Absence of a relation between efavirenz plasma concentrations and toxicity-driven evafirenz discontinuations in the EuroSIDA study

Motthijs van Luin, Wendy P. Bannister, Amanda Mocroft, Peter Reiss, Giovanni Di Perri, Gilles Peytavin, José Molto, Anders Karlson, Antonella Castagna, Marek Beniowski, Jens D. Lundgren

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Abstract

Background: Conflicting 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 ≥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 ≥2 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.

Original languageEnglish
Pages (from-to)75-83
Number of pages9
JournalAntiviral Therapy
Volume14
Issue number1
Publication statusPublished - 2009

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ASJC Scopus subject areas

  • Pharmacology
  • Pharmacology (medical)
  • Infectious Diseases

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van Luin, M., Bannister, W. P., Mocroft, A., Reiss, P., Di Perri, G., Peytavin, G., ... Lundgren, J. D. (2009). Absence of a relation between efavirenz plasma concentrations and toxicity-driven evafirenz discontinuations in the EuroSIDA study. Antiviral Therapy, 14(1), 75-83.

Absence of a relation between efavirenz plasma concentrations and toxicity-driven evafirenz discontinuations in the EuroSIDA study. / van Luin, Motthijs; Bannister, Wendy P.; Mocroft, Amanda; Reiss, Peter; Di Perri, Giovanni; Peytavin, Gilles; Molto, José; Karlson, Anders; Castagna, Antonella; Beniowski, Marek; Lundgren, Jens D.

In: Antiviral Therapy, Vol. 14, No. 1, 2009, p. 75-83.

Research output: Contribution to journalArticle

van Luin, M, Bannister, WP, Mocroft, A, Reiss, P, Di Perri, G, Peytavin, G, Molto, J, Karlson, A, Castagna, A, Beniowski, M & Lundgren, JD 2009, 'Absence of a relation between efavirenz plasma concentrations and toxicity-driven evafirenz discontinuations in the EuroSIDA study', Antiviral Therapy, vol. 14, no. 1, pp. 75-83.
van Luin, Motthijs ; Bannister, Wendy P. ; Mocroft, Amanda ; Reiss, Peter ; Di Perri, Giovanni ; Peytavin, Gilles ; Molto, José ; Karlson, Anders ; Castagna, Antonella ; Beniowski, Marek ; Lundgren, Jens D. / Absence of a relation between efavirenz plasma concentrations and toxicity-driven evafirenz discontinuations in the EuroSIDA study. In: Antiviral Therapy. 2009 ; Vol. 14, No. 1. pp. 75-83.
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abstract = "Background: Conflicting 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 ≥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 ≥2 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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AU - van Luin, Motthijs

AU - Bannister, Wendy P.

AU - Mocroft, Amanda

AU - Reiss, Peter

AU - Di Perri, Giovanni

AU - Peytavin, Gilles

AU - Molto, José

AU - Karlson, Anders

AU - Castagna, Antonella

AU - Beniowski, Marek

AU - Lundgren, Jens D.

PY - 2009

Y1 - 2009

N2 - Background: Conflicting 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 ≥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 ≥2 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.

AB - Background: Conflicting 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 ≥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 ≥2 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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