title: High plasma efavirenz concentration and CYP2B6 polymorphisms in Thai HIV-1 infections.
abstract: Efavirenz is mainly metabolized by cytochrome P450 2B6 (CYP2B6). This study aimed to examine the frequencies of CYP2B6 and the association between CYP2B6 polymorphisms and plasma efavirenz concentrations in an HIV-1 infected Thai population. Mid-dose plasma efavirenz concentration was determined at 12 weeks following the initiation of an antiretroviral therapy (tenofovir, lamivudine and efavirenz) in 100 Thai adults with HIV-1 infection using high-performance liquid chromatography. Candidate CYP2B6 polymorphisms (c.64C>T, c.499C>G, c.516G>T, c.785A>G, c.1375A>G, c.1459C>T) were conducted by real-time PCR-based allelic discrimination. The most frequent polymorphisms among this cohort were the CYP2B6 c.785A>G and c.516G>T, which had a frequency of 0.36 and 0.32, respectively. From the cases observed, two single nucleotide polymorphisms (SNPs) (c.516G>T and c.785A>G) were significantly associated with high efavirenz plasma levels (p < 0.05). The most frequent haplotypic combinations were *1/*6, *1/*1, *1/*2 and *6/*6 at a frequency of 42.0%, 32.0%, 8.0% and 7.0%, respectively. Increased plasma concentrations of efavirenz were present in individuals with CYP2B6 *6/*6 [7.210 mg/L; interquartile range (IQR), 5.020-9.260] when compared to those with CYP2B6*1/*1 (1.570 mg/L; IQR, 1.295-2.670), p < 0.001. In our study, the impact of SNPs which are correlated with a high level of efavirenz plasma concentrations was found. The genetic configuration of SNPs which are associated with high plasma efavirenz levels may be useful in optimizing the efavirenz dose that is used in HIV-1 infected patients.
authors: Division of Pharmacogenomics and Personalized Medicine, Department of Pathology, Faculty of Medicine, Ramathibodi Hospital, Mahidol University.
authors: Chonlaphat
authors: C
authors: Sukasem
authors: Montri
authors: M
authors: Chamnanphon
authors: Napatrupron
authors: N
authors: Koomdee
authors: Apichaya
authors: A
authors: Puangpetch
authors: Siwalee
authors: S
authors: Santon
authors: Thawinee
authors: T
authors: Jantararoungtong
authors: Santirat
authors: S
authors: Prommas
authors: Wasun
authors: W
authors: Chantratita
authors: Weerawat
authors: W
authors: Manosuthi
mesh_terms: D000328:Adult; D000480:Alkynes; D001189:Aryl Hydrocarbon Hydroxylases / Q000235:genetics*; D044466:Asian People / Q000235:genetics*; D048588:Benzoxazines / Q000097:blood* / Q000627:therapeutic use*; D003521:Cyclopropanes; D065702:Cytochrome P-450 CYP2B6; D015658:HIV Infections / Q000188:drug therapy* / Q000235:genetics; D006801:Humans; D020641:Polymorphism, Single Nucleotide; D013785:Thailand
chemical_list: D000480:Alkynes; D048588:Benzoxazines; D003521:Cyclopropanes; D001189:Aryl Hydrocarbon Hydroxylases; C585599:CYP2B6 protein, human; D065702:Cytochrome P-450 CYP2B6; C098320:efavirenz