BACKGROUND: Genotype 1b (GT1b) is the most common subtype of the hepatitis C virus (HCV). We present an integrated analysis of 1070 participants with HCV GT1b infection from 30 countries who received elbasvir/grazoprevir for 12 weeks. METHODS: This is a retrospective analysis of data from participants with chronic HCV GT1b infection enrolled in 11 phase II/III clinical trials. All participants received elbasvir 50 mg plus grazoprevir 100 mg once daily for 12 weeks. The primary end point of all studies was sustained virologic response 12 weeks after completion of therapy (SVR12, HCV RNA < 15 IU/ml). RESULTS: SVR12 was 97.2% (1040/1070). Of the 30 participants who failed to attain SVR12, 15 relapsed and 15 had nonvirologic failure. Among participant subgroups, SVR12 was high in those with compensated cirrhosis (188/189, 99.5%), HIV co-infection (51/54, 94.4%), and baseline viral load > 800,000 IU/ml (705/728, 96.8%). Resistance-associated substitutions (RASs) at NS5A positions 28, 30, 31, or 93 were present in 21.6% of participants at baseline. SVR12 was 99.6% (820/823) in participants without baseline NS5A RASs and 94.7% (215/227) in those with baseline NS5A RASs. Serious adverse events occurred in 3.2% (34/1070) of participants, nine of which occurred after study medication was completed. CONCLUSIONS: Elbasvir/grazoprevir for 12 weeks represents an effective treatment option for participants with HCV GT1b infection. SVR12 was high in all participant subgroups, including those with compensated cirrhosis, HIV co-infection, and high baseline viral load. CLINICALTRIALS. GOV IDENTIFIERS: The trials discussed in this paper were registered with Clinicaltrial.gov as the following: NCT02092350 (C-SURFER), NCT02105662 (C-EDGE Co-Infection), NCT02105467 (C-EDGE treatment-naive), NCT02105701 (C-EDGE treatment-experienced), NCT01717326 (C-WORTHy), NCT02251990 (C-CORAL), NCT02105688 (C-EDGE COSTAR), NCT02252016 (C-EDGE IBLD), NCT02115321 (C-SALT), NCT02203149 (Japan phase 2/3 study), NCT02358044 (C-EDGE Head-2-Head).

AW Morrow Gastroenterology and Liver Centre Royal Prince Alfred Hospital Sydney NSW Australia

Baylor College of Medicine Advanced Liver Therapies Houston TX USA

Department of Gastroenterology and Hepatology Royal Perth Hospital Perth WA Australia

Department of Hepatology Toranomon Hospital Tokyo Japan

Goethe University Hospital Theodor Stern Kai 7 60590 Frankfurt Germany

Institute for Clinical and Experimental Medicine Prague Czech Republic

Merck and Co Inc Kenilworth NJ USA

Service d'Hépatologie Hôpital Saint Antoine Université Pierre and Marie Curie Paris France

Storr Liver Centre Westmead Institute for Medical Research Westmead Hospital and University of Sydney Sydney NSW Australia

Zobrazit více v PubMed

J Hepatol. 2015 Jul;63(1):199-236 PubMed

Lancet HIV. 2015 Aug;2(8):e319-27 PubMed

J Gastroenterol. 2017 Apr;52(4):520-533 PubMed

Ann Intern Med. 2015 Jul 7;163(1):1-13 PubMed

ChemMedChem. 2013 Dec;8(12):1930-40 PubMed

N Engl J Med. 2015 Dec 31;373(27):2599-607 PubMed

Ann Intern Med. 2016 Nov 1;165(9):625-634 PubMed

Adv Ther. 2016 Jul;33(7):1169-79 PubMed

N Engl J Med. 2014 May 15;370(20):1889-98 PubMed

Lancet. 2015 Mar 21;385(9973):1087-97 PubMed

Gastroenterology. 2017 Jan;152(1):164-175.e4 PubMed

Hepatology. 2015 Sep;62(3):932-54 PubMed

Liver Int. 2016 Oct;36(10 ):1433-41 PubMed

J Hepatol. 2016 Dec;65(6):1112-1119 PubMed

N Engl J Med. 2014 May 15;370(20):1879-88 PubMed

Antimicrob Agents Chemother. 2012 Aug;56(8):4161-7 PubMed

Lancet. 2015 Mar 21;385(9973):1075-86 PubMed

Gastroenterology. 2014 Aug;147(2):359-365.e1 PubMed

J Hepatol. 2014 Nov;61(1 Suppl):S45-57 PubMed

Lancet. 2015 Oct 17;386(10003):1537-45 PubMed

Zobrazit více v PubMed

ClinicalTrials.gov
NCT02358044