Ombitasvir/paritaprevir/ritonavir+dasabuvir+ribavirin for chronic hepatitis C virus genotype 1b-infected cirrhotics (TURQUOISE-IV).

OBJECTIVE: An estimated 336 per 100 000 people in Russia are infected with hepatitis C virus, including up to 75% with genotype (GT) 1b. In the TURQUOISE-II/-III trials, a 12-week regimen of the direct-acting antiviral agents ombitasvir (OBV), paritaprevir (PTV), ritonavir, and dasabuvir (DSV) in GT1b-infected patients with compensated cirrhosis resulted in 12-week sustained virologic response (SVR) rates of 100%. PATIENTS AND METHODS: In TURQUOISE-IV, GT1b-infected patients (n=36) from Russia and Belarus with compensated cirrhosis, who were treatment naive or previously treated with pegylated interferon/ribavirin (RBV), received OBV/PTV/ritonavir+DSV+RBV for 12 weeks. The primary efficacy end point was SVR at 12 weeks. Safety assessments included adverse event (AE) monitoring and laboratory testing. RESULTS: At baseline, patients had Child-Pugh scores of 5 (92%) or 6 (8%). Overall, 69% were treatment experienced (44% prior null responders, 32% relapsers, and 16% partial responders). All patients achieved SVR at 12 weeks (36/36; 100%). No patient experienced a serious AE or discontinued treatment prematurely. Treatment-emergent AEs possibly related to study drugs occurring in greater than or equal to 10% of patients were asthenia (19%), anemia (14%), cough (14%), and headache (11%); most events were mild in severity. Clinically significant laboratory abnormalities were infrequent. CONCLUSION: In Russian and Belarusian patients with hepatitis C GT1b infection and compensated cirrhosis, 100% achieved SVR at 12 weeks after 12 weeks' treatment with OBV/PTV/ritonavir+DSV+RBV. The treatment was well tolerated.

Peginterferon Lambda-1a/Ribavirin with Daclatasvir or Peginterferon Alfa-2a/Ribavirin with Telaprevir for Chronic Hepatitis C Genotype 1b.

The study objective was to compare the efficacy and safety of peginterferon lambda-1a combined with ribavirin/daclatasvir (Lambda/RBV/DCV), versus peginterferon alfa-2a combined with ribavirin/telaprevir (Alfa/RBV/TVR), in patients chronically infected with hepatitis C virus (HCV), genotype 1b. This was a prospective, randomized, open-label, phase 3 study (NCT01718158) in adults (aged ≥18 years) who were treatment naïve or prior relapsers to peginterferon alfa/ribavirin therapy. The primary endpoint was sustained virologic response at post-treatment follow-up week 12 (SVR12). Patients were randomized in a 2:1 ratio to receive 24 weeks of Lambda/RBV/DCV or response-guided 24 or 48 weeks of Alfa/RBV/TVR. Overall, 440 patients were treated (294 with Lambda/RBV/DCV; 146 with Alfa/RBV/TVR). The proportion of patients achieving SVR12 was 88.8% in the Lambda/RBV/DCV arm and 70.5% in the Alfa/RBV/TVR arm (difference between arms: 18.3%; 95% confidence interval: 9.9-25.7; P < 0.0001). Patients in the Lambda/RBV/DCV group had fewer rash-related adverse events (AEs), cytopenic abnormalities, flu-like symptoms, serious AEs, and discontinuations due to AEs, but more liver abnormalities than those in the Alfa/RBV/TVR group. In conclusion, treatment with Lambda/RBV/DCV led to higher SVR12 rates and a more favorable safety profile than Alfa/RBV/TVR in patients with chronic HCV, genotype 1b infection.