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

• A 0.5% detection threshold allows for a better characterization of the HCV viral population.
• UDPS demonstrated that the frequency of BOC or TLP RAVs persist for at least one year after therapeutic cessation.
• The relative mutant viral load must be considered prior to any PIs based re-treatment.

BackgroundThe 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.ObjectivesTo 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 designThe 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).ResultsBaseline 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 1a patients (18%). Persistence mutations were found only in HCV GT 1a 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.ConclusionThe UDPS follow-up analysis demonstrated that the presence of BOC or TLP-RAVs persist one year after therapy cessation only in HCV GT 1a 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.