title: [Evidence-based therapeutic drug monitoring for efavirenz].
abstract: The efavirenz, a non nucleoside reverse transcriptase inhibitor of HIV-1, presents a marked pharmacokinetics variability related to an intense hepatic metabolism. Efavirenz is also a potent inducer. Central nervous system (CNS) toxicity associated with efavirenz therapy is a major cause of non adherence and therefore treatment failure. The literature has been analyzed to evaluate the level of evidence of the interest of a therapeutic drug monitoring for efavirenz. Several studies have reported that an efavirenz plasma concentration >1 000 ng/mL is a predictive factor of the viral response. Efavirenz plasma concentrations >4 000 ng/mL were associated to an increase frequency of CNS side effects. CNS toxicity was also more frequent in patients carrying the 516G > T mutation (CYP2B6*6 allele), associated with a significantly greater efavirenz plasma exposure. Non-randomized studies have reported the interest of efavirenz therapeutic drug monitoring to optimize viral response and prevent CNS toxicity, allowing to suggest a level of evidence "recommended" for efavirenz.
authors.affiliation: Laboratoire de Pharmacocinétique et Toxicologie, Hôpital de La Timone, Marseille, France. caroline.solas@ap-hm.fr
authors.forename: Caroline
authors.initials: C
authors.lastname: Solas
authors.forename: Marie-Claude
authors.initials: MC
authors.lastname: Gagnieu
mesh_terms: D000480:Alkynes; D019380:Anti-HIV Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000191:economics / Q000493:pharmacokinetics / Q000627:therapeutic use*; D048588:Benzoxazines / Q000008:administration & dosage / Q000009:adverse effects / Q000191:economics / Q000493:pharmacokinetics / Q000627:therapeutic use*; D002986:Clinical Trials as Topic; D003521:Cyclopropanes; D004305:Dose-Response Relationship, Drug; D016903:Drug Monitoring; D019317:Evidence-Based Medicine; D015658:HIV Infections / Q000188:drug therapy*; D006801:Humans; D009422:Nervous System Diseases / Q000139:chemically induced; D018894:Reverse Transcriptase Inhibitors / Q000009:adverse effects / Q000191:economics / Q000493:pharmacokinetics / Q000627:therapeutic use*
chemical_list: D000480:Alkynes; D019380:Anti-HIV Agents; D048588:Benzoxazines; D003521:Cyclopropanes; D018894:Reverse Transcriptase Inhibitors; C098320:efavirenz