After treatment failure on sofosbuvir plus an NS5A inhibitor, treatment options are limited. A randomized trial of the safety and efficacy of 12 and 16 weeks of glecaprevir and pibrentasvir (G/P), was evaluated, performing a randomized trial in patients with genotype 1 infection. A phase 3B, open-label study of those who received previous treatment with sofosbuvir plus an NS5A inhibitor was carried out. Patients without cirrhosis were randomly assigned to groups that received G/P for 12 weeks or 16 weeks (78 group A, 49 group B). Patients with compensated cirrhosis were randomly assigned to groups that received G/P and ribavirin for 12 weeks or G/P for 16 weeks. The primary endpoint was an SVR 12 weeks after treatment.
Samples collected at baseline and at time of treatment failure were sequenced for resistantassociated substitutions in NS3 and NS5A. In the 171 patients, 81% were men, 79% had HCV genotype 1A infection and 44% were black. Proportion of patients with SVR 12 weeks after treatment in group A, B, C and D were 90%, 94%, 86% and 97%, respectively. The treatment failed in 13 (7.3%) of patients with HCV genotype 1A infection, 6 (7.9%) in group A, 3 (6.1%) in group B, 3 (6.1%) in group C, and 1 in group B.
Most patients had baseline resistanceassociated substitutions in NS5A treatment. Emerged resistance-associated substitutions in NS3 and NS5A were observed in 9 and 10 patients for treatment failure, respectively. G/P was well tolerated. Ribavirin increased adverse events, but did not increase efficacy.
It was concluded in a randomized study of patients with chronic HCV genotype 1 infection who received previous treatment with sofosbuvir plus an NS5A inhibitor, 16 weeks treatment with G/P produces same, but produced SVR 12 weeks after treatment with greater than 90% of patients, including those with compensated cirrhosis.