BACKGROUND: In HCV-infected people who fail to achieve sustained virological response after receiving a direct-acting antiviral regimen, virological failure is almost always accompanied by the presence of resistance-associated substitutions (RASs) in the target protein(s). The aim of this long-term observational study was to evaluate the persistence of NS3/4A and NS5A RASs in participants with genotype (GT) 1 infection who relapsed following treatment with a grazoprevir-containing treatment regimen. METHODS: RASs were evaluated at baseline (that is, pre-dose on day 1 of the original treatment), at the time of virological failure, and up to follow-up week 96. A total of 58 participants were included. RESULTS: In participants treated with elbasvir/grazoprevir ± ribavirin, observed baseline NS3 RASs included 56F, 80K/L, 122N and 170V/I, and observed treatment-emergent NS3 RASs included 36M, 56F/H, 122G, 132I, 156G/I/L/P/T, 168A/E/G/V/Y and 170T. Observed baseline NS5A RASs included 28M/T/V, 30H/R, 31M/V and 93H/N, and treatment-emergent NS5A RASs included 28A/G/S/T, 30H/R, 31M/V and 93H/N/S. Baseline NS3 and NS5A RASs present at time of failure tended to persist during follow-up, and most were detectable for more than 2 years following virological failure. Treatment-emergent NS5A RASs present at time of failure also tended to persist for more than 2 years following virological failure (93%). By contrast, >80% of treatment-emergent NS3 RASs detected at failure had been supplanted by wild type by week 36. CONCLUSIONS: Treatment-emergent NS5A RASs can persist for extended periods of time. Retreatment strategies should take account of the presence of these RASs.
BACKGROUND: In HCV-infected people who fail to achieve sustained virological response after receiving a direct-acting antiviral regimen, virological failure is almost always accompanied by the presence of resistance-associated substitutions (RASs) in the target protein(s). The aim of this long-term observational study was to evaluate the persistence of NS3/4A and NS5A RASs in participants with genotype (GT) 1 infection who relapsed following treatment with a grazoprevir-containing treatment regimen. METHODS: RASs were evaluated at baseline (that is, pre-dose on day 1 of the original treatment), at the time of virological failure, and up to follow-up week 96. A total of 58 participants were included. RESULTS: In participants treated with elbasvir/grazoprevir ± ribavirin, observed baseline NS3 RASs included 56F, 80K/L, 122N and 170V/I, and observed treatment-emergent NS3 RASs included 36M, 56F/H, 122G, 132I, 156G/I/L/P/T, 168A/E/G/V/Y and 170T. Observed baseline NS5A RASs included 28M/T/V, 30H/R, 31M/V and 93H/N, and treatment-emergent NS5A RASs included 28A/G/S/T, 30H/R, 31M/V and 93H/N/S. Baseline NS3 and NS5A RASs present at time of failure tended to persist during follow-up, and most were detectable for more than 2 years following virological failure. Treatment-emergent NS5A RASs present at time of failure also tended to persist for more than 2 years following virological failure (93%). By contrast, >80% of treatment-emergent NS3 RASs detected at failure had been supplanted by wild type by week 36. CONCLUSIONS: Treatment-emergent NS5A RASs can persist for extended periods of time. Retreatment strategies should take account of the presence of these RASs.
Authors: Ernest Asante-Appiah; Paul Ingravallo; Patricia McMonagle; Karin Bystol; Ellen Xia; Stephanie Curry; Ping Qiu; Stuart Black; Robert Chase; Rong Liu; Fred Lahser Journal: Antimicrob Agents Chemother Date: 2019-09-16 Impact factor: 5.191
Authors: Ernest Asante-Appiah; Rong Liu; Stephanie Curry; Patricia McMonagle; Sony Agrawal; Donna Carr; Laura Rokosz; Frederick Lahser; Karin Bystol; Robert Chase; Stuart Black; Eric Ferrari; Paul Ingravallo; Ling Tong; Wensheng Yu; Joseph Kozlowski Journal: Antimicrob Agents Chemother Date: 2018-10-24 Impact factor: 5.191
Authors: Karen K Kyuregyan; Vera S Kichatova; Anastasiya A Karlsen; Olga V Isaeva; Sergei A Solonin; Stefan Petkov; Morten Nielsen; Maria G Isaguliants; Mikhail I Mikhailov Journal: Biomedicines Date: 2020-04-07
Authors: Vanessa D Costa; Patricia Pellegrini; Vivian Rotman; Ana Maria Pittella; Estevão P Nunes; Barbara V Lago; Elisabeth Lampe; Francisco C A Mello Journal: Viruses Date: 2019-10-31 Impact factor: 5.048