Sukasem Chonlaphat, Chamnanphon Montri, Koomdee Napatrupron, Santon Siwalee, Jantararoungtong Thawinee, Prommas Santirat, Puangpetch Apichaya, Manosuthi Weerawat
Division of Pharmacogenomics and Personalized Medicine, Department of Pathology, Faculty of Medicine Ramathibodi Hospital, Mahidol University.
Drug Metab Pharmacokinet. 2014;29(4):289-95. doi: 10.2133/dmpk.dmpk-13-rg-077. Epub 2014 Jan 28.
The aim of this study was to assess the influence of host genetic variations and clinical factors in relation to efavirenz level in HIV-1 infected Thai adults. A total of 100 HIV-infected subjects treated with efavirenz/lamivudine/tenofivir were prospectively enrolled. The panel of CYP2A6, CYP2B6 and CYP3A4/5 polymorphisms was genotyped. At steady state, plasma efavirenz concentrations were measured using high performance liquid chromatography. The relationship between host genetic and clinical factors in terms of efavirenz pharmacokinetics in HIV-1 infected Thai adults was analyzed. The minor allele frequency for CYP2A6 -48T>G, CYP2B6 g.18492T>C, CYP3A41B c.-392A>G, CYP3A418 c.878T>C and CYP3A53 c.6986A>G was 0.14, 0.27, 0.01, 0.03 and 0.38, respectively. Univariant and multivariant analysis indicated associations for CYP2B6 g.18492T>C (p < 0.001 and p = 0.001), aspartate aminotransferase (AST; p = 0.001 and p = 0.006) and blood urea nitrogen (BUN; p = 0.011 and p = 0.016) with plasma efavirenz concentration. However, CYP2A6 -48T>G, CYP3A41B c.-392A>G, CYP3A418 c.878T>C and CYP3A53 c.6986A>G had no significant impact on plasma efavirenz concentration in HIV-1 infected Thai adults. The CYP2B6 g.18492T>C polymorphism, AST and BUN were significantly associated with low efavirenz concentrations. The results from this study can be used to improve the prediction of efavirenz plasma concentration and to optimize its dose in antiretroviral therapy.
本研究的目的是评估宿主基因变异和临床因素对感染HIV-1的泰国成年人中依非韦伦水平的影响。前瞻性纳入了100例接受依非韦伦/拉米夫定/替诺福韦治疗的HIV感染受试者。对CYP2A6、CYP2B6和CYP3A4/5多态性进行基因分型。在稳态时，使用高效液相色谱法测量血浆依非韦伦浓度。分析了感染HIV-1的泰国成年人中宿主基因和临床因素在依非韦伦药代动力学方面的关系。CYP2A6 -48T>G、CYP2B6 g.18492T>C、CYP3A41B c.-392A>G、CYP3A418 c.878T>C和CYP3A53 c.6986A>G的次要等位基因频率分别为0.14、0.27、0.01、0.03和0.38。单变量和多变量分析表明，CYP2B6 g.18492T>C（p < 0.001和p = 0.001）、天冬氨酸转氨酶（AST；p = 0.001和p = 0.006）和血尿素氮（BUN；p = 0.011和p = 0.016）与血浆依非韦伦浓度相关。然而，CYP2A6 -48T>G、CYP3A41B c.-392A>G、CYP3A418 c.878T>C和CYP3A53 c.6986A>G对感染HIV-1的泰国成年人血浆依非韦伦浓度没有显著影响。CYP2B6 g.18492T>C多态性、AST和BUN与依非韦伦低浓度显著相关。本研究结果可用于改善依非韦伦血浆浓度的预测，并优化其在抗逆转录病毒治疗中的剂量。
