Damronglerd Pansachee, Sukasem Chonlaphat, Thipmontree Wilawan, Puangpetch Apichaya, Kiertiburanakul Sasisopin
Deparment of Medicine, Mahidol University, Bangkok, Thailand.
Department of Pathology, Faculty of Medicine Ramathibodi Hospital, Mahidol University, Bangkok, Thailand ; Laboratory for Pharmacogenomics, Somdech Phra Debaratana Medical Center, Faculty of Medicine Ramathibodi Hospital, Mahidol University, Bangkok, Thailand.
Pharmgenomics Pers Med. 2015 Oct 3;8:155-62. doi: 10.2147/PGPM.S86446. eCollection 2015.
We aimed at comparing clinical/immunological outcomes in human immunodeficiency virus (HIV)-infected patients who were treated with CYP2B6-guided and conventional efavirenz (EFV) therapy.
This study was a 24-week prospective randomized controlled trial. Eligible patients were HIV-infected adults yet to start antiretroviral therapy. Twenty-four HIV-infected patients were recruited and randomly assigned to genotype CYP2B6 polymorphism before ART initial dose. Patients with CYP2B6 *6/*6 received 400 mg EFV-based regimen and those with other genotypes received 600 mg EFV-based therapy.
For CYP2B6 polymorphism, 12 patients were extensive metabolizers, ten patients were intermediate metabolizers, and only two patients were poor metabolizers (*6/*6). The overall mean EFV plasma concentrations were similar in both groups. The mean drug concentrations (standard deviation) were 1.675 (0.963), 1.445 (0.778), and 1.899 (0.808) µg/mL at week 4, 12, and 24, respectively. The CYP2B6 *6/*6 patient who received low dose of EFV had lower mean EFV level than those who received a normal dose, 1.916 versus 3.915 µg/mL (P<0.001), respectively. Seventy percent of the patients had neuropsychiatric adverse events, especially dizziness.
There was a trend toward association of the CYP2B6 polymorphism and plasma EFV concentrations in this study. Reduced EFV dose should be considered in CYPB6 *6/*6 carrier to keep the drug concentration in therapeutic range.
我们旨在比较接受CYP2B6基因指导的依非韦伦（EFV）疗法和传统依非韦伦疗法的人类免疫缺陷病毒（HIV）感染患者的临床/免疫结果。
本研究是一项为期24周的前瞻性随机对照试验。符合条件的患者为尚未开始抗逆转录病毒治疗的HIV感染成人。招募了24名HIV感染患者，并在抗逆转录病毒治疗初始剂量前对其进行CYP2B6基因多态性检测。携带CYP2B6 *6/*6的患者接受基于400mg依非韦伦的治疗方案，其他基因型患者接受基于600mg依非韦伦的治疗。
对于CYP2B6基因多态性，12名患者为快代谢型，10名患者为中代谢型，只有2名患者为慢代谢型（*6/*6）。两组的依非韦伦血浆总体平均浓度相似。第4周、12周和24周时的平均药物浓度（标准差）分别为1.675（0.963）、1.445（0.778）和1.899（0.808）μg/mL。接受低剂量依非韦伦的CYP2B6 *6/*6患者的平均依非韦伦水平低于接受正常剂量的患者，分别为1.916和3.915μg/mL（P<0.001）。70%的患者出现神经精神不良事件，尤其是头晕。
本研究中CYP2B6基因多态性与依非韦伦血浆浓度之间存在关联趋势。对于携带CYPB6 *6/*6的患者，应考虑降低依非韦伦剂量，以将药物浓度维持在治疗范围内。
