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

Mathis S, Khanlari B, Pulido F, Schechter M, Negredo E, Nelson M, Vernazza P, Cahn P, Meynard JL, Arribas J, Bucher HC - PLoS ONE (2011)

Bottom Line: 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.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.

View Article: PubMed Central - PubMed

Affiliation: Basel Institute for Clinical Epidemiology and Biostatistics, University Hospital Basel, Basel, Switzerland.

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.

Show MeSH

Related in: MedlinePlus

Risk ratios for maintaining viral suppression, intention to treat analysis, 48 week follow-up, viral suppression <50 copies/ml.
© Copyright Policy
Related In: Results  -  Collection


getmorefigures.php?uid=PMC3139616&req=5

pone-0022003-g003: Risk ratios for maintaining viral suppression, intention to treat analysis, 48 week follow-up, viral suppression <50 copies/ml.

Mentions: In the intention to treat analysis, the summary risk ratio at 48 weeks of follow-up of PI/r monotherapy compared to cART for viral suppression as defined in individual trials was 0.96 ((95%CI 0.91 to 1.02) p = 0.18, p for heterogeneity 0.19, I2 = 27.6%; risk difference −0.04 (95%CI −0.09 to 0.02) p = 0.16, p for heterogeneity  = 0.08, I2 = 41.2%) (Figure 2 and Table S3). The respective risk ratios of PI/ monotherapy compared with cART for viral suppression with <50 copies/ml were 0.94 [(95% CI 0.89 to 1.00) p = 0.06 p for heterogeneity 0.17 I2 = 30.7%; risk difference −0.06 (95%CI -0.11 to 0) p = 0.05, p for heterogeneity  = 0.08, I2 = 43.1%] (Figure 3 and Table S3) and for viral suppression with <500 copies/ml 0.98 [(95%CI 0.93 to 1.03) p>0.20, p for heterogeneity 0.18, I2 = 29.9%; risk difference −0.02 (95%CI -0.08 to 0.03) p>0.20, p for heterogeneity  = 0.10, I2 = 39.6].


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

Mathis S, Khanlari B, Pulido F, Schechter M, Negredo E, Nelson M, Vernazza P, Cahn P, Meynard JL, Arribas J, Bucher HC - PLoS ONE (2011)

Risk ratios for maintaining viral suppression, intention to treat analysis, 48 week follow-up, viral suppression <50 copies/ml.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3139616&req=5

pone-0022003-g003: Risk ratios for maintaining viral suppression, intention to treat analysis, 48 week follow-up, viral suppression <50 copies/ml.
Mentions: In the intention to treat analysis, the summary risk ratio at 48 weeks of follow-up of PI/r monotherapy compared to cART for viral suppression as defined in individual trials was 0.96 ((95%CI 0.91 to 1.02) p = 0.18, p for heterogeneity 0.19, I2 = 27.6%; risk difference −0.04 (95%CI −0.09 to 0.02) p = 0.16, p for heterogeneity  = 0.08, I2 = 41.2%) (Figure 2 and Table S3). The respective risk ratios of PI/ monotherapy compared with cART for viral suppression with <50 copies/ml were 0.94 [(95% CI 0.89 to 1.00) p = 0.06 p for heterogeneity 0.17 I2 = 30.7%; risk difference −0.06 (95%CI -0.11 to 0) p = 0.05, p for heterogeneity  = 0.08, I2 = 43.1%] (Figure 3 and Table S3) and for viral suppression with <500 copies/ml 0.98 [(95%CI 0.93 to 1.03) p>0.20, p for heterogeneity 0.18, I2 = 29.9%; risk difference −0.02 (95%CI -0.08 to 0.03) p>0.20, p for heterogeneity  = 0.10, I2 = 39.6].

Bottom Line: 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.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.

View Article: PubMed Central - PubMed

Affiliation: Basel Institute for Clinical Epidemiology and Biostatistics, University Hospital Basel, Basel, Switzerland.

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.

Show MeSH
Related in: MedlinePlus