Through novel approaches, researchers could find ways to diminish HIV reservoir formation at the time of combination antiretroviral therapy (cART) initiation when HIV antigen is still expressed on CD4+ cells and can be targeted for cure strategies. Consider proposing a new research project if you are capable of exploring novel strategies in furtherance of this approach.
NIAID will accept applications through Opportunities for HIV Cure Strategies at the Time of ART Initiation (R01, Clinical Trial Not Allowed) and Opportunities for HIV Cure Strategies at the Time of ART Initiation (R21, Clinical Trial Not Allowed). These companion notices of funding opportunities (NOFOs) replace a related notice of special interest, NOT-AI-22-072, which is now expired.
Scientific Objectives
Through this initiative, NIAID will support basic research into novel mechanisms that contribute to intervention-mediated viral control and reductions in reservoir size as well as experimental, innovative targeted intervention activities. These strategies must take place close to the time of cART initiation, before viral loads are completely suppressed, or after an analytical treatment interruption to potentially enhance the HIV-specific immune response or reduce reservoir size.
We hope also to gain a deeper understanding of the decay dynamics of virus-infected cell subsets following cART initiation. Doing so necessitates longitudinal studies of the viral reservoir early in active infection and immediately after cART initiation.
Examples of appropriate basic research studies include:
- Research to detect, quantify, and characterize HIV/SIV reservoir seeding in different cell types and tissues at various time points near ART initiation or during therapeutic intervention prior to cART initiation. You could compare different HIV subtypes, acute versus chronic infection, humans versus animal models, and different ages and sexes of individuals.
- Analyzing the HIV reservoir dynamics, decay rates of various cell types, clonal proliferation, proportion of intact versus defective HIV/SIV, distribution of active versus latent reservoirs, and reactivation potential of latent HIV/SIV at or near the time of cART initiation.
- Comparing reservoir or immunologic changes in response to strategies delivered at different time points in relation to cART initiation or in place of conventional cART, including visualization studies.
Example targeted intervention activities include:
- Identifying experimental cure/remission strategies in cell models ex vivo or animal models in vivo prior to or at the initiation of cART that contribute to a reduction in reservoir size, an increased decay rate of the reservoir, or post-treatment control of viral rebound. Successful strategies could be later employed during an analytical treatment interruption.
- Identifying short-term strategies in preclinical models, instead of or in combination with cART, that could differ from life-long cART in enabling durable control of rebound with one-time or intermittent use.
Within those activities, the strategies under investigation could be:
- Strategies to eliminate HIV-infected cells
- Inhibiting latency establishment before or at the start of cART
- Preventing clonal expansion of reservoir cells
- Preventing HIV dissemination and approaches to block HIV trafficking
- Limiting reservoir seeding in sanctuary sites (e.g., B cell follicles)
- Optimizing and boosting the anti-HIV immune response
Your project may propose the use of animal models. You may also use existing human clinical samples. Therapeutic strategies should be evaluated in an in vitro primary cell-based model prior to commencing in vivo studies. Early HIV/SIV cure strategies without cART that demonstrated a clear antiviral effect in previous studies are allowed.
If you propose a novel product development path, seek a private sector or industry partner to participate as a significant collaborator. Private sector partners should be actively involved in the study design and performance.
Clinical trials are not allowed. Nor are strategies that are started more than 1 month after initiation of cART; nor cART intensification strategies alone without inclusion of non-cART-based strategies; nor FDA-approved drugs as “cure interventions” without a rationale for disrupting an HIV-associated pathway and without a mechanistic approach.
Companion NOFOs
This initiative leverages both an R01 and R21 NOFO. The former will support more developed (up to 5 years) research projects while the latter is ideal for shorter term (up to 2 years) developmental or exploratory activities.
There is no budget cap for R01 applications, although your request must reflect the actual needs of your project. Should your budget request exceed $500,000 in direct costs in any 1 year, you will need to request our prior approval before submitting your application, as outlined in our Big Grants policy. For an R21 application, your budget cannot exceed $275,000 over 2 years, with no more than $200,000 requested in any single year.
The two NOFOs share submission deadlines, matching NIH’s standard due dates for AIDS and AIDS-Related Applications, the next of which is January 7, 2024.
Scientific/Research Contact
If you have any questions, reach out to NIAID’s Dr. Brigitte Sanders at sandersbe@niaid.nih.gov or 240-627-3209.