Mechanistic Evaluation of Therapeutic Targets derived from Treatable Traits to Improve CNS Outcomes in People with HIV (R21/R33 Clinical Trial Not Allowed)
NIH supports phased research to identify and validate modifiable mechanisms and therapeutic targets for central nervous system complications in people with HIV; clinical trials are not allowed.
Funder: National Institutes of Health
Due Dates: November 9, 2026 (Applications) | October 28, 2027 (Applications)
Funding Amounts: R21: up to $275,000 direct costs over 2 years; R33: up to $650,000 direct costs annually for 3 years
Summary: Supports patient-informed mechanistic research to identify and validate modifiable therapeutic targets for HIV-associated central nervous system complications.
Key Information: Applications must propose both R21 and R33 phases with transition milestones; clinical trials and foreign components are prohibited.
Description
This NIH Phased Innovation Award, supported by NIMH, NIDA, and NINDS, funds therapeutic target discovery for central nervous system (CNS) complications in people with HIV. It focuses on patient-informed phenotypes: clinically and biologically characterized subgroups sharing disease mechanisms. Within these subgroups, “treatable traits” are measurable biological features linked to disease processes and amenable to therapeutic modulation.
The program supports a bedside-to-bench approach, moving from phenotype identification and mechanistic hypotheses to experimental validation. Encouraged platforms include patient-derived organoids, primary CNS cell cultures, microphysiological systems, and relevant in vivo models. Research may address neuroimmune dysregulation, synaptic dysfunction, neurotransmitter imbalance, and neuronal injury. The R21 phase develops platforms and screens mechanisms or targets; the R33 phase validates mechanisms, tests target engagement, and links target modulation to functional improvement and translational readiness.
