Notice of Special Interest (NOSI): Opportunities for HIV Cure Interventions at the Time of ART Initiation

Funding Agency:
National Institutes of Health

This Notice of Special Interest (NOSI) serves to identify new opportunities for cure interventions administered during active HIV infection at or near the start of antiretroviral therapy (ART) or as a potential replacement for conventional ART, with the ultimate goal of achieving a sustained ART-free HIV remission.

The initiation of ART within the first few weeks of HIV infection has been associated with the development of a smaller latent reservoir, reduced viral diversity, preservation of innate as well as T and B cell immune responses, and higher rates of post treatment control. Additional interventions, in combination with the start of ART, may potentially accelerate viral decay, limit reservoir seeding, and induce a vaccinal effect that, in combination, may induce HIV remission. Currently, HIV cure approaches are focused almost exclusively on interventions administered during complete viral suppression on ART. Recent scientific evidence suggests that much of the reservoir is seeded at the time of ART initiation. It is thought that ART alters the host environment in a way that promotes the formation of most of the long-lived latent HIV reservoir. Therefore, there is an opportunity to explore novel strategies designed to limit the establishment of the HIV reservoir around the time of ART initiation. In more translational studies, some early interventions using broadly neutralizing antibodies in the absence of ART have led to sustained remission in non-human primates (NHP). Therefore, opportunities also exist to intervene before complete ART-mediated viral suppression, when HIV antigen is stimulating the immune response, to improve clinical outcomes toward an HIV cure.

The scientific objective of this NOSI is to support projects to explore HIV cure approaches administered during active HIV/SHIV/SIV infection, prior to or around the time of ART initiation, before viral loads are completely suppressed, to potentially enhance the ongoing immune response and prevent additional reservoir seeding. A better understanding of the decay dynamics of various virus-infected cell subsets following ART initiation is also needed. Therefore, longitudinal studies of the viral reservoir early in active infection and immediately after ART initiation, will be supported to inform the development of new cure strategies. Additionally, basic research into the unique mechanisms that contribute to intervention-mediated viral control and the prevention of reservoir seeding will be important. The curative interventions studied should be experimental, innovative, and not yet approved by the FDA for an HIV indication.

This notice applies to due dates on or after January 7, 2023 and subsequent receipt dates through September 7, 2025

Expiration Date:

New Date - August 22, 2022 (Original Date: September 08, 2025) per issuance of NOT-AI-22-066


Agency Website

Amount Description


Funding Type





Medical - Basic Science
Medical - Clinical Science
Medical - Translational

External Deadline

August 22, 2022