Initial highly-active antiretroviral therapy with a protease inhibitor versus a non-nucleoside reverse transcriptase inhibitor: discrepancies between direct and indirect meta-analyses

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Abstract

Background: The optimum treatment choice between initial highly-active antiretroviral therapy (HAART) with a protease inhibitor (PI) versus a non-nucleoside reverse transcriptase inhibitor (NNRTI) is uncertain. An indirect analysis reported that PI-based HAART was better than NNRTI-based HAART. However, direct evidence for competing interventions is deemed more reliable than indirect evidence for making treatment decisions. We did a meta-analysis of head-to-head trials and compared the results with those of indirect analyses. Methods: 12 trials of at least 24 weeks' duration directly compared NNRTI-based versus PI-based HAART in HIV-infected patients with limited or no previous exposure to antiretrovirals. We also identified six trials of NNRTI-based HAART and eight trials of PI-based HAART, each versus two NRTI regimens. We analysed the outcomes of virological suppression, death or disease progression, and withdrawals due to adverse events. Findings: In the direct meta-analysis, NNRTI-based regimens were better than PI-based regimens for virological suppression (OR 1·60, 95% CI 1·31-1·96). The difference was reduced in higher-quality trials, but still favoured NNRTI-based HAART. There were no differences in death or disease progression (0·87, 0·56-1·35) or withdrawal because of adverse events (0·68, 0·43-1·08). By contrast, in indirect analyses NNRTI-based HAART was worse than PI-based HAART for virological suppression (0·26, 0·07-0·91). There were no significant differences for death or disease progression (1·28, 0·56-2·94) and withdrawals because of adverse events (1·46, 0·66-3·24). When trials of delavirdine were excluded, similar results were produced. Interpretation: Results from direct analyses suggested that NNRTI-based HAART was more effective than PI-based HAART for virological suppression and was similar to PI-based HAART for clinical outcomes. Indirect comparisons could be unreliable for complex and rapidly evolving interventions such as HAART.

Original languageEnglish (US)
Pages (from-to)1503-1515
Number of pages13
JournalLancet
Volume368
Issue number9546
DOIs
StatePublished - Oct 28 2006

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Reverse Transcriptase Inhibitors
Highly Active Antiretroviral Therapy
Protease Inhibitors
Meta-Analysis
Disease Progression
Delavirdine
Decision Making

ASJC Scopus subject areas

  • Medicine(all)

Cite this

@article{817b2759e96a4383a0a890b02cd64f86,
title = "Initial highly-active antiretroviral therapy with a protease inhibitor versus a non-nucleoside reverse transcriptase inhibitor: discrepancies between direct and indirect meta-analyses",
abstract = "Background: The optimum treatment choice between initial highly-active antiretroviral therapy (HAART) with a protease inhibitor (PI) versus a non-nucleoside reverse transcriptase inhibitor (NNRTI) is uncertain. An indirect analysis reported that PI-based HAART was better than NNRTI-based HAART. However, direct evidence for competing interventions is deemed more reliable than indirect evidence for making treatment decisions. We did a meta-analysis of head-to-head trials and compared the results with those of indirect analyses. Methods: 12 trials of at least 24 weeks' duration directly compared NNRTI-based versus PI-based HAART in HIV-infected patients with limited or no previous exposure to antiretrovirals. We also identified six trials of NNRTI-based HAART and eight trials of PI-based HAART, each versus two NRTI regimens. We analysed the outcomes of virological suppression, death or disease progression, and withdrawals due to adverse events. Findings: In the direct meta-analysis, NNRTI-based regimens were better than PI-based regimens for virological suppression (OR 1·60, 95{\%} CI 1·31-1·96). The difference was reduced in higher-quality trials, but still favoured NNRTI-based HAART. There were no differences in death or disease progression (0·87, 0·56-1·35) or withdrawal because of adverse events (0·68, 0·43-1·08). By contrast, in indirect analyses NNRTI-based HAART was worse than PI-based HAART for virological suppression (0·26, 0·07-0·91). There were no significant differences for death or disease progression (1·28, 0·56-2·94) and withdrawals because of adverse events (1·46, 0·66-3·24). When trials of delavirdine were excluded, similar results were produced. Interpretation: Results from direct analyses suggested that NNRTI-based HAART was more effective than PI-based HAART for virological suppression and was similar to PI-based HAART for clinical outcomes. Indirect comparisons could be unreliable for complex and rapidly evolving interventions such as HAART.",
author = "Roger Chou and Fu, {Rongwei (Rochelle)} and {Hoyt Huffman}, Laurie and Korthuis, {Philip (Todd)}",
year = "2006",
month = "10",
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doi = "10.1016/S0140-6736(06)69638-4",
language = "English (US)",
volume = "368",
pages = "1503--1515",
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number = "9546",

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T1 - Initial highly-active antiretroviral therapy with a protease inhibitor versus a non-nucleoside reverse transcriptase inhibitor

T2 - discrepancies between direct and indirect meta-analyses

AU - Chou, Roger

AU - Fu, Rongwei (Rochelle)

AU - Hoyt Huffman, Laurie

AU - Korthuis, Philip (Todd)

PY - 2006/10/28

Y1 - 2006/10/28

N2 - Background: The optimum treatment choice between initial highly-active antiretroviral therapy (HAART) with a protease inhibitor (PI) versus a non-nucleoside reverse transcriptase inhibitor (NNRTI) is uncertain. An indirect analysis reported that PI-based HAART was better than NNRTI-based HAART. However, direct evidence for competing interventions is deemed more reliable than indirect evidence for making treatment decisions. We did a meta-analysis of head-to-head trials and compared the results with those of indirect analyses. Methods: 12 trials of at least 24 weeks' duration directly compared NNRTI-based versus PI-based HAART in HIV-infected patients with limited or no previous exposure to antiretrovirals. We also identified six trials of NNRTI-based HAART and eight trials of PI-based HAART, each versus two NRTI regimens. We analysed the outcomes of virological suppression, death or disease progression, and withdrawals due to adverse events. Findings: In the direct meta-analysis, NNRTI-based regimens were better than PI-based regimens for virological suppression (OR 1·60, 95% CI 1·31-1·96). The difference was reduced in higher-quality trials, but still favoured NNRTI-based HAART. There were no differences in death or disease progression (0·87, 0·56-1·35) or withdrawal because of adverse events (0·68, 0·43-1·08). By contrast, in indirect analyses NNRTI-based HAART was worse than PI-based HAART for virological suppression (0·26, 0·07-0·91). There were no significant differences for death or disease progression (1·28, 0·56-2·94) and withdrawals because of adverse events (1·46, 0·66-3·24). When trials of delavirdine were excluded, similar results were produced. Interpretation: Results from direct analyses suggested that NNRTI-based HAART was more effective than PI-based HAART for virological suppression and was similar to PI-based HAART for clinical outcomes. Indirect comparisons could be unreliable for complex and rapidly evolving interventions such as HAART.

AB - Background: The optimum treatment choice between initial highly-active antiretroviral therapy (HAART) with a protease inhibitor (PI) versus a non-nucleoside reverse transcriptase inhibitor (NNRTI) is uncertain. An indirect analysis reported that PI-based HAART was better than NNRTI-based HAART. However, direct evidence for competing interventions is deemed more reliable than indirect evidence for making treatment decisions. We did a meta-analysis of head-to-head trials and compared the results with those of indirect analyses. Methods: 12 trials of at least 24 weeks' duration directly compared NNRTI-based versus PI-based HAART in HIV-infected patients with limited or no previous exposure to antiretrovirals. We also identified six trials of NNRTI-based HAART and eight trials of PI-based HAART, each versus two NRTI regimens. We analysed the outcomes of virological suppression, death or disease progression, and withdrawals due to adverse events. Findings: In the direct meta-analysis, NNRTI-based regimens were better than PI-based regimens for virological suppression (OR 1·60, 95% CI 1·31-1·96). The difference was reduced in higher-quality trials, but still favoured NNRTI-based HAART. There were no differences in death or disease progression (0·87, 0·56-1·35) or withdrawal because of adverse events (0·68, 0·43-1·08). By contrast, in indirect analyses NNRTI-based HAART was worse than PI-based HAART for virological suppression (0·26, 0·07-0·91). There were no significant differences for death or disease progression (1·28, 0·56-2·94) and withdrawals because of adverse events (1·46, 0·66-3·24). When trials of delavirdine were excluded, similar results were produced. Interpretation: Results from direct analyses suggested that NNRTI-based HAART was more effective than PI-based HAART for virological suppression and was similar to PI-based HAART for clinical outcomes. Indirect comparisons could be unreliable for complex and rapidly evolving interventions such as HAART.

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