title: Absence of a relation between efavirenz plasma concentrations and toxicity-driven efavirenz discontinuations in the EuroSIDA study.
abstract: BACKGROUND
  Co1nflicting data exist regarding the effect of efavirenz (EFV) plasma concentrations on central nervous system (CNS) toxicity. We aimed to determine whether patients with high EFV plasma concentrations have an increased likelihood of toxicity-driven EFV discontinuations.
  
  
  METHODS
  EFV plasma concentrations were measured from patients in the EuroSIDA study starting EFV after 1 January 1999. Patients with a plasma concentration available were divided into those that discontinued EFV because of any toxicity or by the choice of the patient or physician within 2 years (TOXPC group) and those that continued EFV for > or = 2 years (no toxicity group). Multivariable logistic regression modelling was used to investigate the effects of the EFV plasma concentration and those of other potentially relevant factors on the risk of toxicity-induced EFV discontinuations.
  
  
  RESULTS
  A total of 843 patients were included. Of these patients, 138 patients (16.4%) discontinued EFV because of TOXPC and 705 (83.6%) patients continued EFV for 22 years. A total of 20 (14.5%) patients in the TOXPC group had high EFV plasma concentrations (>4.0 mg/l) compared with 99 (14.0%) patients in the no toxicity group (P = 0.890). A positive hepatitis C status (P = 0.026), but not the EFV plasma concentration, was an independent predictor of toxicity-driven EFV discontinuations.
  
  
  CONCLUSIONS
  No association was found between EFV plasma concentrations and the risk of EFV discontinuations because of (CNS) toxicity. This result questions the designation of EFV plasma concentrations >4.0 mg/l as being 'toxic', at least when defined by treatment discontinuation.
authors.affiliation: Department of Clinical Pharmacy, Radboud University Nijmegen Medical Center, Nijmegen, The Netherlands. m.vanluin@akf.umcn.nl
authors.forename: Matthijs
authors.initials: M
authors.lastname: van Luin
authors.forename: Wendy P
authors.initials: WP
authors.lastname: Bannister
authors.forename: Amanda
authors.initials: A
authors.lastname: Mocroft
authors.forename: Peter
authors.initials: P
authors.lastname: Reiss
authors.forename: Giovanni
authors.initials: G
authors.lastname: Di Perri
authors.forename: Gilles
authors.initials: G
authors.lastname: Peytavin
authors.forename: José
authors.initials: J
authors.lastname: Molto
authors.forename: Anders
authors.initials: A
authors.lastname: Karlson
authors.forename: Antonella
authors.initials: A
authors.lastname: Castagna
authors.forename: Marek
authors.initials: M
authors.lastname: Beniowski
authors.forename: Jens D
authors.initials: JD
authors.lastname: Lundgren
authors.forename: David M
authors.initials: DM
authors.lastname: Burger