title: Metabolic effects of darunavir/ritonavir versus atazanavir/ritonavir in treatment-naive, HIV type 1-infected subjects over 48 weeks.
abstract: We assessed metabolic changes for darunavir/ritonavir (DRV/r) once daily (qd) versus atazanavir/ritonavir (ATV/r) qd with fixed-dose tenofovir/emtricitabine. This was a phase 4, multicenter, open-label, randomized exploratory study. Treatment-naive, HIV-1-infected adults received DRV/r 800/100 mg qd or ATV/r 300/100 mg qd, both with emtricitabine/tenofovir 200/300 mg qd. Primary end point: change in triglyceride levels from baseline to week 12. Secondary end points: week 12 and week 48 changes in lipid parameters, insulin sensitivity, inflammatory/coagulation/bacterial translocation biomarkers, viral load, CD4(+) cell count, and week 48 changes in adipose tissue distribution and subjects' perceptions of body changes. In the DRV/r arm, 32/34 and 29/34 subjects completed weeks 12 and 48, respectively; in the ATV/r arm, 30/31 and 25/31 subjects completed weeks 12 and 48, respectively. Small changes in lipid parameters from baseline to weeks 12 and 48 were observed in both arms. Differences were noted between arms in mean changes in total cholesterol (DRV/r, 20.3 mg/dl; ATV/r, 4.6 mg/dl) and apolipoprotein A1 (DRV/r, 10.7 mg/dl; ATV/r, -0.7 mg/dl) at week 12. At week 48, no clinically relevant differences between arms were noted for changes in any lipid parameter, fasting glucose, or insulin sensitivity. Biomarkers generally decreased and efficacy parameters improved in both arms over 48 weeks. Changes in adipose tissue were small and comparable between arms. Subjects' perceptions of body changes generally improved in both study arms. This first pilot comparison in HIV-1-infected subjects suggests that DRV/r has a metabolic profile similar to ATV/r over 48 weeks of treatment. Further randomized studies are warranted.
authors.affiliation: Bellevue Hospital Center at New York University School of Medicine, New York, USA. judith.aberg@med.nyu.edu
authors.forename: Judith A
authors.initials: JA
authors.lastname: Aberg
authors.forename: Pablo
authors.initials: P
authors.lastname: Tebas
authors.forename: Edgar Turner
authors.initials: ET
authors.lastname: Overton
authors.forename: Samir K
authors.initials: SK
authors.lastname: Gupta
authors.forename: Paul E
authors.initials: PE
authors.lastname: Sax
authors.forename: Alan
authors.initials: A
authors.lastname: Landay
authors.forename: Ron
authors.initials: R
authors.lastname: Falcon
authors.forename: Robert
authors.initials: R
authors.lastname: Ryan
authors.forename: Guy
authors.initials: G
authors.lastname: De La Rosa
mesh_terms: D000163:Acquired Immunodeficiency Syndrome / Q000188:drug therapy / Q000378:metabolism*; D000328:Adult; D000368:Aged; D000069446:Atazanavir Sulfate; D015415:Biomarkers / Q000097:blood / Q000378:metabolism; D018791:CD4 Lymphocyte Count; D000069454:Darunavir; D018450:Disease Progression; D004334:Drug Administration Schedule; D024882:Drug Resistance, Viral; D004359:Drug Therapy, Combination; D005260:Female; D005919:Glomerular Filtration Rate; D017320:HIV Protease Inhibitors / Q000008:administration & dosage / Q000494:pharmacology*; D015497:HIV-1 / Q000187:drug effects / Q000378:metabolism*; D006801:Humans; D007333:Insulin Resistance; D008055:Lipids / Q000097:blood*; D008297:Male; D008875:Middle Aged; D009842:Oligopeptides / Q000008:administration & dosage / Q000494:pharmacology*; D010865:Pilot Projects; D011725:Pyridines / Q000008:administration & dosage / Q000494:pharmacology*; D012367:RNA, Viral / Q000097:blood; D019438:Ritonavir / Q000008:administration & dosage / Q000494:pharmacology*; D013449:Sulfonamides / Q000008:administration & dosage / Q000494:pharmacology*; D013997:Time Factors; D016896:Treatment Outcome; D019562:Viral Load; D055815:Young Adult
chemical_list: D015415:Biomarkers; D017320:HIV Protease Inhibitors; D008055:Lipids; D009842:Oligopeptides; D011725:Pyridines; D012367:RNA, Viral; D013449:Sulfonamides; D000069446:Atazanavir Sulfate; D019438:Ritonavir; D000069454:Darunavir