Impact of CYP2B6 983T>C polymorphism on non-nucleoside reverse transcriptase inhibitor plasma concentrations in HIV-infected patients.
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Impact of CYP2B6 983T>C polymorphism on non-nucleoside reverse transcriptase inhibitor plasma concentrations in HIV-infected patients. / 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; Owen, Andrew.
In: J ANTIMICROB CHEMOTH, Vol. 61, No. 4, 4, 2008, p. 914-918.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
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TY - JOUR
T1 - Impact of CYP2B6 983T>C polymorphism on non-nucleoside reverse transcriptase inhibitor plasma concentrations in HIV-infected patients.
AU - Wyen, Christoph
AU - Hendra, Heidy
AU - Vogel, Martin
AU - Hoffmann, Christian
AU - Knechten, Heribert
AU - Brockmeyer, Norbert H
AU - Bogner, Johannes R
AU - Rockstroh, Jürgen
AU - Esser, Stefan
AU - Jaeger, Hans
AU - Harrer, Thomas
AU - Mauss, Stefan
AU - van Lunzen, Jan
AU - Skoetz, Nicole
AU - Jetter, Alexander
AU - Groneuer, Christiane
AU - Fätkenheuer, Gerd
AU - Khoo, Saye H
AU - Egan, Deirdre
AU - Back, David J
AU - Owen, Andrew
PY - 2008
Y1 - 2008
N2 - 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 Two Black patients with the 983C allele receiving efavirenz were identified and both were withdrawn from therapy within 1 week of sampling due to toxicity.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 <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). 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.
AB - 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 <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). 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.
M3 - SCORING: Zeitschriftenaufsatz
VL - 61
SP - 914
EP - 918
JO - J ANTIMICROB CHEMOTH
JF - J ANTIMICROB CHEMOTH
SN - 0305-7453
IS - 4
M1 - 4
ER -
