中国获得性免疫缺陷综合征患者依非韦伦减量应用的疗效及安全性

Efficacy and safety of efavirenz dose reduction in Chinese AIDS patients

目的考察中国获得性免疫缺陷综合征患者依非韦伦减量应用的疗效和安全性。方法通过检测患者依非韦伦血药浓度、CYP2B6 516 G> T基因型,筛选出血药浓度> 6. 0 mg·L^(-1)、基因型为516 GT或516 TT且同意进行减量的患者纳入本研究。患者入组后先将依非韦伦剂量减至400 mg,qd,若2周后血药浓度仍> 4. 0 mg·L^(-1)且患者本人仍同意减量,则将剂量减为200 mg,并测定2周后的血药浓度。记录患者减量前及48周时的实验室检查、CD4^+计数(每12周常规检测一次)、HIV病毒载量数据,并通过问卷调查收集患者中枢神经系统相关不良反应的数据。结果共入组31例获得性免疫缺陷综合征患者,516 GT和TT基因型的比例分别为12. 9%(4例)和87. 1%(27例)。减量前31例患者的血药浓度为(9. 60±2. 80)mg·L^(-1),剂量减为400 mg 2周后血药浓度为(5. 78±2. 08) mg·L^(-1),18例减为200 mg的患者减量后2周血药浓度为(4. 04±1. 02) mg·L^(-1)。减量前31例患者的CD4^+计数均值为(243. 2±123. 6) cells·μL^(-1),48周时为(323. 4±120. 8) cells·μL^(-1),P <0. 01。减量前HIV病毒载量均值为(42. 5±5. 7) copies·m L^(-1),48周时为(43. 7±6. 8) copies·m L^(-1),P> 0. 05。减量前和48周时患者的血生化和血常规各项指标检查结果均无显著改变,P值均> 0. 05。减量前部分患者存在乏力、眩晕、头疼、异梦、注意力不集中、失眠、焦虑以及健忘等不良反应症状,这些症状在48周时有明显改善,部分患者的不良反应症状消失。结论参照CYP2B6 516 G> T基因型,将中国获得性免疫缺陷综合征患者依非韦伦剂量由600 mg减至400 mg或200mg,48周后仍能获得理想的抗病毒疗效,且能改善患者存在的中枢神经系统不良反应症状。

AIM To evaluate the efficacy and safety of efavirenz （EFV） dosage reduction in Chinese ac- quired immunodeficiency syndrome（AIDS） patients. METHODS Among the patients with EFV plasma concentrations 〉6.0mg·L^-1 as well as with CYP2B6 516 GT or 516 TT genotype, those who agreed to accept an EFV dosage reduction, were enrolled in this study. At first, 600 mg EFV dosage was reduced to 400 mg and the EFV concentration was determined after 2 weeks. Afterwards, the EFV dosage was further reduced to 200 mg if the EFV concentration was 〉 4.0mg·L^-1 and the patients agreed to accept a further dosage reduction. Similarly, the EFV plasma concentration was measured 2 weeks after the start of a 200 mg dosage. Data of laboratory tests, including HIV viral load, were recorded before dosage reduction and by the end of 48-week follow-up period. CD4^＋ count was examined every 12 weeks during the follow-up period. Data of adverse reactions of central nervous system were collected by means of questionnaire surveys before dosage reduction and by the end of 48 weeks follow-up. RESULTS Among the 31 patients enrolled in this study, those with 516 GT and TY genotypes accounted for 12.9% （4 cases） and 87.1% （27 cases） , respectively. The mean value of EFV plasma concentrations was （9.60±2.80）mg·L^-1 before dosage reduction, and it became （5.78 ±2.08）mg·L^-1 when the dosage was reduced to 400 mg after 2 weeks. The mean concentration of 18 patients with EFV 200 mg was （4.04 ~ 1.02）mg·L^-1 at 2 weeks after reduction. The mean value of CD4^＋ count of the patients at 48 weeks （323.4±120.8 ） cells·μL^-1）was significantly high compared with that before dosage reduction （243.2±123.6） cells·μL^-1 , P 〈0.01. There were no statistically significant difference in HIV viral load [ （ 42.5±5.7 ） vs （43.7±6.8 ） copies ·μL^-1,P 〉 0.05 ] or other laboratory tests end of 48-week follow-up period （ results between data collected before dosage reduction and those collected at the P 〉 0.05 ）. Adverse reactions which happened in some patients including weak-hess, dizziness, headache, strange dreams, inattention, insomnia, anxiety and amnesia were partly improved or disappeared at 48 weeks. CONCLUSION The antiviral efficacy of EFV-containing ART is not affected within the 48 weeks after reducing the EFV dosage from 600 mg to 400 mg or 200 mg for Chinese AIDS patients. Moreover, the symptoms of adverse reactions of central nervous system are also improved after dosage reduction.