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J Clin Virol. 2016 May;78:36-43. doi: 10.1016/j.jcv.2016.02.022. Epub 2016 Feb 26.

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

Author information

1
Laboratoire Alphabio, Marseille, France; CRCM, Immunity and Cancer, Inserm, U1068; Institut Paoli-Calmettes; Aix-Marseille Université, UM 105; CNRS, UMR7258, F-13009 Marseille, France.
2
Département d'hépato-gastroenterologie, Hôpital Saint Joseph, Marseille, France.
3
Laboratoire Alphabio, Marseille, France.
4
Hôpital Européen, Marseille, France.
5
Advanced Biological Laboratories (ABL), Luxembourg, Luxembourg.
6
CRCM, Immunity and Cancer, Inserm, U1068; Institut Paoli-Calmettes; Aix-Marseille Université, UM 105; CNRS, UMR7258, F-13009 Marseille, France.
7
Laboratoire Alphabio, Marseille, France; Hôpital Européen, Marseille, France. Electronic address: philippe.halfon@alphabio.fr.

Abstract

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 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.

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 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.

KEYWORDS:

HCV; Mutant viral load; Protease inhibitors; Ultra-deep pyrosequencing

PMID:
26971166
DOI:
10.1016/j.jcv.2016.02.022
[Indexed for MEDLINE]

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