August 5, 2022
National Institute of Allergy and Infectious Diseases (NIAID)
National Institute of Mental Health (NIMH)
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.
Under this NOSI, clinical trials are not allowed, but the use of samples from clinical trials supported by other funding mechanisms is encouraged. Studies in animal models, using HIV, SIV, or SHIV, are included in the scope. Therapeutic interventions should be evaluated in an in vitro cell-based model prior to in vivo studies.
Examples of basic research activities include but are not limited to:
Examples of targeted interventions activities but are not limited to:
Examples of strategies include but are not limited to:
For applications proposing the use of novel interventions, the participation of an intellectually contributing private sector/industry partner as a significant collaborator in the application is strongly encouraged.
Applications will be considered non-responsive to this NOSI if the applications:
Application and Submission Information
Applicants must select the IC and associated FOA to use for submission of an application in response to the NOSI. The selection must align with the IC requirements listed in order to be considered responsive to that FOA. Non-responsive applications will be withdrawn from consideration for this initiative. In addition, applicants using NIH Parent announcements (listed below) will be assigned to those ICs on this NOSI that have indicated those FOAs are acceptable and based on usual application-IC assignment practices.
Submit applications for this initiative using one of the following funding opportunity announcements (FOAs) or any reissues of these announcement through the expiration date of this notice.
All instructions in the SF424 (R&R) Application Guide and the funding opportunity announcement used for submission must be followed, with the following additions:
Although NIMH is not listed as a Participating Organization in all the FOAs listed above, applications for this initiative will be accepted.
Applications nonresponsive to terms of this NOSI will be withdrawn from consideration for this initiative.