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

• Published in: Journal of acquired immune deficiency syndromes (1999) Vol. 53; no. 3; p. 323
• Main Authors: Molina, Jean-Michel, Andrade-Villanueva, Jaime, Echevarria, Juan, Chetchotisakd, Ploenchan, Corral, Jorge, David, Neal, Moyle, Graeme, Mancini, Marco, Percival, Lisa, Yang, Rong, Wirtz, Victoria, Lataillade, Max, Absalon, Judith, McGrath, Donnie
• Format: Journal Article
• Language: English
• Published: United States 01.03.2010
• Subjects: Adenine - administration & dosage; Adenine - adverse effects; Adenine - analogs & derivatives; Adolescent; Adult; Aged; Aged, 80 and over; Anti-HIV Agents - administration & dosage; Anti-HIV Agents - adverse effects; Antiretroviral Therapy, Highly Active - methods; Atazanavir Sulfate; Deoxycytidine - administration & dosage; Deoxycytidine - adverse effects; Deoxycytidine - analogs & derivatives; Emtricitabine; Female; HIV Infections - drug therapy; HIV Infections - virology; HIV-1 - isolation & purification; Humans; Lipids - blood; Lopinavir; Male; Middle Aged; Oligopeptides - administration & dosage; Oligopeptides - adverse effects; Organophosphonates - administration & dosage; Organophosphonates - adverse effects; Pyridines - administration & dosage; Pyridines - adverse effects; Pyrimidinones - administration & dosage; Pyrimidinones - adverse effects; Ritonavir - administration & dosage; Ritonavir - adverse effects; RNA, Viral - blood; Tenofovir; Treatment Outcome; Viral Load; Young Adult
• ISSN: 1944-7884
• DOI: 10.1097/QAI.0b013e3181c990bf

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. 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. 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). 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.