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Mericitabine and ritonavir‐boosted danoprevir with or without ribavirin in treatment‐naive HCV genotype 1 patients: INFORM ‐ SVR study
Author(s) -
Gane Edward J.,
Pockros Paul J.,
Zeuzem Stefan,
Marcellin Patrick,
Shikhman Anna,
Bernaards Coen,
Zhou Julian,
Yetzer Ellen S.,
Ballester Rosa,
Dwyer Cindy,
Tong Xiao,
Nájera Isabel,
Bertasso Anne,
Hammond Janet,
Kindrick Amy,
Morcos Peter N.,
Smith Patrick,
Stancic Saray,
Shulman Nancy S.
Publication year - 2015
Publication title -
liver international
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.873
H-Index - 110
eISSN - 1478-3231
pISSN - 1478-3223
DOI - 10.1111/liv.12588
Subject(s) - medicine , ribavirin , tolerability , ritonavir , gastroenterology , resistance mutation , hepatitis c virus , virology , viral load , adverse effect , virus , biology , reverse transcriptase , rna , biochemistry , antiretroviral therapy , gene
Background & Aims Safety and tolerability of peginterferon‐based hepatitis C virus ( HCV ) infection therapy remains suboptimal, even when direct‐acting antiviral agents are added. This study assessed the efficacy, safety and tolerability of mericitabine combined with ritonavir‐boosted danoprevir (danoprevir/r) ± ribavirin for up to 24 weeks in treatment‐naïve HCV genotype (G)1 infected patients. Methods Patients received twice daily mericitabine (1000 mg) and danoprevir/r (100 mg/100 mg) plus either ribavirin (1000/1200 mg/day; Arm A) or placebo (Arm B) for 12 or 24 weeks. Patients with HCV RNA <43 IU/ ml between Weeks 2 and 8 and HCV RNA <15 IU/ ml at Week 10 were rerandomized (1:1) at Week 12 to discontinue/continue assigned regimens until Week 24. Because of unacceptable relapse rates in both 12‐week arms and in ribavirin‐free Arm B, treatment was extended to 24 weeks and patients in Arm B received peginterferon alfa‐2a/ribavirin. The primary outcome was sustained virological response 24 weeks after end of treatment (SVR24). Results In Arm A, the SVR 24 rate in patients receiving 24 weeks of therapy was 37.9% (25/66); 63.6% (14/22) in G1b and 25.0% (11/44) in G1a patients. Virologic breakthrough and relapse were associated with danoprevir‐resistant virus in most cases. The mericitabine‐resistance mutation ( NS 5 BS 282T) was detected in two patients bearing dual resistant virus NS 3 R155K/ NS 5B S282T and dual resistance mutation L159F/L320F in one patient. Treatment was safe and well tolerated. Conclusions Mericitabine, danoprevir/r plus ribavirin for 24 weeks were safe and well tolerated. However, SVR rates were poor, achieving rates of only 25.0% in G1a and 63.6% in G1b patients.