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.
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