title: 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 (C12h) 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 C12h 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.
authors: From the 1 Department of Medical and Surgical Sciences, Clinics of Infectious Diseases.
authors: Leonardo
authors: L
authors: Calza
authors: Ilaria
authors: I
authors: Danese
authors: Vincenzo
authors: V
authors: Colangeli
authors: Roberto
authors: R
authors: Manfredi
authors: Eleonora
authors: E
authors: Magistrelli
authors: Gabriella
authors: G
authors: Verucchi
authors: Matteo
authors: M
authors: Conti
authors: Roberto
authors: R
authors: Motta
authors: Pierluigi
authors: P
authors: Viale
mesh_terms: D000328:Adult; D000480:Alkynes; D000704:Analysis of Variance; D019380:Anti-HIV Agents / Q000097:blood* / Q000627:therapeutic use; D048588:Benzoxazines / Q000097:blood* / Q000493:pharmacokinetics / Q000627:therapeutic use; D060085:Coinfection / Q000188:drug therapy / Q000453:epidemiology; D003521:Cyclopropanes; D000069454:Darunavir / Q000097:blood* / Q000493:pharmacokinetics / Q000627:therapeutic use; D005260:Female; D015658:HIV Infections / Q000150:complications / Q000188:drug therapy* / Q000453:epidemiology; D006526:Hepatitis C / Q000150:complications* / Q000453:epidemiology; D006801:Humans; D008111:Liver Function Tests; D008297:Male; D008875:Middle Aged; D000068898:Raltegravir Potassium / Q000097:blood* / Q000493:pharmacokinetics / Q000627:therapeutic use; D019438:Ritonavir / Q000097:blood* / Q000493:pharmacokinetics / Q000627:therapeutic use
chemical_list: D000480:Alkynes; D019380:Anti-HIV Agents; D048588:Benzoxazines; D003521:Cyclopropanes; D000068898:Raltegravir Potassium; C098320:efavirenz; D019438:Ritonavir; D000069454:Darunavir
keywords: Pharmacokinetics; integrase inhibitor; liver function; non-nucleoside reverse transcriptase inhibitor; protease inhibitor