title: Therapy with atazanavir plus saquinavir in patients failing highly active antiretroviral therapy: a randomized comparative pilot trial.
abstract: OBJECTIVE
  To assess the safety, efficacy of atazanavir (400 and 600 mg)/saquinavir (1200 mg) once daily versus ritonavir/saquinavir (400 mg/400 mg) twice daily with two nucleoside reverse transcriptase inhibitors (NRTIs) in highly active antiretroviral therapy failure.
  
  
  METHODS
  Randomized, multinational, 48-week, pilot trial with antiretroviral-experienced patients having at least 1000 HIV-1 RNA copies/ml, 100 x 106 CD4 cells/l (75 x 106 cells/l without AIDS diagnosis) and virological response to a prior regimen. Efficacy was evaluated by HIV-1 RNA and CD4 cell changes from baseline to 48 weeks.
  
  
  RESULTS
  Comparable efficacy across groups at 48 weeks: mean HIV-1 RNA decreases, 1.44, 1.19 and 1.66 log(10) copies/ml (P = NS) and comparable virological response (> 1.0 log(10) decrease HIV-1 RNA or HIV-1 RNA < 400 copies/ml) was achieved in 41, 29 and 35% (P = NS); and mean CD4 cell increases, 109, 55 and 149 x 106 cells/l in atazanavir 400-mg, atazanavir 600-mg and ritonavir groups, respectively. There were fewer adverse event discontinuations in the atazanavir groups (9%, 11%) versus the ritonavir group (30%) and atazanavir lacked adverse effects on lipids. In the atazanavir 400-mg, atazanavir 600-mg and ritonavir groups the mean changes from baseline at 48 weeks in fasting low-density lipoprotein (LDL) cholesterol concentrations were -0.6, -6.7 and 23.2%, respectively and in fasting triglyceride concentrations they were -4.8, -27.1 and 93.0%, respectively (P < 0.05, LDL cholesterol; P < 0.001, fasting triglyceride; atazanavir/saquinavir versus ritonavir/saquinavir).
  
  
  CONCLUSIONS
  In antiretroviral-experienced patients, once-daily atazanavir/saquinavir was safe and well tolerated, showing comparable efficacy to twice-daily ritonavir/saquinavir, both with two NRTIs. Small lipid changes from baseline with atazanavir/saquinavir were not clinically significant in comparison with the prompt, marked and sustained changes of a magnitude suggesting clinical relevance achieved in the ritonavir/saquinavir group.
authors.affiliation: Vanderbilt University School of Medicine, Nashville, Tennessee 37212, USA. david.w.haas@vanderbilt.edu
authors.forename: David W
authors.initials: DW
authors.lastname: Haas
authors.forename: Carlos
authors.initials: C
authors.lastname: Zala
authors.forename: Shannon
authors.initials: S
authors.lastname: Schrader
authors.forename: Peter
authors.initials: P
authors.lastname: Piliero
authors.forename: Hans
authors.initials: H
authors.lastname: Jaeger
authors.forename: Danilo
authors.initials: D
authors.lastname: Nunes
authors.forename: Alexandra
authors.initials: A
authors.lastname: Thiry
authors.forename: Steven
authors.initials: S
authors.lastname: Schnittman
authors.forename: Michael
authors.initials: M
authors.lastname: Sension
mesh_terms: D000328:Adult; D023241:Antiretroviral Therapy, Highly Active; D000069446:Atazanavir Sulfate; D018791:CD4 Lymphocyte Count; D004334:Drug Administration Schedule; D004359:Drug Therapy, Combination; D005260:Female; D015658:HIV Infections / Q000097:blood / Q000188:drug therapy* / Q000276:immunology; D015497:HIV-1 / Q000235:genetics; D006801:Humans; D008055:Lipids / Q000097:blood; D008297:Male; D009842:Oligopeptides / Q000627:therapeutic use*; D010865:Pilot Projects; D011480:Protease Inhibitors / Q000627:therapeutic use*; D011725:Pyridines / Q000627:therapeutic use*; D012367:RNA, Viral / Q000032:analysis; D019438:Ritonavir / Q000627:therapeutic use; D016879:Salvage Therapy; D019258:Saquinavir / Q000627:therapeutic use*; D017211:Treatment Failure
chemical_list: D008055:Lipids; D009842:Oligopeptides; D011480:Protease Inhibitors; D011725:Pyridines; D012367:RNA, Viral; D000069446:Atazanavir Sulfate; D019258:Saquinavir; D019438:Ritonavir