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Once-daily atazanavir/ritonavir versus twice-daily lopinavir/ritonavir, each in combination with tenofovir and emtricitabine, for management of antiretroviral-naive HIV-1-infected patients: 48 week efficacy and safety results of the CASTLE study

Summary Background Atazanavir/ritonavir is as effective as lopinavir/ritonavir, with a more favourable lipid profile and less gastrointestinal toxicity, in treatment-experienced HIV-1-infected patients. We compared these two combinations directly in treatment-naive patients. Methods In this open-lab... Full description

Journal Title: The Lancet (British edition) 2008, Vol.372 (9639), p.646-655
Main Author: Molina, Jean-Michel, Prof
Other Authors: Andrade-Villanueva, Jaime, MD , Echevarria, Juan, MD , Chetchotisakd, Ploenchan, Prof , Corral, Jorge, MD , David, Neal, FCFP [SA] , Moyle, Graeme, MD , Mancini, Marco, BS , Percival, Lisa, MS , Yang, Rong, PhD , Thiry, Alexandra, PhD , McGrath, Donnie, MD
Format: Electronic Article Electronic Article
Language: English
Subjects:
HIV
Quelle: Alma/SFX Local Collection
Publisher: England: Elsevier Ltd
ID: ISSN: 0140-6736
Link: https://www.ncbi.nlm.nih.gov/pubmed/18722869
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title: Once-daily atazanavir/ritonavir versus twice-daily lopinavir/ritonavir, each in combination with tenofovir and emtricitabine, for management of antiretroviral-naive HIV-1-infected patients: 48 week efficacy and safety results of the CASTLE study
format: Article
creator:
  • Molina, Jean-Michel, Prof
  • Andrade-Villanueva, Jaime, MD
  • Echevarria, Juan, MD
  • Chetchotisakd, Ploenchan, Prof
  • Corral, Jorge, MD
  • David, Neal, FCFP [SA]
  • Moyle, Graeme, MD
  • Mancini, Marco, BS
  • Percival, Lisa, MS
  • Yang, Rong, PhD
  • Thiry, Alexandra, PhD
  • McGrath, Donnie, MD
subjects:
  • Adult
  • Aged
  • Antiretroviral drugs
  • Atazanavir Sulfate
  • Clinical medicine
  • Drug Administration Schedule
  • Drug therapy
  • Drug Therapy, Combination
  • Female
  • Heart attacks
  • HIV
  • HIV Infections - drug therapy
  • HIV Protease Inhibitors - administration & dosage
  • HIV Protease Inhibitors - adverse effects
  • HIV Protease Inhibitors - therapeutic use
  • HIV-1
  • Human immunodeficiency virus
  • Humans
  • Internal Medicine
  • Lopinavir
  • Male
  • Middle Aged
  • Mortality
  • Oligopeptides - administration & dosage
  • Oligopeptides - adverse effects
  • Oligopeptides - therapeutic use
  • Patients
  • Pyridines - administration & dosage
  • Pyridines - adverse effects
  • Pyridines - therapeutic use
  • Pyrimidinones - administration & dosage
  • Pyrimidinones - adverse effects
  • Pyrimidinones - therapeutic use
  • Ritonavir - administration & dosage
  • Ritonavir - adverse effects
  • Ritonavir - therapeutic use
  • Sample size
  • Studies
  • Viral Load
ispartof: The Lancet (British edition), 2008, Vol.372 (9639), p.646-655
description: Summary Background Atazanavir/ritonavir is as effective as lopinavir/ritonavir, with a more favourable lipid profile and less gastrointestinal toxicity, in treatment-experienced HIV-1-infected patients. We compared these two combinations directly in treatment-naive patients. Methods In this open-label, international non-inferiority study, 883 antiretroviral-naive, HIV-1-infected patients were randomly assigned to receive atazanavir/ritonavir 300/100 mg once daily (n=440) or lopinavir/ritonavir 400/100 mg twice daily (n=443), in combination with fixed-dose tenofovir/emtricitabine 300/200 mg once daily. Randomisation was done with a computer-generated centralised randomisation schedule and was stratified by baseline levels of HIV RNA (viral load) and geographic region. The primary endpoint was the proportion of patients with viral load less than 50 copies per mL at week 48. The main efficacy analysis was done by intention to treat. This trial is registered with ClinicalTrials.gov , number NCT00272779. Findings At week 48, 343 (78%) of 440 patients receiving atazanavir/ritonavir and 338 (76%) of 443 patients receiving lopinavir/ritonavir had achieved a viral load of less than 50 copies per mL (difference 1·7%, 95% CI −3·8 to 7·1). Mean increases from baseline in CD4 cell count were similar (203 cells per μL in the atazanavir/ritonavir group vs 219 cells per μL in the lopinavir/ritonavir group). 25 (6%) patients in the atazanavir/ritonavir group and 26 (6%) in the lopinavir/ritonavir group were virological failures by week 48. Only two patients, both in the atazanavir/ritonavir group, had non-polymorphic protease inhibitor resistance mutations emerge on treatment, which conferred phenotypic resistance to atazanavir in one patient. Serious adverse events were noted in 51 (12%) of 441 patients in the atazanavir/ritonavir group and in 42 (10%) of 437 patients in the lopinavir/ritonavir group. Fewer patients in the atazanavir/ritonavir group than in the lopinavir/ritonavir group experienced grade 2–4 treatment-related diarrhoea (10 [2%] vs 50 [11%]) and nausea (17 [4%] vs 33 [8%]). Grade 2–4 jaundice was seen in 16 (4%) of 441 patients in the atazanavir/ritonavir group versus none of 437 patients in the lopinavir/ritonavir group; grade 3–4 increases in total bilirubin were seen in 146 (34%) of 435 patients on atazanavir/ritonavir and in one (
language: eng
source: Alma/SFX Local Collection
identifier: ISSN: 0140-6736
fulltext: fulltext
issn:
  • 0140-6736
  • 0099-5355
  • 1474-547X
url: Link


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titleOnce-daily atazanavir/ritonavir versus twice-daily lopinavir/ritonavir, each in combination with tenofovir and emtricitabine, for management of antiretroviral-naive HIV-1-infected patients: 48 week efficacy and safety results of the CASTLE study
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creatorMolina, Jean-Michel, Prof ; Andrade-Villanueva, Jaime, MD ; Echevarria, Juan, MD ; Chetchotisakd, Ploenchan, Prof ; Corral, Jorge, MD ; David, Neal, FCFP [SA] ; Moyle, Graeme, MD ; Mancini, Marco, BS ; Percival, Lisa, MS ; Yang, Rong, PhD ; Thiry, Alexandra, PhD ; McGrath, Donnie, MD
creatorcontribMolina, Jean-Michel, Prof ; Andrade-Villanueva, Jaime, MD ; Echevarria, Juan, MD ; Chetchotisakd, Ploenchan, Prof ; Corral, Jorge, MD ; David, Neal, FCFP [SA] ; Moyle, Graeme, MD ; Mancini, Marco, BS ; Percival, Lisa, MS ; Yang, Rong, PhD ; Thiry, Alexandra, PhD ; McGrath, Donnie, MD ; for the CASTLE Study Team ; CASTLE Study Team
descriptionSummary Background Atazanavir/ritonavir is as effective as lopinavir/ritonavir, with a more favourable lipid profile and less gastrointestinal toxicity, in treatment-experienced HIV-1-infected patients. We compared these two combinations directly in treatment-naive patients. Methods In this open-label, international non-inferiority study, 883 antiretroviral-naive, HIV-1-infected patients were randomly assigned to receive atazanavir/ritonavir 300/100 mg once daily (n=440) or lopinavir/ritonavir 400/100 mg twice daily (n=443), in combination with fixed-dose tenofovir/emtricitabine 300/200 mg once daily. Randomisation was done with a computer-generated centralised randomisation schedule and was stratified by baseline levels of HIV RNA (viral load) and geographic region. The primary endpoint was the proportion of patients with viral load less than 50 copies per mL at week 48. The main efficacy analysis was done by intention to treat. This trial is registered with ClinicalTrials.gov , number NCT00272779. Findings At week 48, 343 (78%) of 440 patients receiving atazanavir/ritonavir and 338 (76%) of 443 patients receiving lopinavir/ritonavir had achieved a viral load of less than 50 copies per mL (difference 1·7%, 95% CI −3·8 to 7·1). Mean increases from baseline in CD4 cell count were similar (203 cells per μL in the atazanavir/ritonavir group vs 219 cells per μL in the lopinavir/ritonavir group). 25 (6%) patients in the atazanavir/ritonavir group and 26 (6%) in the lopinavir/ritonavir group were virological failures by week 48. Only two patients, both in the atazanavir/ritonavir group, had non-polymorphic protease inhibitor resistance mutations emerge on treatment, which conferred phenotypic resistance to atazanavir in one patient. Serious adverse events were noted in 51 (12%) of 441 patients in the atazanavir/ritonavir group and in 42 (10%) of 437 patients in the lopinavir/ritonavir group. Fewer patients in the atazanavir/ritonavir group than in the lopinavir/ritonavir group experienced grade 2–4 treatment-related diarrhoea (10 [2%] vs 50 [11%]) and nausea (17 [4%] vs 33 [8%]). Grade 2–4 jaundice was seen in 16 (4%) of 441 patients in the atazanavir/ritonavir group versus none of 437 patients in the lopinavir/ritonavir group; grade 3–4 increases in total bilirubin were seen in 146 (34%) of 435 patients on atazanavir/ritonavir and in one (<1%) of 431 patients on lopinavir/ritonavir. Interpretation In treatment-naive patients, atazanavir/ritonavir once-daily demonstrated similar antiviral efficacy to lopinavir/ritonavir twice-daily, with less gastrointestinal toxicity but with a higher rate of hyperbilirubinaemia. Funding Bristol-Myers Squibb.
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subjectAdult ; Aged ; Antiretroviral drugs ; Atazanavir Sulfate ; Clinical medicine ; Drug Administration Schedule ; Drug therapy ; Drug Therapy, Combination ; Female ; Heart attacks ; HIV ; HIV Infections - drug therapy ; HIV Protease Inhibitors - administration & dosage ; HIV Protease Inhibitors - adverse effects ; HIV Protease Inhibitors - therapeutic use ; HIV-1 ; Human immunodeficiency virus ; Humans ; Internal Medicine ; Lopinavir ; Male ; Middle Aged ; Mortality ; Oligopeptides - administration & dosage ; Oligopeptides - adverse effects ; Oligopeptides - therapeutic use ; Patients ; Pyridines - administration & dosage ; Pyridines - adverse effects ; Pyridines - therapeutic use ; Pyrimidinones - administration & dosage ; Pyrimidinones - adverse effects ; Pyrimidinones - therapeutic use ; Ritonavir - administration & dosage ; Ritonavir - adverse effects ; Ritonavir - therapeutic use ; Sample size ; Studies ; Viral Load
ispartofThe Lancet (British edition), 2008, Vol.372 (9639), p.646-655
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1Andrade-Villanueva, Jaime, MD
2Echevarria, Juan, MD
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5David, Neal, FCFP [SA]
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7Mancini, Marco, BS
8Percival, Lisa, MS
9Yang, Rong, PhD
10Thiry, Alexandra, PhD
11McGrath, Donnie, MD
12for the CASTLE Study Team
13CASTLE Study Team
title
0Once-daily atazanavir/ritonavir versus twice-daily lopinavir/ritonavir, each in combination with tenofovir and emtricitabine, for management of antiretroviral-naive HIV-1-infected patients: 48 week efficacy and safety results of the CASTLE study
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descriptionSummary Background Atazanavir/ritonavir is as effective as lopinavir/ritonavir, with a more favourable lipid profile and less gastrointestinal toxicity, in treatment-experienced HIV-1-infected patients. We compared these two combinations directly in treatment-naive patients. Methods In this open-label, international non-inferiority study, 883 antiretroviral-naive, HIV-1-infected patients were randomly assigned to receive atazanavir/ritonavir 300/100 mg once daily (n=440) or lopinavir/ritonavir 400/100 mg twice daily (n=443), in combination with fixed-dose tenofovir/emtricitabine 300/200 mg once daily. Randomisation was done with a computer-generated centralised randomisation schedule and was stratified by baseline levels of HIV RNA (viral load) and geographic region. The primary endpoint was the proportion of patients with viral load less than 50 copies per mL at week 48. The main efficacy analysis was done by intention to treat. This trial is registered with ClinicalTrials.gov , number NCT00272779. Findings At week 48, 343 (78%) of 440 patients receiving atazanavir/ritonavir and 338 (76%) of 443 patients receiving lopinavir/ritonavir had achieved a viral load of less than 50 copies per mL (difference 1·7%, 95% CI −3·8 to 7·1). Mean increases from baseline in CD4 cell count were similar (203 cells per μL in the atazanavir/ritonavir group vs 219 cells per μL in the lopinavir/ritonavir group). 25 (6%) patients in the atazanavir/ritonavir group and 26 (6%) in the lopinavir/ritonavir group were virological failures by week 48. Only two patients, both in the atazanavir/ritonavir group, had non-polymorphic protease inhibitor resistance mutations emerge on treatment, which conferred phenotypic resistance to atazanavir in one patient. Serious adverse events were noted in 51 (12%) of 441 patients in the atazanavir/ritonavir group and in 42 (10%) of 437 patients in the lopinavir/ritonavir group. Fewer patients in the atazanavir/ritonavir group than in the lopinavir/ritonavir group experienced grade 2–4 treatment-related diarrhoea (10 [2%] vs 50 [11%]) and nausea (17 [4%] vs 33 [8%]). Grade 2–4 jaundice was seen in 16 (4%) of 441 patients in the atazanavir/ritonavir group versus none of 437 patients in the lopinavir/ritonavir group; grade 3–4 increases in total bilirubin were seen in 146 (34%) of 435 patients on atazanavir/ritonavir and in one (<1%) of 431 patients on lopinavir/ritonavir. Interpretation In treatment-naive patients, atazanavir/ritonavir once-daily demonstrated similar antiviral efficacy to lopinavir/ritonavir twice-daily, with less gastrointestinal toxicity but with a higher rate of hyperbilirubinaemia. Funding Bristol-Myers Squibb.
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titleOnce-daily atazanavir/ritonavir versus twice-daily lopinavir/ritonavir, each in combination with tenofovir and emtricitabine, for management of antiretroviral-naive HIV-1-infected patients: 48 week efficacy and safety results of the CASTLE study
authorMolina, Jean-Michel, Prof ; Andrade-Villanueva, Jaime, MD ; Echevarria, Juan, MD ; Chetchotisakd, Ploenchan, Prof ; Corral, Jorge, MD ; David, Neal, FCFP [SA] ; Moyle, Graeme, MD ; Mancini, Marco, BS ; Percival, Lisa, MS ; Yang, Rong, PhD ; Thiry, Alexandra, PhD ; McGrath, Donnie, MD
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eissn1474-547X
codenLANCAO
abstractSummary Background Atazanavir/ritonavir is as effective as lopinavir/ritonavir, with a more favourable lipid profile and less gastrointestinal toxicity, in treatment-experienced HIV-1-infected patients. We compared these two combinations directly in treatment-naive patients. Methods In this open-label, international non-inferiority study, 883 antiretroviral-naive, HIV-1-infected patients were randomly assigned to receive atazanavir/ritonavir 300/100 mg once daily (n=440) or lopinavir/ritonavir 400/100 mg twice daily (n=443), in combination with fixed-dose tenofovir/emtricitabine 300/200 mg once daily. Randomisation was done with a computer-generated centralised randomisation schedule and was stratified by baseline levels of HIV RNA (viral load) and geographic region. The primary endpoint was the proportion of patients with viral load less than 50 copies per mL at week 48. The main efficacy analysis was done by intention to treat. This trial is registered with ClinicalTrials.gov , number NCT00272779. Findings At week 48, 343 (78%) of 440 patients receiving atazanavir/ritonavir and 338 (76%) of 443 patients receiving lopinavir/ritonavir had achieved a viral load of less than 50 copies per mL (difference 1·7%, 95% CI −3·8 to 7·1). Mean increases from baseline in CD4 cell count were similar (203 cells per μL in the atazanavir/ritonavir group vs 219 cells per μL in the lopinavir/ritonavir group). 25 (6%) patients in the atazanavir/ritonavir group and 26 (6%) in the lopinavir/ritonavir group were virological failures by week 48. Only two patients, both in the atazanavir/ritonavir group, had non-polymorphic protease inhibitor resistance mutations emerge on treatment, which conferred phenotypic resistance to atazanavir in one patient. Serious adverse events were noted in 51 (12%) of 441 patients in the atazanavir/ritonavir group and in 42 (10%) of 437 patients in the lopinavir/ritonavir group. Fewer patients in the atazanavir/ritonavir group than in the lopinavir/ritonavir group experienced grade 2–4 treatment-related diarrhoea (10 [2%] vs 50 [11%]) and nausea (17 [4%] vs 33 [8%]). Grade 2–4 jaundice was seen in 16 (4%) of 441 patients in the atazanavir/ritonavir group versus none of 437 patients in the lopinavir/ritonavir group; grade 3–4 increases in total bilirubin were seen in 146 (34%) of 435 patients on atazanavir/ritonavir and in one (<1%) of 431 patients on lopinavir/ritonavir. Interpretation In treatment-naive patients, atazanavir/ritonavir once-daily demonstrated similar antiviral efficacy to lopinavir/ritonavir twice-daily, with less gastrointestinal toxicity but with a higher rate of hyperbilirubinaemia. Funding Bristol-Myers Squibb.
copEngland
pubElsevier Ltd
pmid18722869
doi10.1016/S0140-6736(08)61081-8