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.
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-infectedpatients 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.
Authors: Heather J Ribaudo; Constance A Benson; Yu Zheng; Susan L Koletar; Ann C Collier; Judith J Lok; Marlene Smurzynski; Ronald J Bosch; Barbara Bastow; Jeffrey T Schouten Journal: Clin Infect Dis Date: 2011-04-01 Impact factor: 9.079
Authors: Laura K White; Jeong-Joong Yoon; Jin K Lee; Aiming Sun; Yuhong Du; Haian Fu; James P Snyder; Richard K Plemper Journal: Antimicrob Agents Chemother Date: 2007-04-30 Impact factor: 5.191
Authors: Lawrence Mbuagbaw; Sara Mursleen; James H Irlam; Alicen B Spaulding; George W Rutherford; Nandi Siegfried Journal: Cochrane Database Syst Rev Date: 2016-12-10
Authors: Stephen T Wright; Jennifer Hoy; Brian Mulhall; Catherine C Oʼconnor; Kathy Petoumenos; Timothy Read; Don Smith; Ian Woolley; Mark A Boyd Journal: J Acquir Immune Defic Syndr Date: 2014-05-01 Impact factor: 3.731