Publication: CYP2B6 haplotype and biological factors responsible for hepatotoxicity in HIV-infected patients receiving efavirenz-based antiretroviral therapy
Issued Date
2014-01-01
Resource Type
ISSN
18727913
09248579
09248579
Other identifier(s)
2-s2.0-84896491290
Rights
Mahidol University
Rights Holder(s)
SCOPUS
Bibliographic Citation
International Journal of Antimicrobial Agents. Vol.43, No.3 (2014), 292-296
Suggested Citation
Weerawat Manosuthi, Chonlaphat Sukasem, Aroon Lueangniyomkul, Wiroj Mankatitham, Supeda Thongyen, Samruay Nilkamhang, Sukanya Manosuthi, Somnuek Sungkanuparph CYP2B6 haplotype and biological factors responsible for hepatotoxicity in HIV-infected patients receiving efavirenz-based antiretroviral therapy. International Journal of Antimicrobial Agents. Vol.43, No.3 (2014), 292-296. doi:10.1016/j.ijantimicag.2013.10.022 Retrieved from: https://repository.li.mahidol.ac.th/handle/20.500.14594/34640
Research Projects
Organizational Units
Authors
Journal Issue
Thesis
Title
CYP2B6 haplotype and biological factors responsible for hepatotoxicity in HIV-infected patients receiving efavirenz-based antiretroviral therapy
Other Contributor(s)
Abstract
Data on the pharmacogenetic markers of CYP2B6 and biological factors associated with hepatotoxicity in HIV-infected patients receiving an efavirenz-based antiretroviral therapy (ART) regimen are very limited. A total of 134 HIV-infected Thai adults were prospectively enrolled to receive a once-daily regimen of efavirenz 600 mg/tenofovir/lamivudine. Seven single nucleotide polymorphisms (SNPs) within CYP2B6 were genotyped using real-time PCR. At 12 weeks after ART, plasma efavirenz concentrations at 12 h after dosing were measured. The mean ± standard deviation patient age was 37 ± 8 years, and 77.6% were male. The median (IQR) CD4 count was 43 cells/mm3(17-105 cells/mm3). Eighteen patients (13.4%) had positive anti-HCV and 5 patients (3.7%) had positive HBsAg. The frequencies of heterozygous/homozygous mutants of each SNP were 64C>T (11%), 499C>G (0%), 516G>T (55%), 785A>G (63%), 1375A>G (0%), 1459C>T (3%) and 21563C>T (62%). The three most frequent haplotypes identified included*1/*6 (40.3%),*1/*1 (34.3%) and*6/*6 (8.2%). The median (IQR) plasma efavirenz concentration was 2.3 mg/L (1.4-3.7 mg/L). At 24 weeks, median (IQR) serum ALP was 98 mg/dL (73-133 mg/dL) and direct bilirubin was 0.11 mg/dL (0.10-0.19 mg/dL). The proportion of grade 1 and grade 2 elevated serum ALP was 12.7% and 1.5%, respectively. By multivariate analysis, factors associated with high ALP, total bilirubin and direct bilirubin included CYP2B6 haplotype*6/*6, high serum ALP at Week 0 and positive anti-HCV (all P < 0.05). In summary, HIV-infected patients with the pharmacogenetic marker 'CYP2B6 haplotype*6/*6' may have increased susceptibility to hepatotoxicity with efavirenz-based ART. © 2013 Elsevier B.V. and the International Society of Chemotherapy.