Project Grant R21MH132159

This $396,541 Project Grant award from the National Institute of Mental Health (NIMH) under the Mental Health Research Grants program (CFDA 93.242) aims to uncover fundamental mechanisms and key features governing the interactions between antiretroviral drugs (ARVs) and the blood-brain barrier (BBB) components. The overall goal is to improve the ability of ARVs to penetrate and treat HIV infection in the brain.

The University of Colorado, as the prime awardee, will employ a physiologically relevant in vitro BBB model combined with atomistic simulations to identify properties of two classes of ARVs - protease inhibitors and nucleoside reverse transcriptase inhibitors - that mediate their transport across the BBB. The research will determine the molecular mechanisms of ARV binding to the BBB lipid membrane and efflux proteins, quantify ARV transport across the BBB, and develop machine learning models to predict ARV/BBB interactions that govern transport. This collaborative, iterative approach aims to generate data to create accurate computational models and directly validate model predictions using the novel in vitro BBB system. The findings are expected to facilitate the design of new ARVs that can better penetrate and treat HIV infection in the brain.