拉米夫定-齐多夫定、依非韦伦联合方案对HIV-1感染人群初始治疗的疗效评价和现场管理模式探讨

Evaluation of the efficacy of lamivudine-zidovudine-efavirenz triple combination regimen as initial therapy for the HIV-1 infected people in a rural area of China and field management

目的采用拉米夫定-齐多夫定(3CT-AZT)、依非韦仑(EFV)联合治疗方案对中国农村HIV-1感染者治疗52周,评价其疗效和安全性,并探讨如何在资源匮乏地区建立国际标准的研究现场以及抗反转录病毒药物(ARV)不良反应的管理方法和策略。方法自2005年5月至2006年2月共入选100例18岁以上、CD4+T淋巴细胞(CD4)<350/μL、未经抗病毒治疗的HIV-1慢性感染者,接受每日2次3CT-AZT和1次睡前服用EFV600mg持续52周的前瞻性、开放性的临床试验,分别于治疗1、2、3、4、8、12、24、36、48和52周末随访检查,详细记录病毒载量(VL)、T淋巴细胞亚群和耐药情况以及其他生化指标,记录和分析抗病毒药物不良反应。结果①在中国贫困地区建立国际标准的治疗研究现场,并建立了药物不良反应分级报告、转诊和会诊网络。②治疗前CD4计数和VL分别为(204.0±101.0)个/μL和(4.47±0.87)log拷贝/mL。治疗结束时,CD4计数升至(313±137.2)个/μL,87例患者VL<400拷贝/mL。③三级及以上不良事件者13例。④至2007年2月4日,72例到达研究终点,28例提前退出研究。结论①3CT-AZT与EFV联合治疗可以有效抑制HIV-1复制,明显改善机体免疫功能,多数不良事件轻微。②在农村地区开展艾滋病临床治疗研究可采用地方CDC和医院共同参与的模式。

Objective China CIPRA is an integrated AIDS research project funded by the US NIH to evaluate the efficacy, safety and tolerability of Combivir （lamivudine ＋ zidovudine） and efavirenz administered for 52 weeks to HIV- 1-infected patients in a rural area of China. Methods From May 2005 to Feb 2006, 100 HIV-1 infected, ART-naive patients with CD4 〈350 cells/μL were enrolled. Patients received lamivudine 150 mg/zidovudine 300 mg twice daily ＋ efavirenz 600 mg daily for 52 performed on weeks 0, 1, 2, weeks. Follow-up visits were 3, 4, 8, 12, 24, 36, 48 and 52. Adverse effects were coded using MeDRA. Results Mean baseline CD4 and viral load （VL） were （204.0 ±101.0）/μL and （4.47 ±0.87） log10 copies/mL, respectively, compared to （313± 137.2）/μL and 87% had VL〈400 copies/mL at week 52. Thirteen eases of Grade 3 or 4 adverse events were reported, including anemia （7） ; abnormal liver function （2） ; skin rash （1） ; visual disturbance （1） ; diabetic ketoacidosis （l） ; heart failure （ 1 ） ; and cognitive behavioral/attention disorder （ 1 ）. By February 24, 2007, seventy-two participants completed the one-year study while the other 28 subjects withdrew early. Conclusions Results from our study indicated that treatment of HIV with Combivir and Stocrin can effectively inhibit the replication of HIV- 1, significantly improve the immunity of patients. Most of the adverse events were mild and resolved with ongoing treatment. Country hospitals in rural area of China can conduct international HIV/AIDS research jointly with local center for disease control （CDC）.