The purpose of this Notice of Funding Opportunity (NOFO) is to identify cure strategies suitable for administration at the start of combination antiretroviral therapy (cART) and/or at cART restart after an analytical treatment interruption (ATI), with the ultimate goal of achieving sustained treatment-free remission. The scientific objective of this NOFO is to explore HIV cure strategies administered during ongoing HIV/SHIV/SIV infection, close to the time of cART initiation, before viral loads are completely suppressed, or after an analytical treatment interruption (ATI) to potentially enhance the HIV-specific immune response and/or reduce reservoir size. In addition to early cure interventions, a deeper understanding of the decay dynamics of virus-infected cell subsets following cART initiation is also needed. Therefore, longitudinal studies of the viral reservoir early in active infection and immediately after cART initiation will also be supported to inform the development of new cure strategies.

This NOFO aims to support basic research and targeted intervention activities. Basic research into novel mechanisms that contribute to intervention-mediated viral control and reductions in reservoir size will be important. The targeted interventions studied should be experimental, innovative, and not yet approved by the FDA or a foreign regulatory agency for an HIV indication.

Although clinical trials are not allowed, the use of samples from clinical trials supported by other funding mechanisms is encouraged. Besides human samples, studies in animal models, using HIV, SIV, or SHIV, are allowed. Preferentially, therapeutic strategies should be evaluated in an in vitro primary cell-based model prior to commencing in vivo studies. Early HIV/SIV interventions without cART that have demonstrated a clear antiviral effect in previous studies are also allowed.

Early HIV/SIV cure strategies without cART that demonstrated a clear antiviral effect in previous studies are allowed.