齐多夫定单用预防HIV母婴传播的有效性与安全性的系统评价

Effectiveness and Safety of Zidovudine for Preventing the Risk of Mother-to-Child Transmission of HIV:A Systematic Review

目的系统评价单独应用齐多夫定(zidovudine,ZDV)阻断HIV母婴传播的有效性和安全性。方法采用Cochrane系统评价方法,计算机检索Cochrane图书馆(2007第1期)、PubMed、EMbase、CINAHL、AIDSearch、AIDSLINE、AIDSTRIALS、AIDSDRUGS、AIDSinfo、CRD(center of review and dissemination)、CBMdisc,VIP和CNKI等数据库,以及全球或地区性AIDS相关的会议论文集、政府或非政府组织的相关文件等,检索日期截至2007年4月30日,全面收集全球抗艾滋病病毒药物预防HIV母婴传播的随机对照试验。由两名评价员独立筛查文献、评价质量和提取资料,然后交叉核对,若遇分歧则征求第三方意见讨论解决。使用RevMan软件进行Meta分析。结果共纳入8个RCT,包括24篇全文和13篇摘要,其方法学质量的Jadad评分≥3分。Meta分析显示:①ZDV与安慰剂比较共纳入4个RCTs(2385例),无论长短疗程、母乳或非母乳喂养人群,ZDV预防HIV母婴传播的效果均优于安慰剂组,降低HIV母婴传播风险43%～50%,且两组死产率、婴儿死亡率、母亲死亡率、早产、低体重儿、出生缺陷、母婴不良反应发生率和母亲产前、产时和产后并发症发生率差异均无统计学意义(P>0.05)。②1个大样本RCT(1437例)比较了ZDV不同疗程的效果,结果显示ZDV“长–长疗程”(从孕28周开始到产后6周)比“短–短疗程”(从孕35周开始到分娩后3天)降低HIV母婴传播风险61%[RR=0.39,95%CI(0.19,0.82)]。长–长疗程与长–短疗程(从孕28周开始到产后3天)及短-长疗程(从孕35周开始到产后6周)比较,其预防HIV母婴传播的效果差异均无统计学意义(P>0.05)。各组死产、新生儿死亡、1年内婴儿死亡、母亲死亡、早产、低体重儿、出生缺陷、母婴不良反应发生率相似(P>0.05)。③1个大样本RCT(1200例)显示:人工喂养+短程ZDV预防HIV母婴传播的效果优于母乳喂养+长程ZDV,可降低婴儿HIV感染风险的35%～39%,但提高了婴儿7个月时的死亡率(9.3%vs4.9%;P=0.003);两组婴儿早产率、低体重儿出生率、出生缺陷率、不良反应发生率相似(P>0.05)。④2个直接比较短程或超短程ZDV与单剂量奈韦拉平(Nevirapine,NVP)预防HIV母婴传播效果的RCT(702例)显示,NVP可降低HIV母婴传播风险的44%～48%,两组死产、6月内婴儿死亡、母亲死亡、低体重儿、母婴不良反应发生率相似(P>0.05)。结论无论长短疗程、母乳或非母乳喂养人群,ZDV预防HIV母婴传播的效果均优于安慰剂,且其妊娠结局和不良反应发生情况相似。ZDV“长–长疗程”比“短–短疗程”预防HIV母婴传播效果更好,但长–长疗程与长–短疗程、短–长疗程预防HIV母婴传播的效果相似;各组安全性相似。人工喂养+短程ZDV预防HIV母婴传播的效果优于母乳喂养+长程ZDV,但提高了婴儿7个月时的死亡率。单剂量NVP预防HIV母婴传播效果优于短程和超短程ZDV,且安全性相似。

Objective To assess the effectiveness and safety of zidovudine （ZDV） for preventing mother-to-child transmission （MTCT） of HIV. Methods A systematic review of randomized controlled trials （RCTs） was conducted using the methodology of The Cochrane Collaboration. PUBMED, EMBASE, CINAHL, AIDSearch, AIDSLINE, AIDSTRIALS, The Cochrane Library （Issue 1, 2007）,AIDSDRUGS, AIDSinfo, CRD （Center of Review and Dissemination） databases and three Chinese Databases （CBM, CNKI, VIP） were searched from establishment to 20 April,2007. We also searched the documents of government and non-governmental organizations （NGOs）, as well as the abstracts from relevant conferences, including the International AIDS Conferences, the annual Conference on Retroviruses and Opportunisticlnfections, etc. RCTs assessing the effects of ZDV for preventing MTCT were included. Trial selection, quality assessment and data extraction were done by two reviewers independently, with confirmation by cross-checking the information. Different opinions were resolved by discussion with a third party. Meta-analyses were conducted using The Cochrane Collaboration＇s RevMan 4.2.9 software. Results Eight original studies, involving 24 published articles and 13 conference abstracts were included. All included studies were of high quality with Jadad score of 3 or more. Our meta-analyses showed that： ①Based on four trials （2 385 participants）, any ZDV regimen （both long course and short course, either in breast-feeding population or not） significantly reduced the risk of mother-to-child transmission of HIV compared with placebo by 43%-50%. The incidences of stillbirth, infant mortality, maternal mortality, premature delivery, low birth weight, birth defects, adverse reactions （either in mothers or in children）, any antenatal, intrapartum or postpartum complication were comparable between ZDV and placebo （P〉0.05）. ② One trial （1 437 participants） compared different courses of ZDV. The ＂long-long＂ course （from 28 weeks in pregnancy for the mother and for the baby until 6 weeks old） decreased the risk of transmission by 61% （RR=0.39, 95%CI 0.19 to 0.82）, compared to the ＂short-short＂ course of ZDV （from 35 weeks in pregnancy for the mother and for the baby until 3 days old）. However, the effectiveness of the ＂long-short＂ course （from 28 weeks in pregnancy for the mother and for the baby until 3 days old） and the ＂short-long＂ course （from 35 weeks in pregnancy for the mother and for the baby until 6 weeks old） did not differ from that of the ＂long-long＂ course. There was no difference among the different courses of ZDV in the incidence of stillbirth, neonatal mortality, infant mortality within 1 year, maternal mortality, premature delivery, low birth weight, birth defects, and adverse reactions in mothers or children （P〉0.05）. ③ One trial （1 200 participants） compared formula-fed plus short course ZDV with breastfed plus long course ZDV. The formula-fed plus ZDV reduced the risk of transmission by 35%-39% in the period 7 months to 18 months after birth, and was associated with a higher mortality rate at 7 months than the breastfed plus ZDV group （9.3% vs. 4.9%; P=0.003）. The incidences of stillbirth, low birth weight, birth defect or adverse reaction （either in mothers or in children） were similar between the two groups （P〉0.05）. ④ Two RCTs （702 participants） showed that single dose nevirapine （sdNVP） given to mothers and babies was more effective than short course or ultra-short course regimens of ZDV （risk decreased by 44%-65%）. The incidences of stillbirth, infant and maternal mortality, low birth weight, and adverse reactions in mothers or children were similar between the two groups （P〉0.05）. Conclusions Compared withplacebo,any ZDV course （either long or short, either in breast-feeding population or not） was more effective in preventing MTCT of HIV with a similar safety profile. The ＂long-long＂ course ZDV decreased the risk of transmission, when compared with ＂short-short＂ course of ZDV, but the effectiveness and safety of ＂long-long＂ course, ＂long-short＂ course or ＂short-long＂ course of ZDV were similar. The formula-fed plus short course ZDV reduced the risk of transmission, and was associated with a higher mortality rate at 7 months compared with the breastfed plus long course ZDV after birth. Single dose nevirapine was more effective than short course or ultra-short course ZDV and had a similar safety profile.