The NIH's "Novel Preclinical Models of NeuroHIV in the cART Era" funding opportunity (R61/R33, Clinical Trial Not Allowed) seeks to develop and validate small animal and human cellular models that replicate the complex interactions between the central nervous system (CNS) and the immune system in people with HIV (PWH) under antiretroviral therapy (ART) suppression. The initiative is driven by the need to improve NeuroHIV models that accurately reflect CNS dysfunction and residual viral infection in the ART era, where the virus is suppressed but not eliminated.

The program emphasizes creating preclinical models that incorporate various CNS cell types and peripheral immune cells. These models should replicate the conditions of chronic HIV infection with ART suppression, moving beyond the traditional focus on acute viral infection. Proposed models may include human cells, but this is not mandatory as long as the model supports natural HIV infection with a replication-competent virus under ART suppression. The initiative will not fund the development of non-human primate models.

The program uses a phased R61/R33 award structure. The R61 phase supports the development and validation of the model, focusing on demonstrating the presence, functionality, and infection of CNS cells. The R33 phase expands into phenotyping the model in the context of ART, focusing on neurological outcomes, such as neuroinflammation, neurodegeneration, and BBB integrity, without behavioral studies as the primary focus.

Applicants must define milestones for transitioning from the R61 to the R33 phase and propose detailed collaboration with clinical NeuroHIV experts to ensure models accurately reflect the clinical reality of NeuroHIV in the ART era. The NIH expects applicants to share their models widely with the NeuroHIV research community. Intellectual property (IP) considerations related to model dissemination must be addressed, including letters of support from technology transfer offices if relevant.

Budgets are capped at $600,000 in direct costs per year. The project period is up to four years, with no more than two years for the R61 phase and three years for the R33 phase. Applicants should submit by December 2, 2024, for funding consideration.