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- Title
Impact of CYP2B6 983T>C polymorphism on non-nucleoside reverse transcriptase inhibitor plasma concentrations in HIV-infected patients.
- Authors
Wyen, Christoph; Hendra, Heidy; Vogel, Martin; Hoffmann, Christian; Knechten, Heribert; Brockmeyer, Norbert H; Bogner, Johannes R; Rockstroh, Jürgen; Esser, Stefan; Jaeger, Hans; Harrer, Thomas; Mauss, Stefan; van Lunzen, Jan; Skoetz, Nicole; Jetter, Alexander; Groneuer, Christiane; Fätkenheuer, Gerd; Khoo, Saye H; Egan, Deirdre; Back, David J
- Abstract
<bold>Objectives: </bold>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.<bold>Methods: </bold>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.<bold>Results: </bold>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 Two Black patients with the 983C allele receiving efavirenz were identified and both were withdrawn from therapy within 1 week of sampling due to toxicity.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 < 0.0001 and P = 0.02, respectively), 516G>T (P < 0.0001 and P = 0.002, respectively) and time of drug analysis post-dose (P < 0.0001 for both). Body mass index was independently related to efavirenz (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).<bold>Conclusions: </bold>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.
- Publication
Journal of Antimicrobial Chemotherapy (JAC), 2008, Vol 61, Issue 4, p914
- ISSN
0305-7453
- Publication type
journal article
- DOI
10.1093/jac/dkn029