In vitro and Ex vivo Neurotoxic Effects of Efavirenz are Greater than Those of Other Common Antiretrovirals.

In vitro and Ex vivo Neurotoxic Effects of Efavirenz are Greater than Those of Other Common Antiretrovirals. Neurochem Res. 2017 Aug 02;: Authors: Ciavatta VT, Bichler EK, Speigel IA, Elder CC, Teng SL, Tyor WR, García PS Abstract Although antiretroviral (ARV) therapy has reduced the incidence of severe dementia associated with HIV infection, there has been a rise in milder neurocognitive complaints. Data from HIV patients taking ARVs have shown measurable neurocognitive improvements during drug cessation, suggesting a neurotoxic role of the therapy itself. Mechanisms underlying potential ARV neurotoxicity have not been thoroughly investigated, however pathologic oxidative stress and mitochondrial dysfunction have been suspected. Using DIV 16 primary rat cortical neuron culture, we tested eight ARVs from the three most commonly prescribed ARV classes: nucleoside/nucleotide reverse transcriptase inhibitors (NRTIs/NtRTIs), non-nucleoside reverse transcriptase inhibitors (NNRTIs), and protease inhibitors (PIs) for effects on neuron viability and morphology after 24 h of drug exposure. Of the tested NRTIs, only stavudine at nearly 100 times the target plasma concentration affected neuron viability with no appreciable change in morphology. Dideoxyinosine induced dendritic simplification at 100 times target plasma concentrations, but did not adversely affect viability. The sole NtRTI, tenofovir, induced dendritic simplification at approx...
Source: Neurochemical Research - Category: Neuroscience Authors: Tags: Neurochem Res Source Type: research