title: Saquinavir exposure in HIV-infected patients with chronic viral hepatitis.
abstract: OBJECTIVE
  The aim of this study was to assess the influence of hepatitis B virus or hepatitis C virus co-infection and the extent of liver fibrosis on saquinavir and ritonavir pharmacokinetics in HIV-infected subjects without liver function impairment.
  
  
  METHODS
  A cross-sectional, comparative study enrolling HIV-infected adults receiving saquinavir/ritonavir 1000/100 mg twice daily or 1500/100 mg once daily was conducted. Patients with chronic viral hepatitis (HEP+) were grouped as having advanced liver fibrosis (HEP+/FIB+) or not (HEP+/FIB-) based on the FIB-4 index. Saquinavir and ritonavir trough concentrations (C(trough)) in plasma were determined by HPLC. The geometric mean ratio (GMR) was used to compare saquinavir and ritonavir C(trough) between HEP- and HEP+ patients, and the influence of the extent of liver fibrosis on saquinavir and ritonavir pharmacokinetics was explored using analysis of variance.
  
  
  RESULTS
  One hundred and thirty-eight patients on twice-daily saquinavir/ritonavir (67 HEP-, 71 HEP+) and 36 patients on once-daily saquinavir/ritonavir (12 HEP-, 24 HEP+) were included. Saquinavir C(trough) was comparable between HEP- and HEP+ patients receiving either saquinavir/ritonavir 1000/100 mg twice daily [GMR 0.91, 95% confidence interval (CI) 0.60-1.37; P = 0.655] or 1500/100 mg once daily (GMR 0.88, 95% CI 0.39-1.97; P = 0.752). Similarly, ritonavir C(trough) was also comparable between HEP- and HEP+ patients. The extent of liver fibrosis was not significantly related to saquinavir or ritonavir C(trough) in patients receiving either of the two studied doses.
  
  
  CONCLUSIONS
  Saquinavir C(trough) was not increased in HIV-infected patients with chronic viral hepatitis in the absence of liver function impairment. These results confirm that no specific dose modification of saquinavir/ritonavir should be recommended in this setting.
authors.affiliation: 'Lluita contra la SIDA' Foundation, Hospital Universitari Germans Trias i Pujol, Badalona, Spain. jmolto@flsida.org
authors.forename: José
authors.initials: J
authors.lastname: Moltó
authors.forename: Josep Maria
authors.initials: JM
authors.lastname: Llibre
authors.forename: Esteban
authors.initials: E
authors.lastname: Ribera
authors.forename: Carlos
authors.initials: C
authors.lastname: Mínguez
authors.forename: Jesús Sánchez
authors.initials: JS
authors.lastname: del Río
authors.forename: Enric
authors.initials: E
authors.lastname: Pedrol
authors.forename: Gabriel
authors.initials: G
authors.lastname: Vallecillo
authors.forename: Samandhy
authors.initials: S
authors.lastname: Cedeño
authors.forename: Marta
authors.initials: M
authors.lastname: Valle
authors.forename: Cristina
authors.initials: C
authors.lastname: Miranda
authors.forename: Eugenia
authors.initials: E
authors.lastname: Negredo
authors.forename: Bonaventura
authors.initials: B
authors.lastname: Clotet
mesh_terms: D000328:Adult; D019380:Anti-HIV Agents / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000627:therapeutic use; D002851:Chromatography, High Pressure Liquid; D003430:Cross-Sectional Studies; D005260:Female; D015658:HIV Infections / Q000150:complications* / Q000188:drug therapy*; D006525:Hepatitis, Viral, Human / Q000150:complications* / Q000188:drug therapy*; D006801:Humans; D008103:Liver Cirrhosis / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D010949:Plasma / Q000737:chemistry; D019438:Ritonavir / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use; D019258:Saquinavir / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000627:therapeutic use
chemical_list: D019380:Anti-HIV Agents; D019258:Saquinavir; D019438:Ritonavir