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

J Acquir Immune Defic Syndr. 2010 Mar;53(3):323-32. doi: 10.1097/QAI.0b013e3181c990bf.

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.

Publication types

  • Comparative Study
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • 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
  • RNA, Viral / blood
  • Ritonavir / administration & dosage*
  • Ritonavir / adverse effects
  • Tenofovir
  • Treatment Outcome
  • Viral Load
  • Young Adult

Substances

  • Anti-HIV Agents
  • Lipids
  • Oligopeptides
  • Organophosphonates
  • Pyridines
  • Pyrimidinones
  • RNA, Viral
  • Deoxycytidine
  • Lopinavir
  • Atazanavir Sulfate
  • Tenofovir
  • Emtricitabine
  • Adenine
  • Ritonavir