title: Randomized comparison of metabolic and renal effects of saquinavir/r or atazanavir/r plus tenofovir/emtricitabine in treatment-naïve HIV-1-infected patients.
abstract: OBJECTIVE
  The aim of the study was to compare the effects on lipids, body composition and renal function of once-daily ritonavir-boosted saquinavir (SQV/r) or atazanavir (ATV/r) in combination with tenofovir/emtricitabine (TDF/FTC) over 48 weeks.
  
  
  METHODS
  An investigator-initiated, randomized, open-label, multinational trial comparing SQV/r 2000/100 mg and ATV/r 300/100 mg once daily, both in combination with TDF/FTC, in 123 treatment-naïve HIV-1-infected adults was carried out. The primary endpoint was to demonstrate noninferiority of SQV/r compared with ATV/r with respect to the change in fasting cholesterol after 24 weeks. Secondary outcome measures were changes in metabolic abnormalities, body composition, renal function, and virological and immunological efficacy over 48 weeks. Patients who had used at least one dose of trial drug were included in the analysis.
  
  
  RESULTS
  Data for 118 patients were analysed (57 patients on SQV/r and 61 on ATV/r). At week 24, changes in lipids were modest, without increases in triglycerides, including a significant rise in high-density lipoprotein (HDL) cholesterol and a nonsignificant decrease in the total:HDL cholesterol ratio in both arms with no significant difference between arms. Lipid changes at week 48 were similar to the changes observed up to week 24, with no significant change in the homeostasis model assessment (HOMA) index. Adipose tissue increased regardless of the regimen, particularly in the peripheral compartment and to a lesser extent in the central abdominal compartment, with an increase in adipose tissue reaching statistical significance in the ATV/r arm. A slight decline in the estimated glomerular filtration rate (eGFR) was observed in both arms during the first 24 weeks, with no progression thereafter. The immunological and virological responses were similar over the 48 weeks.
  
  
  CONCLUSIONS
  Combined with TDF/FTC, both SQV/r 2000/100 mg and ATV/r 300/100 mg had comparable modest effects on lipids, had little effect on glucose metabolism, conserved adipose tissue, and similarly reduced eGFR. The virological efficacy was similar.
authors.affiliation: Center for Poverty-related Communicable Disorders, Center for Infection and Immunity, and Amsterdam Institute for Global Health and Development, Academic Medical Center, Amsterdam, the Netherlands. s.m.vrouenraets@amc.uva.nl
authors.forename: S M E
authors.initials: SM
authors.lastname: Vrouenraets
authors.forename: F W N M
authors.initials: FW
authors.lastname: Wit
authors.forename: E
authors.initials: E
authors.lastname: Fernandez Garcia
authors.forename: G J
authors.initials: GJ
authors.lastname: Moyle
authors.forename: A G
authors.initials: AG
authors.lastname: Jackson
authors.forename: C
authors.initials: C
authors.lastname: Allavena
authors.forename: F
authors.initials: F
authors.lastname: Raffi
authors.forename: D T
authors.initials: DT
authors.lastname: Jayaweera
authors.forename: S
authors.initials: S
authors.lastname: Mauss
authors.forename: C
authors.initials: C
authors.lastname: Katlama
authors.forename: M
authors.initials: M
authors.lastname: Fisher
authors.forename: L
authors.initials: L
authors.lastname: Slama
authors.forename: W D
authors.initials: WD
authors.lastname: Hardy
authors.forename: E
authors.initials: E
authors.lastname: Dejesus
authors.forename: A
authors.initials: A
authors.lastname: van Eeden
authors.forename: P
authors.initials: P
authors.lastname: Reiss
mesh_terms: D000225:Adenine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D000328:Adult; D000069446:Atazanavir Sulfate; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D004334:Drug Administration Schedule; D050171:Dyslipidemias / Q000139:chemically induced / Q000209:etiology* / Q000378:metabolism; D000068679:Emtricitabine; D005260:Female; D005919:Glomerular Filtration Rate; D015658:HIV Infections / Q000150:complications* / Q000188:drug therapy / Q000378:metabolism*; D006801:Humans; D007674:Kidney Diseases; D008297:Male; D009842:Oligopeptides / Q000008:administration & dosage / Q000493:pharmacokinetics*; D063065:Organophosphonates / Q000008:administration & dosage / Q000493:pharmacokinetics*; D011725:Pyridines / Q000008:administration & dosage / Q000493:pharmacokinetics*; D019258:Saquinavir / Q000008:administration & dosage / Q000493:pharmacokinetics*; D000068698:Tenofovir; D016896:Treatment Outcome
chemical_list: D009842:Oligopeptides; D063065:Organophosphonates; D011725:Pyridines; D003841:Deoxycytidine; D000069446:Atazanavir Sulfate; D000068698:Tenofovir; D000068679:Emtricitabine; D000225:Adenine; D019258:Saquinavir