Immediate versus deferred zidovudine (AZT) in asymptomatic or mildly symptomatic HIV infected adults.
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...
| Principais autores: | , , , , , , , , |
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| Formato: | Journal article |
| Idioma: | English |
| Publicado em: |
2000
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| _version_ | 1826264085725970432 |
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| author | Darbyshire, J Foulkes, M Peto, R Duncan, W Babiker, A Collins, R Hughes, M Peto, T Walker, A |
| author_facet | Darbyshire, J Foulkes, M Peto, R Duncan, W Babiker, A Collins, R Hughes, M Peto, T Walker, A |
| author_sort | Darbyshire, J |
| collection | OXFORD |
| description | 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 STRATEGY: 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). REVIEWER'S 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. |
| first_indexed | 2024-03-06T20:02:07Z |
| format | Journal article |
| id | oxford-uuid:27aa5830-d5fa-4aea-b5be-ff0f4ad16a0f |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-06T20:02:07Z |
| publishDate | 2000 |
| record_format | dspace |
| spelling | oxford-uuid:27aa5830-d5fa-4aea-b5be-ff0f4ad16a0f2022-03-26T12:08:15ZImmediate versus deferred zidovudine (AZT) in asymptomatic or mildly symptomatic HIV infected adults.Journal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:27aa5830-d5fa-4aea-b5be-ff0f4ad16a0fEnglishSymplectic Elements at Oxford2000Darbyshire, JFoulkes, MPeto, RDuncan, WBabiker, ACollins, RHughes, MPeto, TWalker, A 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 STRATEGY: 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). REVIEWER'S 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. |
| spellingShingle | Darbyshire, J Foulkes, M Peto, R Duncan, W Babiker, A Collins, R Hughes, M Peto, T Walker, A Immediate versus deferred zidovudine (AZT) in asymptomatic or mildly symptomatic HIV infected adults. |
| title | Immediate versus deferred zidovudine (AZT) in asymptomatic or mildly symptomatic HIV infected adults. |
| title_full | Immediate versus deferred zidovudine (AZT) in asymptomatic or mildly symptomatic HIV infected adults. |
| title_fullStr | Immediate versus deferred zidovudine (AZT) in asymptomatic or mildly symptomatic HIV infected adults. |
| title_full_unstemmed | Immediate versus deferred zidovudine (AZT) in asymptomatic or mildly symptomatic HIV infected adults. |
| title_short | Immediate versus deferred zidovudine (AZT) in asymptomatic or mildly symptomatic HIV infected adults. |
| title_sort | immediate versus deferred zidovudine azt in asymptomatic or mildly symptomatic hiv infected adults |
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