Literature DB >> 20032785

Once-daily atazanavir/ritonavir compared with twice-daily lopinavir/ritonavir, each in combination with tenofovir and emtricitabine, for management of antiretroviral-naive HIV-1-infected patients: 96-week efficacy and safety results of the CASTLE study.

Jean-Michel Molina1, Jaime Andrade-Villanueva, Juan Echevarria, Ploenchan Chetchotisakd, Jorge Corral, Neal David, Graeme Moyle, Marco Mancini, Lisa Percival, Rong Yang, Victoria Wirtz, Max Lataillade, Judith Absalon, Donnie McGrath.   

Abstract

BACKGROUND: Once-daily atazanavir/ritonavir demonstrated similar antiviral efficacy to twice-daily lopinavir/ritonavir over 48 weeks, with less gastrointestinal disturbance and a better lipid profile, in treatment-naive patients.
METHODS: International, multicenter, open-label, 96-week noninferiority randomized trial of atazanavir/ritonavir 300/100 mg once daily vs lopinavir/ritonavir 400/100 mg twice daily, each in combination with fixed-dose tenofovir/emtricitabine 300/200 mg once daily, in antiretroviral-naive, HIV-1-infected patients. The primary end point was the proportion of patients with HIV RNA <50 copies/mL at 48 weeks. Results through 96 weeks are reported.
RESULTS: Of 883 patients enrolled, 440 were randomized to atazanavir/ritonavir and 443 to lopinavir/ritonavir. At week 96, more patients receiving atazanavir/ritonavir achieved HIV RNA <50 copies/mL (74% vs 68%, P < 0.05) in the intent-to-treat analysis. On both regimens, 7% of subjects were virologic failures by 96 weeks. Bilirubin-associated disorders were greater in patients taking atazanavir/ritonavir. Treatment-related gastrointestinal adverse events were greater in patients taking lopinavir/ritonavir. Mean changes from baseline in fasting total cholesterol, non-high-density lipoprotein cholesterol, and triglycerides at week 96 were significantly higher with lopinavir/ritonavir (P < 0.0001).
CONCLUSIONS: Noninferiority of atazanavir/ritonavir to lopinavir/ritonavir was confirmed at 96 weeks. Atazanavir/ritonavir had a better lipid profile and fewer gastrointestinal adverse events than lopinavir/ritonavir.

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Year:  2010        PMID: 20032785     DOI: 10.1097/QAI.0b013e3181c990bf

Source DB:  PubMed          Journal:  J Acquir Immune Defic Syndr        ISSN: 1525-4135            Impact factor:   3.731


  79 in total

1.  Clinical significance of hyperbilirubinemia among HIV-1-infected patients treated with atazanavir/ritonavir through 96 weeks in the CASTLE study.

Authors:  Cheryl McDonald; Jonathan Uy; Wenhua Hu; Victoria Wirtz; Salome Juethner; David Butcher; Donnie McGrath; Awny Farajallah; Graeme Moyle
Journal:  AIDS Patient Care STDS       Date:  2012-03-09       Impact factor: 5.078

2.  Symptomatic hyperbilirubinemia secondary to dapsone-induced hemolysis and atazanavir therapy.

Authors:  Jeff East; Lucas Scott Blanton
Journal:  Antimicrob Agents Chemother       Date:  2011-11-28       Impact factor: 5.191

3.  In vitro antiviral characteristics of HIV-1 attachment inhibitor BMS-626529, the active component of the prodrug BMS-663068.

Authors:  Beata Nowicka-Sans; Yi-Fei Gong; Brian McAuliffe; Ira Dicker; Hsu-Tso Ho; Nannan Zhou; Betsy Eggers; Pin-Fang Lin; Neelanjana Ray; Megan Wind-Rotolo; Li Zhu; Antara Majumdar; David Stock; Max Lataillade; George J Hanna; John D Matiskella; Yasutsugu Ueda; Tao Wang; John F Kadow; Nicholas A Meanwell; Mark Krystal
Journal:  Antimicrob Agents Chemother       Date:  2012-04-30       Impact factor: 5.191

Review 4.  Novel clinical trial designs for the development of new antiretroviral agents.

Authors:  Nina Mani; Jeffrey Murray; Roy M Gulick; Filip Josephson; Veronica Miller; Peter Miele; Jur Strobos; Kimberly Struble
Journal:  AIDS       Date:  2012-05-15       Impact factor: 4.177

5.  Pharmacokinetic interactions between BMS-626529, the active moiety of the HIV-1 attachment inhibitor prodrug BMS-663068, and ritonavir or ritonavir-boosted atazanavir in healthy subjects.

Authors:  Li Zhu; Matthew Hruska; Carey Hwang; Vaishali Shah; Michael Furlong; George J Hanna; Richard Bertz; Ishani Savant Landry
Journal:  Antimicrob Agents Chemother       Date:  2015-04-13       Impact factor: 5.191

6.  Antiretroviral treatment 2010: progress and controversies.

Authors:  Roy M Gulick
Journal:  J Acquir Immune Defic Syndr       Date:  2010-12       Impact factor: 3.731

7.  Protease Inhibitors for Patients With HIV-1 Infection: A Comparative Overview.

Authors:  Peter J Hughes; Erika Cretton-Scott; Ami Teague; Terri M Wensel
Journal:  P T       Date:  2011-06

8.  HIV-1 suppression and durable control by combining single broadly neutralizing antibodies and antiretroviral drugs in humanized mice.

Authors:  Joshua A Horwitz; Ariel Halper-Stromberg; Hugo Mouquet; Alexander D Gitlin; Anna Tretiakova; Thomas R Eisenreich; Marine Malbec; Sophia Gravemann; Eva Billerbeck; Marcus Dorner; Hildegard Büning; Olivier Schwartz; Elena Knops; Rolf Kaiser; Michael S Seaman; James M Wilson; Charles M Rice; Alexander Ploss; Pamela J Bjorkman; Florian Klein; Michel C Nussenzweig
Journal:  Proc Natl Acad Sci U S A       Date:  2013-09-16       Impact factor: 11.205

9.  Comparison of body composition changes between atazanavir/ritonavir and lopinavir/ritonavir each in combination with tenofovir/emtricitabine in antiretroviral-naïve patients with HIV-1 infection.

Authors:  Graeme J Moyle; Hélène Hardy; Awny Farajallah; Michelle DeGrosky; Donnie McGrath
Journal:  Clin Drug Investig       Date:  2014-04       Impact factor: 2.859

10.  Population pharmacokinetic modelling of the changes in atazanavir plasma clearance caused by ritonavir plasma concentrations in HIV-1 infected patients.

Authors:  José Moltó; Javier A Estévez; Cristina Miranda; Samandhy Cedeño; Bonaventura Clotet; Marta Valle
Journal:  Br J Clin Pharmacol       Date:  2016-09-13       Impact factor: 4.335

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