Effectiveness of protease inhibitor monotherapy versus combination antiretroviral maintenance therapy: a meta-analysis.

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 eff...

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Main Authors: Sandra Mathis, Bettina Khanlari, Federico Pulido, Mauro Schechter, Eugenia Negredo, Mark Nelson, Pietro Vernazza, Pedro Cahn, Jean-Luc Meynard, Jose Arribas, Heiner C Bucher
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2011-01-01
Series:PLoS ONE
Online Access:http://europepmc.org/articles/PMC3139616?pdf=render
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spelling doaj-8d6eb2637fe741c2bfaac7a8a4cca16c2020-11-25T01:42:23ZengPublic Library of Science (PLoS)PLoS ONE1932-62032011-01-0167e2200310.1371/journal.pone.0022003Effectiveness of protease inhibitor monotherapy versus combination antiretroviral maintenance therapy: a meta-analysis.Sandra MathisBettina KhanlariFederico PulidoMauro SchechterEugenia NegredoMark NelsonPietro VernazzaPedro CahnJean-Luc MeynardJose ArribasHeiner C BucherThe 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.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.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.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.http://europepmc.org/articles/PMC3139616?pdf=render
collection DOAJ
language English
format Article
sources DOAJ
author Sandra Mathis
Bettina Khanlari
Federico Pulido
Mauro Schechter
Eugenia Negredo
Mark Nelson
Pietro Vernazza
Pedro Cahn
Jean-Luc Meynard
Jose Arribas
Heiner C Bucher
spellingShingle Sandra Mathis
Bettina Khanlari
Federico Pulido
Mauro Schechter
Eugenia Negredo
Mark Nelson
Pietro Vernazza
Pedro Cahn
Jean-Luc Meynard
Jose Arribas
Heiner C Bucher
Effectiveness of protease inhibitor monotherapy versus combination antiretroviral maintenance therapy: a meta-analysis.
PLoS ONE
author_facet Sandra Mathis
Bettina Khanlari
Federico Pulido
Mauro Schechter
Eugenia Negredo
Mark Nelson
Pietro Vernazza
Pedro Cahn
Jean-Luc Meynard
Jose Arribas
Heiner C Bucher
author_sort Sandra Mathis
title Effectiveness of protease inhibitor monotherapy versus combination antiretroviral maintenance therapy: a meta-analysis.
title_short Effectiveness of protease inhibitor monotherapy versus combination antiretroviral maintenance therapy: a meta-analysis.
title_full Effectiveness of protease inhibitor monotherapy versus combination antiretroviral maintenance therapy: a meta-analysis.
title_fullStr Effectiveness of protease inhibitor monotherapy versus combination antiretroviral maintenance therapy: a meta-analysis.
title_full_unstemmed Effectiveness of protease inhibitor monotherapy versus combination antiretroviral maintenance therapy: a meta-analysis.
title_sort effectiveness of protease inhibitor monotherapy versus combination antiretroviral maintenance therapy: a meta-analysis.
publisher Public Library of Science (PLoS)
series PLoS ONE
issn 1932-6203
publishDate 2011-01-01
description 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.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.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.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.
url http://europepmc.org/articles/PMC3139616?pdf=render
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