부산대학교 도서관

OBJECTIVES: 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 (Ctrough) in plasma were determined by HPLC. The geometric mean ratio (GMR) was used to compare saquinavir and ritonavir Ctrough 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 Ctrough 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 Ctrough was also comparable between HEP− and HEP+ patients. The extent of liver fibrosis was not significantly related to saquinavir or ritonavir Ctrough in patients receiving either of the two studied doses. CONCLUSIONS: Saquinavir Ctrough 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.