Intervention Review

Immediate versus deferred zidovudine (AZT) in asymptomatic or mildly symptomatic HIV infected adults

  1. Janet Darbyshire1,*,
  2. Mary Foulkes2,
  3. Richard Peto3,
  4. William Duncan4,
  5. Abdel Babiker1,
  6. Rory Collins5,
  7. Mike Hughes6,
  8. Tim EA Peto7,
  9. Sarah A Walker8

Editorial Group: Cochrane HIV/AIDS Group

Published Online: 17 MAR 2010

Assessed as up-to-date: 5 MAR 2000

DOI: 10.1002/14651858.CD002039

Database Title

Additional Information

How to Cite

Darbyshire J, Foulkes M, Peto R, Duncan W, Babiker A, Collins R, Hughes M, Peto TEA, Walker SA. Immediate versus deferred zidovudine (AZT) in asymptomatic or mildly symptomatic HIV infected adults. Cochrane Database of Systematic Reviews 2000, Issue 3. Art. No.: CD002039. DOI: 10.1002/14651858.CD002039.

Author Information

  1. 1

    London, UK

  2. 2

    FDA/CBER/OCD, Division of Biostatistics and Epidemiology, Rockville, USA

  3. 3

    University of Oxford, Clinical Trial Service and Epidemiological Studies Unit, Oxford, UK

  4. 4

    NIH, Division of AIDS, Therapeutics Research, Bethesda, USA

  5. 5

    ICRF Clinical Trial Service Unit, Oxford, UK

  6. 6

    Harvard School of Public Health, Department of Biostatistics, Boston, USA

  7. 7

    John Radcliffe Hospital, The Nuffield Department of Medicine, Oxford, UK

  8. 8

    MRC Clinical Trials Unit, HIV Division, London, UK

*Janet Darbyshire, MRC Clinical Trials Unit, 222 Euston Road, London, NW1 2DA, UK. j.darbyshire@ctu.mrc.ac.uk.

Publication History

  1. Publication Status: Stable (no update expected for reasons given in 'What's new')
  2. Published Online: 17 MAR 2010

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Abstract

  1. Top of page
  2. Abstract
  3. Plain language summary
  4. 摘要

Background

Zidovudine (AZT) monotherapy was the first antiretroviral drug to be tested widely. Subsequent trials in asymptomatic or early symptomatic HIV infection indicated short-term delays in disease progression with AZT, but not improved survival.

Objectives

To assess the effects of immediate versus deferred zidovudine (AZT) on HIV disease progression and survival.

Search methods

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

Selection criteria

Randomised controlled trials comparing immediate versus deferred AZT in participants without AIDS which prospectively collected deaths and new AIDS events.

Data collection and analysis

Individual patient data with, wherever possible, follow-up obtained beyond that previously published was 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

Nine trials were included in the meta-analysis. During a median follow-up of 50 months, 1908 individuals developed disease progression, of whom 1351 died. In the deferred group, 61% started antiretroviral therapy (median time to therapy 28 months, which was AZT monotherapy in 94%). During the first year of follow-up immediate AZT halved the rate of disease progression (P<0.0001), increasing the probability of AIDS-free survival at one year from 96% to 98%, but this early benefit did not persist: after 6 years AIDS-free survival was 54% in both groups, and at no time was there any difference in overall survival, which at 6 years was 64% with immediate and 65% with deferred AZT (rate ratio [RR] 1.04, 95% confidence interval [CI] 0.94 to 1.15).

Authors' conclusions

Although immediate use of AZT halved disease progression during the first year, this effect was not sustained, and there was no improvement in survival in the short or long term.

 

Plain language summary

  1. Top of page
  2. Abstract
  3. Plain language summary
  4. 摘要

While AZT slows down the progression of HIV disease in the short-term, the improvement does not last and it does not increase survival

Zidovudine (AZT) was the first antiretroviral drug used in HIV and AIDS. It is expensive and has several adverse effects including nausea, vomiting, blood problems (anaemia and neutropenia) and myopathy (muscle weakness). The review of trials found that AZT does delay the early progression of HIV disease, but this improvement is not sustained. AZT alone does not increase survival for people without AIDS.

 

摘要

  1. Top of page
  2. Abstract
  3. Plain language summary
  4. 摘要

背景

在無症狀或輕微症狀人類免疫不全病毒感染的成人，立即和延遲性使用 AZT 的比較

AZT是最早被廣泛單一使用的抗反轉錄病毒的藥物. 隨後的臨床試驗中指出，對於無症狀或早期輕微症狀人類免疫缺乏病毒感染的病人，有短期的延緩疾病進展的功效，但不能改善存活率。

目標

評估立即和延遲性使用 AZT 在治療無症狀或輕度症狀人類免疫缺乏病毒感染的病人的效果.

搜尋策略

資料搜尋方法包括了接觸研究人員和製藥公司，並搜尋會議摘要以補充MEDLINE搜尋。

選擇標準

以隨機對照試驗，針對未患有AIDS的參與者，比較立即或是延遲給予AZT，並個別收集死亡以及AIDS新感染事件。

資料收集與分析

取得個別病人資料以及(如果可以的話)之前所發表以外的後續追蹤。並且檢查內部一致性，以及是否與其他已發表的報告結果一致；如果遇到明顯差異之處，則由試驗者處理。 以治療意向為基礎分析直到死亡的時間以及病程(定義為新AIDS定義事件或是死亡之前)，使用分層分析以避免直接比較不同試驗的參與者。

主要結論

有9項臨床試驗被納入這次統合分析中。在追蹤期間中位數為50個月的期間中，1908個病人發展病程惡化，其中1351人死亡。在延遲使用AZT組，61％的病人開始抗反轉錄病毒治療(到治療中位數時間為28個月，而94％單只使用AZT治療)。在第一年的後續追蹤, 立即使用AZT組，對於延遲疾病惡化有統計學上的顯著意義(P值<0.0001)，增加的一年內免於愛滋病機率從96％升至98％，但這個早期的幫助並沒有持續兩組在於6年免於愛滋病率皆為54 ％，在兩個組別，存活率上也無差異，6年存活率在立即組為64%, 延遲組為65%(機率比為1.04, 95％的信賴區間為0.94至1.15).

作者結論

雖然立即使用AZT減少疾病在第一年期間的惡化，但這個效果是不會持久，也對於短與長期存活率也無改善。

翻譯人

本摘要由臺北榮民總醫院賴志泓翻譯。

此翻譯計畫由臺灣國家衛生研究院(National Health Research Institutes, Taiwan)統籌。

總結

即使AZT可減緩人類免疫不全病毒感染的疾病的病程在短期的進展，但效果並不會長期持續且對存活率亦無改善。 survivalzidovudine(AZT)是第一個抗反轉錄病毒藥物，用來治療人類免疫缺乏病毒感染和愛滋病。它非常昂貴，而且有些副作用，包括噁心，嘔吐，血液的問題(如貧血和中性球低下)和肌肉病變(肌肉無力)。這篇文章，回顧多個臨床試驗, 發現AZT對於減少疾病在第一年期間的惡化有幫助，但這個效果是不會持久。且單獨使用 AZT於無愛滋病的病人, 在存活率上也無改善。

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