Jürgen K Rockstroh1, Mark Nelson2, Christine Katlama3, Jay Lalezari4, Josep Mallolas5, Mark Bloch6, Gail V Matthews7, Michael S Saag8, Philippe J Zamor9, Chloe Orkin10, Jacqueline Gress11, Stephanie Klopfer11, Melissa Shaughnessy11, Janice Wahl11, Bach-Yen T Nguyen11, Eliav Barr11, Heather L Platt11, Michael N Robertson11, Mark Sulkowski12. 1. Bonn University Hospital, Bonn, Germany. Electronic address: juergen.rockstroh@ukb.uni-bonn.de. 2. Chelsea and Westminster Hospital, London, UK. 3. Sorbonne Universities, UPMC University of Paris 06, INSERM UMR_S 1136, Pierre Louis Institute of Epidemiology and Public Health, Paris, France; APHP Pitié-Salpêtrière Hospital, Paris, France. 4. Quest Clinical Research, San Francisco, CA, USA. 5. Hospital Clinic-University of Barcelona, Barcelona, Spain. 6. Holdsworth House Medical Practice, Darlinghurst, NSW, Australia. 7. St Vincent's Hospital, Sydney, NSW, Australia. 8. University of Alabama at Birmingham, Birmingham, AL, USA. 9. Division of Hepatology, Carolinas Medical Center, Charlotte, NC, USA. 10. Royal London Hospital, Bart's Health NHS Trust, London, UK. 11. Merck & Co, Inc, Kenilworth, NJ, USA. 12. Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Abstract
BACKGROUND: Hepatitis C virus (HCV) infection is a leading cause of morbidity and mortality in patients with HIV-1. The C-EDGE CO-INFECTION study assessed the efficacy, safety, and tolerability of grazoprevir (MK-5172) plus elbasvir (MK-8742) in patients with HCV and HIV co-infection. METHODS: In this uncontrolled, non-randomised, phase 3, open-label, single-arm study, treatment-naive patients with chronic HCV genotype 1, 4, or 6 infection and HIV co-infection, with or without cirrhosis, were enrolled from 37 centres in nine countries across Europe, the USA, and Australia. Patients were either naive to treatment with any antiretroviral therapy (ART) or stable on ART for at least 8 weeks. All patients received grazoprevir 100 mg plus elbasvir 50 mg in a fixed-dose combination tablet once daily for 12 weeks. The primary endpoint was sustained virological response (HCV RNA <15 IU/mL) 12 weeks after the end of therapy (SVR12). The primary population for efficacy analyses was all patients who received at least one dose of study treatment. This study is registered with ClinicalTrials.gov, number NCT02105662. FINDINGS: Between June 11, 2014, and Aug 29, 2014, 218 patients were enrolled and received grazoprevir plus elbasvir for 12 weeks, all of whom completed follow-up at week 12. SVR12 was achieved by 210 (96%) of 218 patients (95% CI 92·9-98·4). One patient did not achieve SVR12 because of a non-virological reason, and seven patients without cirrhosis relapsed (two subsequently confirmed as reinfections). All 35 patients with cirrhosis achieved SVR12. The most common adverse events were fatigue (29; 13%), headache (27; 12%), and nausea (20; 9%). No patient discontinued treatment because of an adverse event. Two patients receiving ART had transient HIV viraemia. INTERPRETATION: This HCV treatment regimen seems to be effective and well tolerated for patients co-infected with HIV with or without cirrhosis. These data are consistent with previous trials of this regimen in the monoinfected population. This regimen continues to be studied in phase 3 trials. FUNDING: Merck Sharp & Dohme Corp.
BACKGROUND: Hepatitis C virus (HCV) infection is a leading cause of morbidity and mortality in patients with HIV-1. The C-EDGE CO-INFECTION study assessed the efficacy, safety, and tolerability of grazoprevir (MK-5172) plus elbasvir (MK-8742) in patients with HCV and HIV co-infection. METHODS: In this uncontrolled, non-randomised, phase 3, open-label, single-arm study, treatment-naive patients with chronic HCV genotype 1, 4, or 6 infection and HIV co-infection, with or without cirrhosis, were enrolled from 37 centres in nine countries across Europe, the USA, and Australia. Patients were either naive to treatment with any antiretroviral therapy (ART) or stable on ART for at least 8 weeks. All patients received grazoprevir 100 mg plus elbasvir 50 mg in a fixed-dose combination tablet once daily for 12 weeks. The primary endpoint was sustained virological response (HCV RNA <15 IU/mL) 12 weeks after the end of therapy (SVR12). The primary population for efficacy analyses was all patients who received at least one dose of study treatment. This study is registered with ClinicalTrials.gov, number NCT02105662. FINDINGS: Between June 11, 2014, and Aug 29, 2014, 218 patients were enrolled and received grazoprevir plus elbasvir for 12 weeks, all of whom completed follow-up at week 12. SVR12 was achieved by 210 (96%) of 218 patients (95% CI 92·9-98·4). One patient did not achieve SVR12 because of a non-virological reason, and seven patients without cirrhosis relapsed (two subsequently confirmed as reinfections). All 35 patients with cirrhosis achieved SVR12. The most common adverse events were fatigue (29; 13%), headache (27; 12%), and nausea (20; 9%). No patient discontinued treatment because of an adverse event. Two patients receiving ART had transient HIV viraemia. INTERPRETATION: This HCV treatment regimen seems to be effective and well tolerated for patients co-infected with HIV with or without cirrhosis. These data are consistent with previous trials of this regimen in the monoinfected population. This regimen continues to be studied in phase 3 trials. FUNDING: Merck Sharp & Dohme Corp.
Authors: Basile Njei; Thomas R McCarty; Jeffrey Luk; Oforbuike Ewelukwa; Ivo Ditah; Joseph K Lim Journal: J Gastroenterol Hepatol Date: 2016-10 Impact factor: 4.029