Effectiveness of protease inhibitor monotherapy versus combination antiretroviral maintenance therapy: A meta-analysis
Entity
UAM. Departamento de MedicinaPublisher
Public Library of ScienceDate
2011-07-22Citation
10.1371/journal.pone.0022003
Plos One 6.7 (2011): e22003
ISSN
1932-6203 (online)DOI
10.1371/journal.pone.0022003Funded by
Heiner C. Bucher is supported by grants from santésuisse, the Gottfried and Julia Bangerter-Rhyner-Foundation. Abbott Switzerland supported the Basel Institute for Clinical Epidemiology and Biostatistics with an unrestricted grant for clinical HIV researchSubjects
Drug Therapy; HIV Infections; Maintenance Chemotherapy; Risk Factors; Clinical Trials as Topic; MedicinaRights
© 2011 Mathis et al.Abstract
Background: The unparalleled success of combination antiretroviral therapy (cART) is based on the combination of three drugs from two classes. There is insufficient evidence whether simplification to ritonavir boosted protease inhibitor (PI/r) monotherapy in virologically suppressed HIV-infected patients is effective and safe to reduce cART side effects and costs. Methods: We systematically searched Medline, Embase, the Cochrane Library, conference proceedings and trial registries to identify all randomised controlled trials comparing PI/r monotherapy to cART in suppressed patients. We calculated in an intention to treat (loss-of follow-up, discontinuation of assigned drugs equals failure) and per-protocol analysis (exclusion of protocol violators following randomisation) and based on three different definitions for virological failure pooled risk ratios for remaining virologically suppressed. Findings: We identified 10 trials comparing 3 different PIs with cART based on a PI/r plus 2 reverse transcriptase inhibitors in 1189 patients. With the most conservative approach (viral load <50 copies/ml on two consecutive measurements), the risk ratios for viral suppression at 48 weeks of PI/r monotherapy compared to cART were in the ITT analysis 0.94 8 (95% CI 0.89 to 1.00) p = 0.06; risk difference -0.06 (95%CI -0.11 to 0) p = 0.05, p for heterogeneity = 0.08, I 2 = 43.1%) and in the PP analysis 0.93 ((95%CI 0.90 to 0.97) p<0.001; risk difference -0.07 (95%CI -0.10 to -0.03) p<0.001, p for heterogeneity = 0.44, I 2 = 0%). Reintroduction of cART in 44 patients with virological failure led in 93% to de-novo viral suppression. Interpretation: Virologically well suppressed HIV-infected patients have a lower chance to maintain viral suppression when switching from cART to PI/r monotherapy. Failing patients achieve high rates of de-novo viral suppression following reintroduction of reverse transcriptase inhibitors
Files in this item
Google Scholar:Mathis, Sandra
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Khanlari, Bettina
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Pulido, Federico
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Schechter, Martin T.
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Negredo, Eugènia
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Nelson, Mark Richard
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Vernazza, Pietro Luigi
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Cahn, Pedro E.
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Meynard -, Jean Luc
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Arribas, José Ramón
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Bucher, Heíner Claudins
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