ORIGINAL ARTICLESInfluence of CYP2B6 polymorphism on plasma and intracellular concentrations and toxicity of efavirenz and nevirapine in HIV-infected patientsRotger, Margalidaa *; Colombo, Sarab *; Furrer, Hansjakobc *; Bleiber, Gabrielaa; Buclin, Thierryb; Lee, Belle L.c; Keiser, Oliviad; Biollaz, Jérômeb; Décosterd, Laurentb; Telenti, Amalioathe Swiss HIV Cohort StudyAuthor Information aInstitute of Microbiology and Section of Infectious Diseases, University Hospital, Lausanne bDivision of Clinical Pharmacology, University Hospital, Lausanne cDivision of Infectious Diseases, University Hospital, Bern dData Center Swiss HIV Cohort Study, Lausanne, Switzerland Sponsorship: Support for this work was provided by the Swiss National Science Foundation (grant 3345C0-100935/1), by the Swiss HIV Cohort Study (Swiss National Science Foundation, grant 3345-062041), and by the Santos Suarez Foundation. MR is supported by an award from the Fondo de Investigacion Sanitaria, Spain (grant BF03/0005). Correspondence and requests for reprints to Dr Amalio Telenti, Institute of Microbiology, Bugnon 48, CHUV, 1011 Lausanne E-mail: [email protected] Received 19 July 2004 Accepted 12 October 2004 *Contributed equally to the work. §The members of the Swiss HIV Cohort Study are M. Battegay (Chairman of the Scientific Board), M.-C. Bernard, E. Bernasconi, H. Bucher, Ph. Bürgisser, M. Egger, P. Erb, W. Fierz, M. Flepp (Chairman of the Clinical and Laboratory Committee), P. Francioli (President of the SHCS, Centre Hospitalier Universitaire Vaudois, CH-1011-Lausanne), H.J. Furrer, M. Gorgievski, H. Günthard, P. Grob, B. Hirschel, C. Kind, Th. Klimkait, B. Ledergerber, U. Lauper, M. Opravil, F. Paccaud, G. Pantaleo, L. Perrin, J.-C. Piffaretti, M. Rickenbach (Head of Data Center), C. Rudin (Chairman of the Mother & Child Substudy), J. Schupbach, A. Telenti, P. Vernazza, Th. Wagels, R. Weber. Pharmacogenetics and Genomics: January 2005 - Volume 15 - Issue 1 - p 1-5 Buy Abstract Background Efavirenz (EFV) and nevirapine (NVP) are metabolized by cytochrome P450 2B6 (CYP2B6). Allele 516 G>T (Gln172His) is associated with diminished activity of this isoenzyme, and may lead to differences in drug exposure. Methods We evaluated this allele as a pharmacogenetic marker of EFV and NVP pharmacokinetics and EFV toxicity in 167 participants receiving EFV and 59 receiving NVP recruited within the genetics project of the Swiss HIV Cohort Study. Drug concentrations were measured in plasma and in peripheral blood mononuclear cells (PBMCs) from the same sample. Neuropsychological toxicity of EFV (sleep disorders, mood disorders, fatigue) was assessed using a standardized questionnaire. Results and conclusions CYP2B6 516TT was associated with greater plasma and intracellular exposure to EFV, and greater plasma exposure to NVP. Intracellular drug concentration, and CYP2B6 genotype were predictors of EFV neuropsychological toxicity. CYP2B6 genotyping may be useful to complement an individualization strategy based on plasma drug determinations to increase the safety and tolerability of EFV. © 2005 Lippincott Williams & Wilkins, Inc.