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

This NIH Funding Opportunity (RFA-MH-27-125) seeks innovative, phased research to discover and validate mechanistic therapeutic targets for HIV‑associated central nervous system (CNS) complications. Applicants will first identify patient phenotypes with convergent pathophysiology, then use cutting‑edge in‑vitro and in‑vivo models to uncover molecular mechanisms and test interventions. Up to six awards are anticipated, with total estimated funding of $3 million. The solicitation uses the R21/R33 phased innovation activity codes (clinical trials are not allowed) and is open to U.S. public, private, nonprofit, and for‑profit entities (excluding foreign organizations). The deadline for applications is October 28, 2027, with an earliest start date projected for July 2027. • Focus: HIV‑related CNS dysfunction, treatable traits, target discovery. • Activity codes: R21 (exploratory) followed by R33 (development). • Funding: $3 M total (≈ $500 k per award). • Eligible applicants: U.S. higher‑education institutions, state/local governments, nonprofits, for‑profit firms, small businesses, tribal entities. • No clinical trial component allowed; emphasis on pre‑clinical and translational models. • Required deliverables: Data Management & Sharing Plan, annual RPPRs, final close‑out reports.