Plasma concentrations of efavirenz, darunavir/ritonavir and raltegravir in HIV-HCV-coinfected patients without liver cirrhosis in comparison with HIV-monoinfected patients

Abstract

Background: The objective of the study was to assess plasma concentrations of efavirenz, darunavir/ritonavir and raltegravir in patients with human immunodeficiency virus-hepatitis C virus (HIV-HCV)-coinfection without liver cirrhosis. Methods: In this observational, open-label study, adult HIV-infected outpatients treated with tenofovir/emtricitabine plus efavirenz (600 mg daily), darunavir/ritonavir (800/100 mg daily) or raltegravir (400 mg twice daily) for at least 4 weeks were asked to participate. Subjects with liver cirrhosis were excluded. The trough concentration (C_trough) of darunavir/ritonavir and raltegravir and the mid-dose concentration (C_12h) of efavirenz were assessed at steady state by a validated high-performance liquid chromatography (HPLC)-tandem mass spectrometry method. Results: A total of 96 HIV-positive patients were enrolled into the study. Thirty-four patients were treated with efavirenz, 33 with darunavir/ritonavir and 29 with raltegravir. The geometric mean plasma C_trough [coefficient of variation (%)] of darunavir was comparable between HIV+/HCV+ and HIV+/HCV– subjects: 2644 ng/ml (155%) and 2491 ng/ml (139%), respectively (geometric mean ratio (GMR) = 0.81; 95% confidence interval (CI) = 0.79–1.56; p = 0.69). These values were comparable for raltegravir: 108 ng/ml (149%) in the HIV+/HCV+ group and 96 ng/ml (161%) in the HIV+/HCV– group (GMR = 0.84; 95% CI = 0.61–1.44; p = 0.72). On the contrary, the geometric mean plasma C_12h of efavirenz was significantly higher among the 15 HIV+/HCV+ patients (1915 ng/ml, 159%) than among the 19 HIV+/HCV– patients (1505 ng/ml, 167%; GMR = 1.41; 95% CI = 1.19–1.71; p = 0.009). Conclusions: The mean plasma concentration of efavirenz was significantly higher in HCV-positive than in HCV-negative patients without liver cirrhosis, while the mean plasma levels of darunavir/ritonavir and raltegravir were comparable in both groups.

Keywords::

• Pharmacokinetics
• liver function
• protease inhibitor
• non-nucleoside reverse transcriptase inhibitor
• integrase inhibitor

Declaration of interest: The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.