摘要
目的系统评价早期抗逆转录病毒治疗（antiretroviral therapy,ART）对无症状HIV感染者的有效性和安全性,探讨无症状HIV感染者ART的最佳启动时机。方法计算机检索Pub Med、EMbase、The Cochrane Library（2016年4期）、CBM、CNKI、VIP及Wan Fang Data数据库,全面搜集有关无症状HIV感染者ART最佳启动时机或早期治疗的随机对照试验（RCT）。检索时限均从1996年1月至2016年4月。由2位研究员按纳入与排除标准独立筛选文献、提取资料并评价偏倚风险后,采用Rev Man 5.3软件进行Meta分析。结果共纳入4个RCT,8 751例患者。Meta分析结果显示,在CD4^＋T淋巴细胞计数（CD4计数）≥350个/μL时,包括CD4计数≥500个/μL时启动ART,相对于延迟至CD4计数〈350个/μL时启动ART治疗,更能给HIV感染者带来明显获益：①在CD4计数≥350个/μL时启动ART,患者AIDS病情进展的风险显著下降[RR=0.49,95%CI（0.38,0.64）,P〈0.001];若在CD4计数≥500个/μL时就启动治疗,AIDS病情进展风险还可进一步下降[RR=0.38,95%CI（0.24,0.59）,P〈0.001];②在CD4^＋计数≥350个/μL时启动ART,患者发生严重非AIDS相关事件的风险显著下降[RR=0.58,95%CI（0.40,0.83）,P=0.003];③在CD4计数≥350或500个/μL时启动ART,相较于延迟启动治疗的患者,两组全因死亡率[RR=0.70,95%CI（0.48,1.02）,P=0.06]以及随访期间发生严重不良反应事件的风险[RR=0.67,95%CI（0.38,1.20）,P=0.18]的差异并无统计学意义。结论本研究结果支持对所有CD4^＋计数在350～500个/μL的无症状HIV感染者启动ART。针对CD4计数在500个/μL以上的患者,亦建议启动治疗。随着治疗覆盖面的扩大和治疗时间的延长,应进一步加强患者的服药依从性教育和随访管理,控制耐药毒株在人群中的流行,预防长期治疗带来的远期不良反应。
Objective To systematically evaluate the efficacy and safety of early initiation of antiretroviral therapy（ART） in asymptomatic HIV-infected, treatment-naive adults and adolescents. To assess the evidence for the optimal time to initiate ART. Methods Databases including Pub Med, EMbase, The Cochrane Library（Issue 4, 2016）, CBM, CNKI, VIP and Wan Fang Data were searched to collect randomized controlled trials（RCTs） about early initiation and optimal time to initiate ART in asymptomatic, treatment-naive HIV-infected patients from January 1996 to April 2016. Two review authors independently assessed study eligibility, extracted data and graded methodological quality. Data extraction and methodological quality were checked by a third author who resolved differences when these arose. We meta-analysed dichotomous outcomes using the risk ratio（RR） and report the 95 % confidence intervals（ 95 % CIs） by using Rev Man 5. 3 software. Results A total of 4 RCTs involving 8 751 patients were included. The results of meta-analysis showed that initiating ART at CD4^＋ T-cell counts（CD4 counts） ≥ 350 cells/μL or 500 cells/μL, comparing to deferring initiation of ART to CD4 counts 〈350 cells/μL, would benefit patients more：（ 1） Risk of AIDS-defining illnesses which representing disease progression, reduced significantly when starting ART at higher CD4 counts（no less than 350 cells/μL）（RR= 0. 49, 95 %CI 0. 38 to 0. 64, P〈0. 001）. The reduction of risk was even more significant when initiating ART at CD4 counts of not less than 500 cells/μL（RR= 0. 38, 95 %CI 0. 24 to 0. 59, P〈0. 001）.（ 2） When initiating ART at CD4 counts of not less than 350 cells/μL, the risk of serious non-AIDS related events was significantly reduced by 42 %（RR= 0. 58, 95 %CI 0. 40 to 0. 83, P= 0. 003）. When initiating ART at CD4 counts of not less than 500 cells/μL, according to START 2015, the risk of serious non-AIDS related events could be reduced by 39 %（RR= 0. 61, P= 0. 04）.（ 3） However, when initiating ART at CD4 counts of not less than 350 cells/μL or 500 cells/μL, comparing to deferring initiation, there were no statistically significant differences in death（RR= 0. 70, 95 %CI 0. 48 to 1. 02, P= 0. 06） and serious adverse events（RR= 0. 67, 95 %CI 0. 38 to 1. 20, P= 0. 18）. Conclusions Our findings contribute to the evidence base for recommending initiating ART at CD4 counts of 350- 500 cells/μL compared to initiating it later when CD4 counts fall below 350 cells/μL. As for patients with CD4 counts of not less than 500 cells/μL, initiation of ART is also recommended.
出处
《中国循证医学杂志》
CSCD
2016年第10期1137-1147,共11页
Chinese Journal of Evidence-based Medicine
基金
国家科技重大专项-传染病专项(编号:2012 ZX 0004901)
