齐多夫定（AZT）与齐多夫定加去羟肌苷（ddI）以及齐多夫定加扎西他滨（ddC）用于HIV感染成人的比较

Zidovudine (AZT) versus AZT plus didanosine (ddI) versus AZT plus zalcitabine (ddC) in HIV infected adults.

作者信息

Darbyshire J, Foulkes M, Peto R, Duncan W, Babiker A, Collins R, Hughes M, Peto T, Walker A

机构信息

MRC Clinical Trials Unit, 222 Euston Road, London, UK, NW1 2DA.

出版信息

Cochrane Database Syst Rev. 2000;2000(2):CD002038. doi: 10.1002/14651858.CD002038.

DOI:10.1002/14651858.CD002038

PMID:10796851

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8406963/

Abstract

BACKGROUND

Zidovudine (AZT) monotherapy was the first antiretroviral drug to be tested widely. The next two drugs to be developed were didanosine (ddI) and zalcitabine (ddC).

OBJECTIVES

To assess the effects of zidovudine (AZT), zidovudine plus didanosine (ddI) and zidovudine plus zalcitabine (ddC) on HIV disease progression and survival.

SEARCH STRATEGY

Investigators and pharmaceutical companies were contacted, and MEDLINE searches were supplemented by searching conference abstracts.

SELECTION CRITERIA

Randomised controlled trials comparing any two of AZT plus ddI, AZT plus ddC or AZT alone in participants with or without AIDS which collected information on deaths and new AIDS events.

DATA COLLECTION AND ANALYSIS

Individual patient data with, wherever possible, follow-up obtained beyond that previously published were obtained and checked for internal consistency and consistency with any published reports; any apparent discrepancies were resolved with the trialists. Time to death and to disease progression (defined as a new AIDS-defining event or prior death) were analysed on an intention to treat basis, stratified to avoid direct comparisons between participants in different trials.

MAIN RESULTS

Six trials were included in the meta-analysis. During a median follow-up of 29 months, 2904 individuals progressed, of whom 1850 died. The addition of ddI to AZT delayed both progression (RR 0.74; 95% CI 0.67 to 0.82, P<0.0001) and death (RR 0.72; 95% CI 0.64 to 0.82, P<0.0001). Likewise, the addition of ddC to AZT also delayed progression (RR 0. 86; 95% CI 0.78 to 0.94, P=0.001) and death (RR 0.87; 95% CI 0.77 to 0.98, P=0.02). After 3 years the estimated percentages alive and without a new AIDS event were 53% for AZT+ddI, 49% for AZT+ddC and 44% for AZT alone; the percentages alive were 68%, 63% and 59% respectively. Five of the six trials involved randomised comparisons of AZT+ddI versus AZT+ddC: in these, the AZT+ddI regimen had greater effects on disease progression (P=0.004) and death (P=0.009).

REVIEWER'S CONCLUSIONS: The use of ddI and, to a lesser extent, ddC delayed both HIV disease progression and death, at least when added to AZT.

摘要

背景

齐多夫定（AZT）单药疗法是首个得到广泛测试的抗逆转录病毒药物。接下来研发的两种药物是去羟肌苷（ddI）和扎西他滨（ddC）。

目的

评估齐多夫定（AZT）、齐多夫定加去羟肌苷（ddI）以及齐多夫定加扎西他滨（ddC）对HIV疾病进展和生存的影响。

检索策略

联系了研究人员和制药公司，并通过检索会议摘要对MEDLINE搜索进行补充。

选择标准

比较AZT加ddI、AZT加ddC或单独使用AZT中的任意两种疗法的随机对照试验，试验对象为患有或未患有艾滋病的患者，且收集了死亡和新的艾滋病事件信息。

数据收集与分析

获取个体患者数据，并尽可能获得比之前发表的随访时间更长的数据，检查数据的内部一致性以及与任何已发表报告的一致性；任何明显差异都与试验人员进行了核对。对死亡时间和疾病进展时间（定义为新的艾滋病定义事件或先前死亡）进行意向性分析，进行分层以避免不同试验参与者之间的直接比较。

主要结果

六项试验纳入了荟萃分析。在中位随访29个月期间，2904人病情进展，其中1850人死亡。AZT加用ddI可延缓病情进展（风险比0.74；95%置信区间0.67至0.82，P<0.0001）和死亡（风险比0.72；95%置信区间0.64至0.82，P<0.0001）。同样，AZT加用ddC也可延缓病情进展（风险比0.86；95%置信区间0.78至0.94，P=0.001）和死亡（风险比0.87；95%置信区间0.77至0.98，P=0.02）。3年后，AZT+ddI组、AZT+ddC组和单独使用AZT组存活且无新的艾滋病事件的估计百分比分别为53%、49%和44%；存活百分比分别为68%、63%和59%。六项试验中的五项涉及AZT+ddI与AZT+ddC组的随机对照比较：在这些试验中，AZT+ddI方案对疾病进展（P=0.004）和死亡（P=0.009）的影响更大。