Efavirenz: What is known about the cellular mechanisms responsible for its adverse effects.

The HIV infection remains an important health problem worldwide. However, due to the efficacy of combined antiretroviral therapy (cART), it has ceased to be a mortal condition, becoming a chronic disease instead. Efavirenz, the most prescribed non-nucleoside analogue reverse transcriptase inhibitor (NNRTI), has been a key component of cART since its commercialization in 1998. Though still a drug of choice in many countries, its primacy has been challenged by the arrival of newer antiretroviral agents with better toxicity profiles and treatment adherence. The major side effects related to EFV have been widely described in clinical studies, however the mechanisms that participate in their pathogenesis remain largely ununderstood. This review provides an insight into the cellular and molecular mechanisms responsible for the development of the most significant undesired effects induced by efavirenz, both short- and long-term, revealed by in vitro and in vivo experimental pharmacological research. Growing evidence implicates the drug in energy metabolism, mitochondrial function, and other cellular processes involved in stress responses including oxidative stress, inflammation and autophagy.