Differential Effects of Antiretroviral Drugs on Neurons In Vitro: Roles for Oxidative Stress and Integrated Stress Response.

Mounting evidence suggests that antiretroviral drugs may contribute to the persistence of HIV-associated neurocognitive disorders (HAND), which impact 30%-50% of HIV-infected patients in the post-antiretroviral era. We previously reported that two first generation HIV protease inhibitors, ritonavir and saquinavir, induced oxidative stress, with subsequent neuronal death in vitro, which was reversed by augmentation of the endogenous antioxidant response by monomethyl fumarate. We herein determined whether two newer-generation PIs, darunavir and lopinavir, were deleterious to neurons in vitro.