title: Early lipid changes with atazanavir/ritonavir or darunavir/ritonavir.
abstract: OBJECTIVE
  Ritonavir-boosted atazanavir and darunavir are protease inhibitors that are recommended for initial treatment of HIV infection because each has shown better lipid effects and overall tolerability than ritonavir-boosted lopinavir. The extent to which lipid effects and overall tolerability differ between treatments with atazanavir and darunavir and whether atazanavir-induced hyperbilirubinaemia may result in more favourable metabolic effects are issues that remain to be resolved.
  
  
  METHODS
  A 96-week randomized clinical trial was carried out. The primary endpoint was change in total cholesterol at 24 weeks. Secondary endpoints were changes in lipids other than total cholesterol, insulin sensitivity, total bilirubin, estimated glomerular filtration rate, and CD4 and CD8 cell counts, and the proportion of patients with plasma HIV RNA < 50 HIV-1 RNA copies/mL and study drug discontinuation because of adverse effects at 24 weeks. Analyses were intent-to-treat.
  
  
  RESULTS
  One hundred and seventy-eight patients received once-daily treatment with either atazanavir/ritonavir (n = 90) or darunavir/ritonavir (n = 88) plus tenofovir/emtricitabine. At 24 weeks, mean total cholesterol had increased by 7.26 and 11.47 mg/dL in the atazanavir/ritonavir and darunavir/ritonavir arms, respectively [estimated difference -4.21 mg/dL; 95% confidence interval (CI) -12.11 to +3.69 mg/dL; P = 0.75]. However, the ratio of total to high-density lipoprotein (HDL) cholesterol tended to show a greater decrease with atazanavir/ritonavir compared with darunavir/ritonavir (estimated difference -1.02; 95% CI -2.35 to +0.13; P = 0.07). Total bilirubin significantly increased with atazanavir/ritonavir (estimated difference +1.87 mg/dL; 95% CI +1.58 to +2.16 mg/dL; P < 0.01), but bilirubin changes were not associated with lipid changes. Secondary endpoints other than total bilirubin were not significantly different between arms.
  
  
  CONCLUSIONS
  Atazanavir/ritonavir and darunavir/ritonavir plus tenofovir/emtricitabine did not show significant differences in total cholesterol change or overall tolerability at 24 weeks. However, there was a trend towards a lower total to HDL cholesterol ratio with atazanavir/ritonavir and this effect was unrelated to bilirubin.
authors.affiliation: Hospital Clínic-IDIBAPS, Universitat de Barcelona, Barcelona, Spain.
authors.forename: E
authors.initials: E
authors.lastname: Martinez
authors.forename: A
authors.initials: A
authors.lastname: Gonzalez-Cordon
authors.forename: E
authors.initials: E
authors.lastname: Ferrer
authors.forename: P
authors.initials: P
authors.lastname: Domingo
authors.forename: E
authors.initials: E
authors.lastname: Negredo
authors.forename: F
authors.initials: F
authors.lastname: Gutierrez
authors.forename: J
authors.initials: J
authors.lastname: Portilla
authors.forename: A
authors.initials: A
authors.lastname: Curran
authors.forename: D
authors.initials: D
authors.lastname: Podzamczer
authors.forename: J
authors.initials: J
authors.lastname: Murillas
authors.forename: J I
authors.initials: JI
authors.lastname: Bernardino
authors.forename: I
authors.initials: I
authors.lastname: Santos
authors.forename: J A
authors.initials: JA
authors.lastname: Carton
authors.forename: J
authors.initials: J
authors.lastname: Peraire
authors.forename: J
authors.initials: J
authors.lastname: Pich
authors.forename: I
authors.initials: I
authors.lastname: Perez
authors.forename: J M
authors.initials: JM
authors.lastname: Gatell
mesh_terms: D000328:Adult; D000069446:Atazanavir Sulfate; D001663:Bilirubin; D018791:CD4 Lymphocyte Count; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology; D000069454:Darunavir; D004359:Drug Therapy, Combination / Q000379:methods; D005260:Female; D005919:Glomerular Filtration Rate; D015658:HIV Infections / Q000097:blood / Q000188:drug therapy* / Q000503:physiopathology; D017320:HIV Protease Inhibitors / Q000009:adverse effects / Q000627:therapeutic use*; D006801:Humans; D006932:Hyperbilirubinemia / Q000139:chemically induced; D008055:Lipids / Q000097:blood*; D008297:Male; D008875:Middle Aged; D009842:Oligopeptides / Q000008:administration & dosage; D011446:Prospective Studies; D011725:Pyridines / Q000008:administration & dosage; D012367:RNA, Viral / Q000032:analysis; D019438:Ritonavir / Q000008:administration & dosage; D013030:Spain; D013449:Sulfonamides / Q000008:administration & dosage
chemical_list: D017320:HIV Protease Inhibitors; D008055:Lipids; D009842:Oligopeptides; D011725:Pyridines; D012367:RNA, Viral; D013449:Sulfonamides; D000069446:Atazanavir Sulfate; D019438:Ritonavir; D001663:Bilirubin; D000069454:Darunavir
keywords: atazanavir; darunavir; lipids