Efavirenz and the CNS: what we already know and questions that need to be answered

J Antimicrob Chemother. 2015 Oct;70(10):2693-708. doi: 10.1093/jac/dkv183. Epub 2015 Jul 22.

Abstract

The NNRTI efavirenz has long been one of the most frequently employed antiretroviral drugs in the multidrug regimens used to treat HIV infection, in accordance with its well-demonstrated antiretroviral efficacy and favourable pharmacokinetics. However, growing concern about its adverse effects has sometimes led to efavirenz being replaced by other drugs in the initial treatment selection or to switching of therapy to efavirenz-free regimens in experienced patients. Neurological and neuropsychiatric reactions are the manifestations most frequently experienced by efavirenz-treated patients and range from transitory effects, such as nightmares, dizziness, insomnia, nervousness and lack of concentration, to more severe symptoms including depression, suicidal ideation or even psychosis. In addition, efavirenz has recently been associated with mild/moderate neurocognitive impairment, which is of specific relevance given that half of the patients receiving ART eventually suffer some form of HIV-associated neurocognitive disorder. The mechanisms responsible for efavirenz-induced neurotoxicity are unclear, although growing evidence points to disturbances in brain mitochondrial function and bioenergetics. This review offers a comprehensive overview of the current evidence on the interaction that efavirenz displays with the CNS, including the penetration and concentration of the drug in the brain. We discuss the prevalence, types and specificities of its side effects and recently uncovered cellular mechanisms that may be involved in their development.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Anti-HIV Agents / adverse effects*
  • Anti-HIV Agents / pharmacology
  • Anti-HIV Agents / therapeutic use
  • Antiretroviral Therapy, Highly Active / adverse effects
  • Benzoxazines / adverse effects*
  • Benzoxazines / pharmacology
  • Benzoxazines / therapeutic use
  • Central Nervous System / drug effects*
  • Central Nervous System Diseases / etiology
  • Cytochrome P-450 CYP2B6 / genetics
  • Cytochrome P-450 Enzyme Inhibitors / adverse effects*
  • Cytochrome P-450 Enzyme Inhibitors / pharmacology
  • Cytochrome P-450 Enzyme Inhibitors / therapeutic use
  • Disease Models, Animal
  • HIV Infections / complications
  • HIV Infections / drug therapy
  • HIV Infections / genetics
  • Humans
  • Pharmacogenetics
  • Polymorphism, Single Nucleotide
  • Reverse Transcriptase Inhibitors / adverse effects*
  • Reverse Transcriptase Inhibitors / pharmacology
  • Reverse Transcriptase Inhibitors / therapeutic use

Substances

  • Anti-HIV Agents
  • Benzoxazines
  • Cytochrome P-450 Enzyme Inhibitors
  • Reverse Transcriptase Inhibitors
  • Cytochrome P-450 CYP2B6
  • efavirenz