Clinical relevance of the HCV protease inhibitor-resistant mutant viral load assessed by ultra-deep pyrosequencing in treatment failure

Background: The detection of low frequency mutants in patients with hepatitis C virus (HCV) receiving direct-acting antivirals (DAAs) is still debated. The clinical relevance of the mutant viral load has not yet been evaluated. Objectives: To assess the viral load of resistance associated variants (RAVs) in patients at different time points, including the baseline, virological failure and one year after the cessation of therapy. Study design: The study included 22 patients who were previously treated with protease inhibitors (PI) (with telaprevir and boceprevir). For each patient, three time points were assessed using ultra-deep pyrosequencing (UDPS). Results: Baseline mutations were observed in 14/22 patients (64%). At virological failure, RAVs were detected in 18/22 patients (82%). Persistent RAVs were observed in four HCV GT la patients (18%). Persistence mutations were found only in HCV GT la patients. The baseline relative V36M, R155K, R155T and A156T mutation load of patients with persistent RAVs was significantly higher (P < 0.001) than those of patients without persistent RAVs. Conclusion: The UDPS follow-up analysis demonstrated that the presence of BOC or TLP-RAVs persist one year after therapy cessation only in HCV GT la patients. The relative mutant viral load should be considered prior to any PI based re-treatment. This concept of the baseline mutation viral load must be validated using current therapy and must be validated on a larger cohort. (C) 2016 Elsevier B.V. All rights reserved.