Efficacy and safety of darunavir-ritonavir at week 48 in treatment-experienced patients with HIV-1 infection in POWER 1 and 2: a pooled subgroup analysis of data from two randomised trials

Bonaventura Clotet, Nicholas Bellos, Jean Michel Molina, David Cooper, Jean Christophe Goffard, Adriano Lazzarin, Andrej Wöhrmann, Christine Katlama, Timothy Wilkin, Richard Haubrich, Calvin Cohen, Charles Farthing, Dushyantha T Jayaweera, Martin Markowitz, Peter Ruane, Sabrina Spinosa-Guzman, Eric Lefebvre

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Abstract

Background: The continuing, randomised, multinational, phase IIB POWER 1 and 2 studies aim to evaluate efficacy and safety of darunavir in combination with low-dose ritonavir in treatment-experienced HIV-1-infected patients. We did a pooled subgroup analysis to update results at week 48 for patients receiving the recommended dose of darunavir-ritonavir compared with those receiving other protease inhibitors (PIs). Methods: After 24-week dose-finding phases and primary efficacy analyses, patients randomised to receive darunavir-ritonavir were given 600/100 mg twice daily, and patients receiving control PIs continued on assigned treatment into the longer-term, open-label phase; all patients continued on optimised background regimen. We assessed patients who had reached week 48 or discontinued earlier at the time of analysis; for the darunavir-ritonavir group, only patients who received 600/100 mg twice daily from baseline were included. Analyses were intention-to-treat. The POWER 2 study (TMC114-C202) is registered with ClinicalTrials.gov (NCT00071097). Findings: At week 48, 67 of 110 (61%) darunavir-ritonavir patients compared with 18 of 120 (15%) of control PI patients had viral load reductions of 1 log10 copies per mL or greater from baseline (primary endpoint; difference in response rates 46%, 95% CI 35%-57%, p<0·0001). Based on a logistic regression model including stratification factors (baseline number of primary PI mutations, use of enfuvirtide, baseline viral load) and study as covariates, the difference in response was 50% (odds ratio 11·72, 95% CI 5·75-23·89). In the darunavir-ritonavir group, rates of adverse events were mostly lower than or similar to those in the control group when corrected for treatment exposure. No unexpected safety concerns were identified. Interpretation: Efficacy responses with darunavir-ritonavir 600/100 mg twice daily plus optimised background regimen were greater than those with control PI and were sustained to at least week 48, with favourable safety and tolerability in treatment-experienced patients. This regimen could expand the treatment options available for such patients.

Original languageEnglish
Pages (from-to)1169-1178
Number of pages10
JournalLancet
Volume369
Issue number9568
DOIs
StatePublished - Apr 7 2007

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Ritonavir
HIV Infections
HIV-1
Safety
Protease Inhibitors
Therapeutics
Viral Load
Darunavir
Logistic Models
Intention to Treat Analysis
Odds Ratio

ASJC Scopus subject areas

  • Medicine(all)

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Efficacy and safety of darunavir-ritonavir at week 48 in treatment-experienced patients with HIV-1 infection in POWER 1 and 2 : a pooled subgroup analysis of data from two randomised trials. / Clotet, Bonaventura; Bellos, Nicholas; Molina, Jean Michel; Cooper, David; Goffard, Jean Christophe; Lazzarin, Adriano; Wöhrmann, Andrej; Katlama, Christine; Wilkin, Timothy; Haubrich, Richard; Cohen, Calvin; Farthing, Charles; Jayaweera, Dushyantha T; Markowitz, Martin; Ruane, Peter; Spinosa-Guzman, Sabrina; Lefebvre, Eric.

In: Lancet, Vol. 369, No. 9568, 07.04.2007, p. 1169-1178.

Research output: Contribution to journalArticle

Clotet, B, Bellos, N, Molina, JM, Cooper, D, Goffard, JC, Lazzarin, A, Wöhrmann, A, Katlama, C, Wilkin, T, Haubrich, R, Cohen, C, Farthing, C, Jayaweera, DT, Markowitz, M, Ruane, P, Spinosa-Guzman, S & Lefebvre, E 2007, 'Efficacy and safety of darunavir-ritonavir at week 48 in treatment-experienced patients with HIV-1 infection in POWER 1 and 2: a pooled subgroup analysis of data from two randomised trials', Lancet, vol. 369, no. 9568, pp. 1169-1178. https://doi.org/10.1016/S0140-6736(07)60497-8
Clotet, Bonaventura ; Bellos, Nicholas ; Molina, Jean Michel ; Cooper, David ; Goffard, Jean Christophe ; Lazzarin, Adriano ; Wöhrmann, Andrej ; Katlama, Christine ; Wilkin, Timothy ; Haubrich, Richard ; Cohen, Calvin ; Farthing, Charles ; Jayaweera, Dushyantha T ; Markowitz, Martin ; Ruane, Peter ; Spinosa-Guzman, Sabrina ; Lefebvre, Eric. / Efficacy and safety of darunavir-ritonavir at week 48 in treatment-experienced patients with HIV-1 infection in POWER 1 and 2 : a pooled subgroup analysis of data from two randomised trials. In: Lancet. 2007 ; Vol. 369, No. 9568. pp. 1169-1178.
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abstract = "Background: The continuing, randomised, multinational, phase IIB POWER 1 and 2 studies aim to evaluate efficacy and safety of darunavir in combination with low-dose ritonavir in treatment-experienced HIV-1-infected patients. We did a pooled subgroup analysis to update results at week 48 for patients receiving the recommended dose of darunavir-ritonavir compared with those receiving other protease inhibitors (PIs). Methods: After 24-week dose-finding phases and primary efficacy analyses, patients randomised to receive darunavir-ritonavir were given 600/100 mg twice daily, and patients receiving control PIs continued on assigned treatment into the longer-term, open-label phase; all patients continued on optimised background regimen. We assessed patients who had reached week 48 or discontinued earlier at the time of analysis; for the darunavir-ritonavir group, only patients who received 600/100 mg twice daily from baseline were included. Analyses were intention-to-treat. The POWER 2 study (TMC114-C202) is registered with ClinicalTrials.gov (NCT00071097). Findings: At week 48, 67 of 110 (61{\%}) darunavir-ritonavir patients compared with 18 of 120 (15{\%}) of control PI patients had viral load reductions of 1 log10 copies per mL or greater from baseline (primary endpoint; difference in response rates 46{\%}, 95{\%} CI 35{\%}-57{\%}, p<0·0001). Based on a logistic regression model including stratification factors (baseline number of primary PI mutations, use of enfuvirtide, baseline viral load) and study as covariates, the difference in response was 50{\%} (odds ratio 11·72, 95{\%} CI 5·75-23·89). In the darunavir-ritonavir group, rates of adverse events were mostly lower than or similar to those in the control group when corrected for treatment exposure. No unexpected safety concerns were identified. Interpretation: Efficacy responses with darunavir-ritonavir 600/100 mg twice daily plus optimised background regimen were greater than those with control PI and were sustained to at least week 48, with favourable safety and tolerability in treatment-experienced patients. This regimen could expand the treatment options available for such patients.",
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T1 - Efficacy and safety of darunavir-ritonavir at week 48 in treatment-experienced patients with HIV-1 infection in POWER 1 and 2

T2 - a pooled subgroup analysis of data from two randomised trials

AU - Clotet, Bonaventura

AU - Bellos, Nicholas

AU - Molina, Jean Michel

AU - Cooper, David

AU - Goffard, Jean Christophe

AU - Lazzarin, Adriano

AU - Wöhrmann, Andrej

AU - Katlama, Christine

AU - Wilkin, Timothy

AU - Haubrich, Richard

AU - Cohen, Calvin

AU - Farthing, Charles

AU - Jayaweera, Dushyantha T

AU - Markowitz, Martin

AU - Ruane, Peter

AU - Spinosa-Guzman, Sabrina

AU - Lefebvre, Eric

PY - 2007/4/7

Y1 - 2007/4/7

N2 - Background: The continuing, randomised, multinational, phase IIB POWER 1 and 2 studies aim to evaluate efficacy and safety of darunavir in combination with low-dose ritonavir in treatment-experienced HIV-1-infected patients. We did a pooled subgroup analysis to update results at week 48 for patients receiving the recommended dose of darunavir-ritonavir compared with those receiving other protease inhibitors (PIs). Methods: After 24-week dose-finding phases and primary efficacy analyses, patients randomised to receive darunavir-ritonavir were given 600/100 mg twice daily, and patients receiving control PIs continued on assigned treatment into the longer-term, open-label phase; all patients continued on optimised background regimen. We assessed patients who had reached week 48 or discontinued earlier at the time of analysis; for the darunavir-ritonavir group, only patients who received 600/100 mg twice daily from baseline were included. Analyses were intention-to-treat. The POWER 2 study (TMC114-C202) is registered with ClinicalTrials.gov (NCT00071097). Findings: At week 48, 67 of 110 (61%) darunavir-ritonavir patients compared with 18 of 120 (15%) of control PI patients had viral load reductions of 1 log10 copies per mL or greater from baseline (primary endpoint; difference in response rates 46%, 95% CI 35%-57%, p<0·0001). Based on a logistic regression model including stratification factors (baseline number of primary PI mutations, use of enfuvirtide, baseline viral load) and study as covariates, the difference in response was 50% (odds ratio 11·72, 95% CI 5·75-23·89). In the darunavir-ritonavir group, rates of adverse events were mostly lower than or similar to those in the control group when corrected for treatment exposure. No unexpected safety concerns were identified. Interpretation: Efficacy responses with darunavir-ritonavir 600/100 mg twice daily plus optimised background regimen were greater than those with control PI and were sustained to at least week 48, with favourable safety and tolerability in treatment-experienced patients. This regimen could expand the treatment options available for such patients.

AB - Background: The continuing, randomised, multinational, phase IIB POWER 1 and 2 studies aim to evaluate efficacy and safety of darunavir in combination with low-dose ritonavir in treatment-experienced HIV-1-infected patients. We did a pooled subgroup analysis to update results at week 48 for patients receiving the recommended dose of darunavir-ritonavir compared with those receiving other protease inhibitors (PIs). Methods: After 24-week dose-finding phases and primary efficacy analyses, patients randomised to receive darunavir-ritonavir were given 600/100 mg twice daily, and patients receiving control PIs continued on assigned treatment into the longer-term, open-label phase; all patients continued on optimised background regimen. We assessed patients who had reached week 48 or discontinued earlier at the time of analysis; for the darunavir-ritonavir group, only patients who received 600/100 mg twice daily from baseline were included. Analyses were intention-to-treat. The POWER 2 study (TMC114-C202) is registered with ClinicalTrials.gov (NCT00071097). Findings: At week 48, 67 of 110 (61%) darunavir-ritonavir patients compared with 18 of 120 (15%) of control PI patients had viral load reductions of 1 log10 copies per mL or greater from baseline (primary endpoint; difference in response rates 46%, 95% CI 35%-57%, p<0·0001). Based on a logistic regression model including stratification factors (baseline number of primary PI mutations, use of enfuvirtide, baseline viral load) and study as covariates, the difference in response was 50% (odds ratio 11·72, 95% CI 5·75-23·89). In the darunavir-ritonavir group, rates of adverse events were mostly lower than or similar to those in the control group when corrected for treatment exposure. No unexpected safety concerns were identified. Interpretation: Efficacy responses with darunavir-ritonavir 600/100 mg twice daily plus optimised background regimen were greater than those with control PI and were sustained to at least week 48, with favourable safety and tolerability in treatment-experienced patients. This regimen could expand the treatment options available for such patients.

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