Efficacy of a 12-Week Simeprevir Plus Peginterferon/Ribavirin (PR) Regimen in Treatment-Naïve Patients with Hepatitis C Virus (HCV) Genotype 4 (GT4) Infection and Mild-To-Moderate Fibrosis Displaying Early On-Treatment Virologic Response

Abstract

BackgroundHCV GT4 accounts for up to 20% of HCV infections worldwide. Simeprevir, given for 12 weeks as part of a 24- or 48-week combination regimen with PR is approved for the treatment of chronic HCV GT4 infection. Primary study objectives were assessment of efficacy and safety of simeprevir plus PR in treatment-naïve patients with HCV GT4 treated for 12 weeks. Primary efficacy outcome was sustained virologic response 12 weeks post-treatment (SVR12). Additional objectives included investigation of potential associations of rapid virologic response and baseline factors with SVR12.MethodsThis multicentre, open-label, single-arm study (NCT01846832) evaluated efficacy and safety of simeprevir plus PR in 67 patients with HCV GT4 infection. Patients were treatment-naïve, aged 18–70 years with METAVIR F0–F2 fibrosis. Patients with early virologic response (HCV RNA <25 IU/mL [detectable/undetectable in IL28B CC patients or undetectable in IL28B CT/TT patients] at Week 2 and undetectable at Weeks 4 and 8) were eligible to stop all treatment at the end of Week 12, otherwise PR therapy was continued to Week 24.ResultsOf 67 patients treated, 34 (51%) qualified for 12-week treatment including all but one patient with IL28B CC genotype (14/15). All patients in the 12-week group had undetectable HCV RNA at end of treatment, and 97% (33/34) achieved SVR12. No new safety signals with simeprevir plus PR were identified. The proportion of patients experiencing Grade 3–4 adverse events was lower in the 12-week group than in the 24-week group.ConclusionsOur findings on simeprevir plus PR therapy shortened to 12 weeks in patients with HCV GT4 infection with favourable baseline characteristics and displaying early on-treatment virologic response are encouraging. No new safety signals were associated with simeprevir plus PR in this study.Trial RegistrationNCT01846832

Treatment of hepatitis C virus genotype 4 in the DAA era

“…The results of this analysis show the pivotal role of OBV/PTV/r, which is characterized by a SVR rate higher than 90% in all categories of patients [ 17 , 27 – 30 ] and studied for GT4 also in the context of advanced kidney disease [ 35 , 36 ]. Likewise SOF/LDV and SMV + SOF achieve high success rates [ 11 , 14 – 16 , 21 – 26 , 28 , 34 – 36 ]. We must also consider promising results obtained with EBR + GZR [ 17 , 32 ], glicaprevir/biprentasvir [ 19 , 20 , 42 ] and SOF/VEL in association or not with VOX [ 8 – 11 ].…”

“…In a multicenter study, Asselah et al investigated the efficacy and safety of 12-week SMV plus peg-IFN/RBV in 67 treatment-naïve patients with GT4 infection and F0-F2 fibrosis [ 26 ]. Patients with early virologic response (HCV RNA < 25 IU/mL) at Week 2 and HCV RNA undetectable at weeks 4 and 8 were eligible to stop all treatment at the end of week 12 ( n = 34), otherwise Peg-IFN/RBV therapy was continued to week 24.…”

ITPA gene polymorphism (94C>A) effects on ribavirin‐induced anemia during therapy in Egyptian patients with chronic hepatitis C

“…Treatment regimen of HCV genotype 4 with PEG‐IFN‐alfa/RBV requires 48‐weeks and accomplishes SVR rates of 43‐70%. Patients with HCV genotype 1 require a 48 week treatment regimen and a standard dose of RBV; while those with HCV genotype 2 or 3 appear to be adequately treated with a low dose of RBV for 24 weeks …”

Eliminating hepatitis C within low-income countries – The need to cure genotypes 4, 5, 6

“…43 The addition of simeprevir to PegIFN and RBV, in a response-guided therapy, leads also increased SVR. 44 Interferon-free sofosbuvir-RBV was used for 12 or 24 weeks in clinical trials in Egyptian patients with GT4 infection, in the US 45 and Egypt. 46 Twelve-week treatment was associated with suboptimal response (SVR at 12 weeks [SVR12] 68%-77%) and treatment for 24 weeks was associated with SVR rates of 90%-93%.…”