title: 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.
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.
authors.affiliation: Department of Infectious Diseases, Hopital Saint-Louis 1, Av. C. Vellefaux, 75475 Paris, Cedex 10, France. jean-michel.molina@sls.ap-hop-paris.fr
authors.forename: Jean-Michel
authors.initials: JM
authors.lastname: Molina
authors.forename: Jaime
authors.initials: J
authors.lastname: Andrade-Villanueva
authors.forename: Juan
authors.initials: J
authors.lastname: Echevarria
authors.forename: Ploenchan
authors.initials: P
authors.lastname: Chetchotisakd
authors.forename: Jorge
authors.initials: J
authors.lastname: Corral
authors.forename: Neal
authors.initials: N
authors.lastname: David
authors.forename: Graeme
authors.initials: G
authors.lastname: Moyle
authors.forename: Marco
authors.initials: M
authors.lastname: Mancini
authors.forename: Lisa
authors.initials: L
authors.lastname: Percival
authors.forename: Rong
authors.initials: R
authors.lastname: Yang
authors.forename: Victoria
authors.initials: V
authors.lastname: Wirtz
authors.forename: Max
authors.initials: M
authors.lastname: Lataillade
authors.forename: Judith
authors.initials: J
authors.lastname: Absalon
authors.forename: Donnie
authors.initials: D
authors.lastname: McGrath
mesh_terms: D000225:Adenine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives*; D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D019380:Anti-HIV Agents / Q000008:administration & dosage* / Q000009:adverse effects; D023241:Antiretroviral Therapy, Highly Active / Q000379:methods; D000069446:Atazanavir Sulfate; D003841:Deoxycytidine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives*; D000068679:Emtricitabine; D005260:Female; D015658:HIV Infections / Q000188:drug therapy* / Q000821:virology; D015497:HIV-1 / Q000302:isolation & purification; D006801:Humans; D008055:Lipids / Q000097:blood; D061466:Lopinavir; D008297:Male; D008875:Middle Aged; D009842:Oligopeptides / Q000008:administration & dosage* / Q000009:adverse effects; D063065:Organophosphonates / Q000008:administration & dosage* / Q000009:adverse effects; D011725:Pyridines / Q000008:administration & dosage* / Q000009:adverse effects; D011744:Pyrimidinones / Q000008:administration & dosage* / Q000009:adverse effects; D012367:RNA, Viral / Q000097:blood; D019438:Ritonavir / Q000008:administration & dosage* / Q000009:adverse effects; D000068698:Tenofovir; D016896:Treatment Outcome; D019562:Viral Load; D055815:Young Adult
chemical_list: D019380:Anti-HIV Agents; D008055:Lipids; D009842:Oligopeptides; D063065:Organophosphonates; D011725:Pyridines; D011744:Pyrimidinones; D012367:RNA, Viral; D003841:Deoxycytidine; D061466:Lopinavir; D000069446:Atazanavir Sulfate; D000068698:Tenofovir; D000068679:Emtricitabine; D000225:Adenine; D019438:Ritonavir