, how infection and treatment affect tissues over time, and how SUD or SUD treatments may interact with HIV disease biology.

2) What kinds of imaging work does the program support?

Projects may either (a) further develop advanced in vivo (inside a living organism) or in situ (within intact tissues) imaging methods, or (b) apply already-emerging imaging approaches in new ways to answer HIV-relevant questions that standard sampling (such as blood draws alone) cannot resolve well.

3) Why is imaging emphasized instead of relying only on standard sampling?

The program is aimed at producing direct, anatomically grounded evidence about infection and treatment effects. Imaging can help researchers observe spatially localized and temporally dynamic processes (for example, within specific tissue regions or over treatment timelines) that may not be inferable from blood tests alone.

4) What scientific topics are especially encouraged?

A major emphasis is understanding HIV/SIV infection dynamics and the persistence of latent reservoirs (pockets of virus that remain even when antiretroviral therapy suppresses virus in the blood). The opportunity also encourages work on downstream pathogenic consequences of infection, such as inflammation, tissue damage, or neurological impacts, and on measuring or visualizing the effects of therapies targeting HIV/SIV or substance use disorders.

5) What are HIV/SIV latent reservoirs in the context of this announcement?

Latent reservoirs are areas or compartments in the body where virus can persist even when standard antiretroviral therapy has suppressed detectable virus levels in the blood. The program supports imaging approaches that can help identify, localize, and characterize these reservoirs and their dynamics over time.

6) How does substance use disorder (SUD) fit into the research focus?

The opportunity explicitly focuses on HIV/SIV biology in the context of SUD, including how SUD or SUD treatments may interact with HIV disease mechanisms, HIV persistence, and treatment outcomes. It also notes that SUD-related effects can be especially relevant to the central nervous system and immune function.

7) Are projects expected to look at changes over time (longitudinally)?

The description supports temporally dynamic study designs, such as imaging before and after treatment initiation, during relapse cycles, or across stages of disease, to understand how infection and interventions affect tissues over time.

8) Are spatial or tissue-specific questions part of the intended scope?

Yes. The program highlights spatially localized processes, such as changes in specific regions of lymphoid tissue or particular brain structures, which may require imaging approaches to detect and interpret.

9) Which organisms or study populations are allowed: humans, animals, or both?

Applicants may propose studies in nonhuman primates or in humans.

10) Which tissues or compartments are explicitly mentioned as areas of interest?

The opportunity explicitly includes blood, lymphoid tissues, and brain as tissues/compartments of interest.

11) What types of signals or processes might imaging track in these studies?

The opportunity notes that imaging and related technologies can include modalities that track cells, virus-associated signals, inflammatory processes, or drug distribution and activity, with the goal of making tissue- and anatomy-based observations.

12) Does the opportunity support imaging of treatment effects?

Yes. The program encourages measuring or visualizing the effects of therapies, whether those therapies target HIV/SIV itself or address substance use disorders.

13) What is the funding mechanism used for this opportunity?

The funding mechanism is the R61/R33 phased innovation award.

14) What does the R61/R33 phased innovation structure mean for applicants?

It is a milestone-driven structure with an early phase (R61) focused on feasibility, optimization, or proof-of-concept, followed by a second phase (R33) intended for expanded development and application once early milestones are met. This is presented as a good fit for imaging technology work because methods often require validation and performance demonstrations before broader deployment.

15) Are clinical trials required under this announcement?

Clinical trials are listed as optional.

16) Who administers this grant opportunity?

The opportunity is administered by the National Institutes of Health (NIH).

17) What is the CFDA number associated with this opportunity?

The CFDA number listed is 93.279.

18) What type of funding instrument is used?

The funding instrument is a grant.

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

The creation date listed is March 24, 2020, and the original closing date listed is July 9, 2021.

20) Is the award ceiling or the expected number of awards provided?

No. The provided source data does not specify an award ceiling or the expected number of awards.

21) What organizations are eligible to apply?

Eligibility is broad and includes: U.S. state, county, city/township governments; special district governments; independent school districts; public housing authorities/Indian housing authorities; public and state-controlled institutions of higher education; private institutions of higher education; nonprofits (501(c)(3) and non-501(c)(3)); for-profit organizations (other than small businesses); and small businesses.

22) Are faith-based, community-based, or community-relevant organizations eligible?

Yes. Faith-based or community-based organizations are explicitly highlighted among eligible categories.

23) Are tribal entities and minority-serving institutions included in the eligibility list?

Yes. The announcement highlights eligibility for a range of institutions and entities, including Historically Black Colleges and Universities (HBCUs), Hispanic-serving Institutions, Tribally Controlled Colleges and Universities (TCCUs), Alaska Native and Native Hawaiian Serving Institutions, Asian American Native American Pacific Islander Serving Institutions (AANAPISI), and tribal governments that are not federally recognized.

24) Are U.S. territories or non-U.S. organizations eligible to apply?

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

25) Why does the opportunity emphasize imaging in blood, lymphoid tissues, and brain?

The opportunity notes that HIV reservoirs and immune interactions can differ substantially across compartments, and that SUD-related effects are often especially relevant to the central nervous system and immune function. Imaging in these tissues can provide insight into compartment-specific persistence and pathology.