title: Effects of ezetimibe on cholesterol metabolism in HIV-infected patients with protease inhibitor-associated dyslipidemia: a single-arm intervention trial.
abstract: BACKGROUND
  The effects of ezetimibe on cholesterol metabolism in HIV-infected patients receiving boosted protease inhibitors have not been thoroughly assessed. The aim of this study was to assess cholesterol homeostasis in patients with PI associated dyslipidemia and its relationship with the response to treatment with the cholesterol-absorption inhibitor ezetimibe.
  
  
  METHODS
  Fifteen patients with ritonavir-boosted PI-containig therapy and LDL-cholesterol > 3.36 mmol/L (>130 mg/dL) were assessed at baseline and after an 8-week course of ezetimibe 10 mg/d. Serum non-cholesterol sterols were measured at each visit as markers of cholesterol synthesis and absorption. Total-, LDL-, and HDL-cholesterol triglycerides, apolipoproteins A1 and B, high sensitivity C-reactive protein, CD4 cells and HIV-1 RNA were also measured.
  
  
  RESULTS
  Ezetimibe treatment was well tolerated in all patients and resulted in significant reductions in total cholesterol (-11.4%, p = .002), LDL-cholesterol (-20.4%, p = .003), non-HDL-cholesterol (-13.4%, p = .002) and apolipoprotein B (-9.1%, p = .021). Treatment with ezetimibe was associated with decreased cholesterol absorption markers (campesterol-to-cholesterol ratio -43.0%, p = .001; sitosterol-to-cholesterol ratio -41.9%, p = .001) and increased synthesis markers (lathosterol-to-cholesterol ratio 53.2%, p = .005). Baseline absorption or synthesis markers were unrelated to the response to treatment. CD4 cell count and plasma HIV-1 RNA remained unchanged.
  
  
  CONCLUSIONS
  The level of cholesterol absorption or synthesis does not appear to be a major determinant of the responsiveness to ezetimibe in patients on ritonavir-boosted PI-containing therapy.
  
  
  BACKGROUND
  EudraCT: 2006-006156-36.
authors.affiliation: Endocrinology and Nutrition Service, Hospital Clínic, Universitat de Barcelona, Villarroel 170, Barcelona 08036, Spain. pleyes@clinic.cat.
authors.forename: Pere
authors.initials: P
authors.lastname: Leyes
authors.forename: Esteban
authors.initials: E
authors.lastname: Martínez
authors.forename: María
authors.initials: M
authors.lastname: Larrousse
authors.forename: Montserrat
authors.initials: M
authors.lastname: Cofán
authors.forename: Joan
authors.initials: J
authors.lastname: Trabal
authors.forename: Ana María
authors.initials: AM
authors.lastname: Pérez-Heras
authors.forename: María T
authors.initials: MT
authors.lastname: Forga
authors.forename: Emilio
authors.initials: E
authors.lastname: Ros
mesh_terms: D000328:Adult; D000368:Aged; D000924:Anticholesteremic Agents / Q000627:therapeutic use; D001384:Azetidines / Q000627:therapeutic use*; D002097:C-Reactive Protein / Q000737:chemistry; D002784:Cholesterol / Q000031:analogs & derivatives / Q000627:therapeutic use; D008078:Cholesterol, LDL / Q000378:metabolism*; D050171:Dyslipidemias / Q000188:drug therapy*; D000069438:Ezetimibe; D005260:Female; D015658:HIV Infections / Q000150:complications* / Q000188:drug therapy; D006801:Humans; D050356:Lipid Metabolism; D008297:Male; D008875:Middle Aged; D010840:Phytosterols / Q000627:therapeutic use; D011480:Protease Inhibitors / Q000009:adverse effects / Q000627:therapeutic use*
chemical_list: D000924:Anticholesteremic Agents; D001384:Azetidines; D008078:Cholesterol, LDL; D010840:Phytosterols; D011480:Protease Inhibitors; C021273:campesterol; C001521:lathosterol; D002097:C-Reactive Protein; D002784:Cholesterol; D000069438:Ezetimibe