Therapy With Ombitasvir/Paritaprevir/Ritonavir Plus Dasabuvir Is Effective and Safe for the Treatment of Genotypes 1 and 4 Hepatitis C Virus (HCV) Infection in Patients With Severe Renal Impairment

A Multicentre Experience

R. Muñoz-Gómez; D. Rincón; A. Ahumada; E. Hernández; M. J. Devesa; S. Izquierdo; M. Ortiz; A. Hernández-Albujar; C. Fernández-Rodríguez; M. Calvo; R. González; M. Lozano; G. Castellano; I. Fernández-Vázquez

Disclosures

J Viral Hepat. 2017;24(6):464-471. 

In This Article

Abstract and Introduction

Abstract

Limited data are available on direct-acting antivirals for treating hepatitis C virus (HCV) infection in patients with severe renal impairment. The aim of this study was to evaluate the effectiveness and safety of ombitasvir/paritaprevir/ritonavir (OBV/PTV/r) ± dasabuvir (DSV) ± ribavirin (RBV) in patients with stage 4 or 5 chronic kidney disease (CKD) and HCV genotype 1 or 4 infection in real clinical practice, and to investigate pharmacological interactions. This retrospective study included patients treated with OBV/PTV/r+DSV±RBV or OBV/PTV/r+RBV with CKD stage 4 (eGFR: 15–29 mL/min/1.73m2) or 5 (eGFR<15 mL/min/1.73m2 or requiring dialysis) and HCV infection by genotypes 1 and 4 between April 2015 and October 2015 in nine Spanish centres. Sustained virological response at 12 weeks (SVR12) was assessed, and clinical and laboratory data, fibrosis stage, adverse events and pharmacological interactions were reported. Forty-six patients were included: 10 (21.7%) had CKD stage 4 and 36 (78.2%) CKD stage 5. Seventeen (36.9%) had cirrhosis. SVR12 rate in the intention-to-treat population was 95.7%. Twenty-one (45.6%) received RBV, which was discontinued in two (9.5%) patients. Anaemia (haemoglobin <10 g/dl) occurred in 12 patients (57.1%) with RBV vs 10 (40.0%) without RBV (P=.246). Renal function remained stable during antiviral therapy. Nine patients (19.5%) experienced serious adverse events unrelated to antiviral therapy. Concomitant medication was discontinued or modified in 41.3% of patients. In conclusion, the effectiveness of OBV/PTV/r±DSV±RBV in patients with CKD 4–5 was similar to that observed in those with normal renal function and was not associated with severe adverse events.

Introduction

Chronic hepatitis C virus (HCV) infection is a major problem worldwide.[1] It has become evident that patients with renal disease and/or on haemodialysis are among those with a higher risk of HCV infection.[2,3] It is well known that HCV infection in patients with renal dysfunction increases morbidity and mortality due to liver disease, while chronic HCV infection contributes to deteriorate renal function.[4]

The use of conventional interferon-based therapies in patients with advanced CKD has been associated with low efficacy and high toxicity.[5] Recent development of direct-acting antiviral agents (DAAs) has dramatically changed the treatment of chronic hepatitis C, and interferon-free regimes have become the treatment of choice in clinical practice.[6]

Information on the efficacy and safety of DAAs in patients with renal failure is limited. As sofosbuvir and its metabolites (GS-331007) are excreted by the kidney, available data do not support its use when glomerular filtration rates are <30 mL/min.[7,8] Recently, the FDA has approved ombitasvir/paritaprevir/ritonavir plus dasabuvir (OBV/PTV/r+DSV) for the treatment of patients with severe renal disease, as the metabolism of these compounds is mediated predominantly by the liver.[9] Therapy with OBV/PTV/r+DSV ± RBV is currently approved for the treatment of patients infected with HCV genotype (GT) 1, based on the results of several clinical trials in which SVR rates at week 12 (SVR12) reached 95%-100%.[10–17] A regimen without dasabuvir (OBV/PTV/r) is indicated to treat infection by HCV GT4, with 91%-100% SVR12 in RBV-free and RBV-containing combinations for treatment-naïve and treatment-experienced patients.[18]

Pharmacokinetic studies of OBV/PTV/r+DSV in patients with renal impairment indicate that no dose adjustments are needed in this population,[19] but clinical data are very scarce. One recent prospective clinical trial evaluated the use of OBV/PTV/r+DSV ± RBV in 20 GT1-infected patients with CKD4 (estimated glomerular filtration rate [eGFR]=15–29 mL/min/1.73 m2) or CKD5 (eGFR < 15 mL/min/1.73 m2 or receiving dialysis) reporting excellent results: 100% of patients completing treatment and 90% reaching a SVR12.[20] However, no studies in real-life clinical experience with OBV/PTV/r+DSV in this setting have been published, and data on the effectiveness and safety of OBV/PTV/r in GT4-infected patients with advanced CKD are lacking.

In this report, we analyse the effectiveness and safety of OBV/PTV/r+DSV ± RBV or OBV/PTV/r + RBV in patients with CKD stage 4 or 5 and HCV GT1 or GT4 infection in real clinical practice. Secondary objectives included the evaluation of renal function during treatment and follow-up, and the management of anaemia and drug interactions.

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