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- Title
Impact of CYP2B6 983T>C polymorphism on non-nucleoside reverse transcriptase inhibitor plasma concentrations in HIV-infected patients.
- Authors
Christoph Wyen; Heidy Hendra; Martin Vogel; Christian Hoffmann; Heribert Knechten; Norbert H. Brockmeyer; Johannes R. Bogner; Jürgen Rockstroh; Stefan Esser; Hans Jaeger; Thomas Harrer; Stefan Mauss; Jan van Lunzen; Nicole Skoetz; Alexander Jetter; Christiane Groneuer; Gerd Fätkenheuer; Saye H. Khoo; Deirdre Egan; David J. Back
- Abstract
Objectives The aim of this study was to investigate the frequency of CYP2B6 polymorphisms (according to ethnicity) and the influence of heterozygosity and homozygosity on plasma concentrations of efavirenz and nevirapine. Methods Following written informed consent, 225 Caucasians and 146 Blacks were recruited from the German Competence Network for HIV/AIDS. Plasma concentrations of efavirenz and nevirapine were assessed by HPLC, and genotyping for 516G>T, 983T>C and 1459T>C polymorphisms in CYP2B6 was conducted by real-time PCR-based allelic discrimination. Results The minor allele frequency for 516G>T, 983T>C and 1459T>C was 0.29, 0 and 0.08 in Caucasians and 0.34, 0.07 and 0.02 in Blacks, respectively. Two Black patients with the 983C allele receiving efavirenz were identified and both were withdrawn from therapy within 1 week of sampling due to toxicity. In multivariate analyses, efavirenz and nevirapine plasma concentrations were significantly associated with 983T>C (P P = 0.02, respectively), 516G>T (P P = 0.002, respectively) and time of drug analysis post-dose (P P = 0.04) but not nevirapine concentrations, and age was related to nevirapine (P = 0.05) but not efavirenz concentrations. Consistent with other studies, 1459C>T was not associated with plasma concentrations of either drug (P > 0.05 for both drugs). Conclusions This is the first report that the 983T>C genotype (part of the CYP2B6*18 haplotype) impacts on nevirapine plasma concentrations and the first study to assess the impact of 983C homozygosity on efavirenz concentrations. These data have implications for administration of non-nucleoside reverse transcriptase inhibitors to Black patients.
- Subjects
HIV-positive persons; HIV infections; HIV; DNA polymerases
- Publication
Journal of Antimicrobial Chemotherapy (JAC), 2008, Vol 61, Issue 4, p914
- ISSN
0305-7453
- Publication type
Article