• Maarten J Deenen, Clara T M M de Kanter, Anthonius S M Dofferhoff, Karin J T Grintjes-Huisman, Andre J A M van der Ven, Hanneke W H A Fleuren, Elizabeth H Gisolf, Peter P Koopmans, Joost P H Drenth, and David M Burger.
• *Department of Pharmacy, Radboud University Medical Center, Nijmegen; †Department of Clinical Pharmacy, Rijnstate Hospital, Arnhem; ‡Nijmegen Institute for Health Sciences, Radboud University Medical Center, Nijmegen; §Department of General Internal Medicine, Radboud University Medical Center, Nijmegen; ¶Department of Internal Medicine, Canisius Wilhelmina Hospital, Nijmegen; ‖Department of Clinical Pharmacy, Canisius Wilhelmina Hospital, Nijmegen; **Department of Internal Medicine, Rijnstate Hospital, Arnhem; and ††Department of Internal Medicine, Division of Gastroenterology and Hepatology, Radboud University Medical Center, Nijmegen, the Netherlands.

BackgroundHepatitis C virus (HCV)/HIV-coinfected patients respond worse to dual therapy with ribavirin (RBV)/peginterferon compared with HCV-monoinfected patients. Several trials found that lower RBV plasma concentrations are associated with impaired virological response rates. The aim of this study was to determine RBV plasma concentrations in a cohort of HCV-monoinfected and HCV/HIV-coinfected patients. Our hypothesis is that HCV/HIV-coinfected patients have lower RBV plasma concentrations, which may in part explain their inferior response to dual therapy.MethodsA retrospective cohort study was performed in chronic HCV-monoinfected and HCV/HIV-coinfected patients who received peginterferon and weight-based RBV. Plasma RBV concentrations were determined at weeks 4 and 12 by a validated high-performance liquid chromatography assay. RBV concentrations were compared between monoinfected and coinfected patients. We calculated the proportion of patients with a subtherapeutic RBV plasma concentration defined as <2.0 mg/L.ResultsA total of 61 HCV-infected patients were included, of whom 21 (34%) were coinfected with HIV. Although there was no difference in the weight-based dose of RBV between monoinfected and coinfected patients, RBV exposure was significantly lower in HCV/HIV-coinfected patients than in HCV-monoinfected patients: the mean ± SD RBV plasma concentrations were 1.82 ± 0.63 mg/L versus 2.25 ± 0.80 mg/L (P = 0.04) at week 4 and 2.14 ± 0.65 mg/L versus 2.62 ± 0.81 mg/L (P = 0.05) at week 12, respectively. The percentage of patients with subtherapeutic plasma concentrations of RBV in coinfected patients versus monoinfected patients was 62% versus 46% (P = 0.240) at week 4 and 50% versus 16% (P = 0.01) at week 12 of treatment, respectively.ConclusionsHIV/HCV-coinfected patients yield significantly lower plasma concentrations of RBV than HCV-monoinfected patients. This puts them at an increased risk of not achieving sustained virological response.

0 keywords...

hide…