Douglas Dieterich1, Mark Nelson, Vicente Soriano, Keikawus Arastéh, Josep M Guardiola, Jürgen K Rockstroh, Sanjay Bhagani, Montserrat Laguno, Cristina Tural, Patrick Ingiliz, Mamta K Jain, Jerry O Stern, Montserrat Manero, Richard Vinisko, Jens Kort. 1. aIcahn School of Medicine at Mount Sinai, New York, USA bChelsea and Westminster Hospital, London, UK cHospital Carlos III, Madrid, Spain dEPIMED, Vivantes Auguste-Viktoria-Klinikum, Berlin, Germany eHospital de la Santa Creu i Sant Pau, Barcelona, Spain fUniversity of Bonn, Bonn, Germany gRoyal Free Hospital, London, UK hHospital Clínic iHospital Universitari Germans Trias i Pujol and Universitat Autònoma de Barcelona, Barcelona, Spain jMedizinisches Infektiologiezentrum Berlin (MIB), Berlin, Germany kUT Southwestern Medical Center, Dallas, Texas lBoehringer Ingelheim Pharmaceuticals Inc., Ridgefield, Connecticut, USA mBoehringer Ingelheim España S.A., Barcelona, Spain.
Abstract
OBJECTIVE:Faldaprevir is a potent, once-daily hepatitis C virus (HCV) NS3/4A protease inhibitor. STARTVerso4 assessed the efficacy and safety of faldaprevir and response-guidedpegylated interferon α-2a/ribavirin (PegIFN/RBV) in individuals with HCV/HIV co-infection. DESIGN: A phase 3 open-label study (NCT01399619). METHODS:Individuals (N = 308) co-infected with HCV genotype 1 (treatment-naive or prior interferon relapsers) and HIV [96% on antiretroviral therapy (ART)] received faldaprevir 120 mg (N = 123) or 240 mg (N = 185) and PegIFN/RBV. Those receiving a protease inhibitor or efavirenz ART were assigned to faldaprevir 120 or 240 mg, respectively. Individuals achieving early treatment success (ETS; HCV RNA <25 IU/ml at week 4 and undetectable at week 8) were randomized to 24 or 48 weeks of PegIFN/RBV. The primary endpoint was sustained virologic response 12 weeks after treatment (SVR12). RESULTS:SVR12 was achieved in 221 (72%) individuals, and the rates were comparable across faldaprevir doses. ETS was achieved in 80%, and of these 86% achieved SVR12, with comparable rates with 24 and 48 weeks of PegIFN/RBV (87 and 94%, respectively). In multivariate analysis, age below 40 years, IL28B CC genotype, and baseline HCV RNA below 800 000 IU/ml were associated with SVR12 (P = 0.027, P < 0.0001, and P = 0.0002, respectively), whereas treatment (ART regimen and faldaprevir dose), liver cirrhosis, and genotype 1 subtype were not. The safety profile was comparable to that of faldaprevir in HCV-monoinfected individuals. CONCLUSIONS:High SVR12 rates were achieved with faldaprevir and PegIFN/RBV in HIV/HCV co-infected individuals, regardless of faldaprevir dose and background ART, HCV genotype 1 subtype, or cirrhosis status. SVR rates mirrored those obtained with similar regimens in HCV monoinfected individuals.
RCT Entities:
OBJECTIVE:Faldaprevir is a potent, once-daily hepatitis C virus (HCV) NS3/4A protease inhibitor. STARTVerso4 assessed the efficacy and safety of faldaprevir and response-guided pegylated interferon α-2a/ribavirin (PegIFN/RBV) in individuals with HCV/HIV co-infection. DESIGN: A phase 3 open-label study (NCT01399619). METHODS: Individuals (N = 308) co-infected with HCV genotype 1 (treatment-naive or prior interferon relapsers) and HIV [96% on antiretroviral therapy (ART)] received faldaprevir 120 mg (N = 123) or 240 mg (N = 185) and PegIFN/RBV. Those receiving a protease inhibitor or efavirenz ART were assigned to faldaprevir 120 or 240 mg, respectively. Individuals achieving early treatment success (ETS; HCV RNA <25 IU/ml at week 4 and undetectable at week 8) were randomized to 24 or 48 weeks of PegIFN/RBV. The primary endpoint was sustained virologic response 12 weeks after treatment (SVR12). RESULTS: SVR12 was achieved in 221 (72%) individuals, and the rates were comparable across faldaprevir doses. ETS was achieved in 80%, and of these 86% achieved SVR12, with comparable rates with 24 and 48 weeks of PegIFN/RBV (87 and 94%, respectively). In multivariate analysis, age below 40 years, IL28B CC genotype, and baseline HCV RNA below 800 000 IU/ml were associated with SVR12 (P = 0.027, P < 0.0001, and P = 0.0002, respectively), whereas treatment (ART regimen and faldaprevir dose), liver cirrhosis, and genotype 1 subtype were not. The safety profile was comparable to that of faldaprevir in HCV-monoinfected individuals. CONCLUSIONS: High SVR12 rates were achieved with faldaprevir and PegIFN/RBV in HIV/HCV co-infected individuals, regardless of faldaprevir dose and background ART, HCV genotype 1 subtype, or cirrhosis status. SVR rates mirrored those obtained with similar regimens in HCV monoinfected individuals.
Authors: K L Berger; J Scherer; M Ranga; N Sha; J O Stern; A-M Quinson; G Kukolj Journal: Antimicrob Agents Chemother Date: 2015-07-20 Impact factor: 5.191
Authors: Mark Hull; Stephen Shafran; Alex Wong; Alice Tseng; Pierre Giguère; Lisa Barrett; Shariq Haider; Brian Conway; Marina Klein; Curtis Cooper Journal: Can J Infect Dis Med Microbiol Date: 2016-07-04 Impact factor: 2.471