Mechanistic Evaluation of Therapeutic Targets derived from Treatable Traits to Improve CNS Outcomes in People with HIV (R21/R33 Clinical Trial Not Allowed)

The National Institutes of Health, through the NIMH, NIDA, and NINDS, is soliciting applications for a phased R21/R33 research initiative titled Mechanistic Evaluation of Therapeutic Targets derived from Treatable Traits to Improve CNS Outcomes in People with HIV. This funding opportunity aims to identify modifiable mechanisms and therapeutic targets to address central nervous system complications associated with HIV. The research follows a two-phase approach: an initial Innovation Phase (R21) focused on identifying patient phenotypes and validating molecular mechanisms using in-vitro and in-vivo models, followed by a Confirmatory Phase (R33) to evaluate target engagement and intervention discovery. Funding is contingent upon NIH appropriations, with NIMH intending to commit 2.5 million dollars and both NINDS and NIDA committing 1 million dollars each for fiscal years 2027 and 2028. Direct costs for the R21 phase are capped at 275,000 dollars for two years, while the R33 phase allows up to 650,000 dollars per year for up to three years. Applications are evaluated via a peer review system based on significance, innovation, approach, investigator expertise, and environment. Eligible applicants include small businesses and other for-profit organizations, who must maintain active SAM registration and comply with federal regulations regarding human subjects protection, vertebrate animal use, and cybersecurity incident reporting.