title: Efficacy and safety of grazoprevir (MK-5172) and elbasvir (MK-8742) in patients with hepatitis C virus and HIV co-infection (C-EDGE CO-INFECTION): a non-randomised, open-label trial.
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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
  
  
  BACKGROUND
  Merck Sharp & Dohme Corp.
authors.affiliation: Bonn University Hospital, Bonn, Germany. Electronic address: juergen.rockstroh@ukb.uni-bonn.de.
authors.forename: Jürgen K
authors.initials: JK
authors.lastname: Rockstroh
authors.affiliation: Chelsea and Westminster Hospital, London, UK.
authors.forename: Mark
authors.initials: M
authors.lastname: Nelson
authors.affiliation: 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.
authors.forename: Christine
authors.initials: C
authors.lastname: Katlama
authors.affiliation: Quest Clinical Research, San Francisco, CA, USA.
authors.forename: Jay
authors.initials: J
authors.lastname: Lalezari
authors.affiliation: Hospital Clinic-University of Barcelona, Barcelona, Spain.
authors.forename: Josep
authors.initials: J
authors.lastname: Mallolas
authors.affiliation: Holdsworth House Medical Practice, Darlinghurst, NSW, Australia.
authors.forename: Mark
authors.initials: M
authors.lastname: Bloch
authors.affiliation: St Vincent's Hospital, Sydney, NSW, Australia.
authors.forename: Gail V
authors.initials: GV
authors.lastname: Matthews
authors.affiliation: University of Alabama at Birmingham, Birmingham, AL, USA.
authors.forename: Michael S
authors.initials: MS
authors.lastname: Saag
authors.affiliation: Division of Hepatology, Carolinas Medical Center, Charlotte, NC, USA.
authors.forename: Philippe J
authors.initials: PJ
authors.lastname: Zamor
authors.affiliation: Royal London Hospital, Bart's Health NHS Trust, London, UK.
authors.forename: Chloe
authors.initials: C
authors.lastname: Orkin
authors.affiliation: Merck & Co, Inc, Kenilworth, NJ, USA.
authors.forename: Jacqueline
authors.initials: J
authors.lastname: Gress
authors.affiliation: Merck & Co, Inc, Kenilworth, NJ, USA.
authors.forename: Stephanie
authors.initials: S
authors.lastname: Klopfer
authors.affiliation: Merck & Co, Inc, Kenilworth, NJ, USA.
authors.forename: Melissa
authors.initials: M
authors.lastname: Shaughnessy
authors.affiliation: Merck & Co, Inc, Kenilworth, NJ, USA.
authors.forename: Janice
authors.initials: J
authors.lastname: Wahl
authors.affiliation: Merck & Co, Inc, Kenilworth, NJ, USA.
authors.forename: Bach-Yen T
authors.initials: BY
authors.lastname: Nguyen
authors.affiliation: Merck & Co, Inc, Kenilworth, NJ, USA.
authors.forename: Eliav
authors.initials: E
authors.lastname: Barr
authors.affiliation: Merck & Co, Inc, Kenilworth, NJ, USA.
authors.forename: Heather L
authors.initials: HL
authors.lastname: Platt
authors.affiliation: Merck & Co, Inc, Kenilworth, NJ, USA.
authors.forename: Michael N
authors.initials: MN
authors.lastname: Robertson
authors.affiliation: Johns Hopkins University School of Medicine, Baltimore, MD, USA.
authors.forename: Mark
authors.initials: M
authors.lastname: Sulkowski
mesh_terms: D000328:Adult; D000577:Amides; D000998:Antiviral Agents / Q000008:administration & dosage*; D001315:Australia; D001572:Benzofurans / Q000008:administration & dosage* / Q000009:adverse effects / Q000627:therapeutic use; D002219:Carbamates; D060085:Coinfection / Q000188:drug therapy / Q000821:virology; D003521:Cyclopropanes; D004334:Drug Administration Schedule; D004338:Drug Combinations; D004359:Drug Therapy, Combination; D005060:Europe; D005260:Female; D005838:Genotype; D015658:HIV Infections / Q000150:complications* / Q000188:drug therapy*; D015497:HIV-1 / Q000187:drug effects; D016174:Hepacivirus / Q000187:drug effects; D019698:Hepatitis C, Chronic / Q000150:complications* / Q000188:drug therapy*; D006801:Humans; D007093:Imidazoles / Q000008:administration & dosage* / Q000009:adverse effects / Q000627:therapeutic use; D008103:Liver Cirrhosis / Q000188:drug therapy / Q000821:virology; D008297:Male; D008875:Middle Aged; D011810:Quinoxalines / Q000008:administration & dosage* / Q000009:adverse effects / Q000627:therapeutic use; D012367:RNA, Viral / Q000235:genetics; D013449:Sulfonamides; D016896:Treatment Outcome; D014481:United States; D019562:Viral Load; D047029:Lactams, Macrocyclic
chemical_list: D000577:Amides; D000998:Antiviral Agents; D001572:Benzofurans; D002219:Carbamates; D003521:Cyclopropanes; D004338:Drug Combinations; D007093:Imidazoles; D011810:Quinoxalines; D012367:RNA, Viral; D013449:Sulfonamides; C578009:grazoprevir; D047029:Lactams, Macrocyclic; C000589335:elbasvir