Central nervous system-penetrating antiretrovirals impair energetic reserve in striatal nerve terminals

摘要: The use of antiretroviral (ARV) drugs with central nervous system (CNS) penetration effectiveness (CPE) may be useful in the treatment HIV-associated neurocognitive disorder (HAND) as well targeting a CNS reservoir strategies to achieve functional cure for HIV. However, increased cognitive deficits are linked at least one these (efavirenz). As mitochondrial dysfunction has been found number ARVs, and such can affect neuronal function, objective this study was assess effects ARV high CPE toxicological profiles on presynaptic nerve terminal energy metabolism. This subcellular region is especially vulnerable that constant supply ATP required proper maintenance neurotransmitter release uptake supporting function. We evaluated acute ten different ARVs from five drug classes rat cortical striatal bioenergetic While bioenergetics were not altered, terminals exposed efavirenz, nevirapine, abacavir, emtricitabine, zidovudine, darunavir, lopinavir, raltegravir, or maraviroc (but indinavir) exhibit reduced spare respiratory capacity (SRC). Further examination efavirenz revealed concentration-dependent impairment maximal respiration SRC reduction intraterminal levels. Depletion synapse underlie its contribute treated HIV infection.