Naturally Occurring Resistance-Associated Variants of Hepatitis C Virus Protease Inhibitors in Poor Responders to Pegylated Interferon-Ribavirin - Université de Lorraine Accéder directement au contenu
Article Dans Une Revue Journal of Clinical Microbiology Année : 2015

Naturally Occurring Resistance-Associated Variants of Hepatitis C Virus Protease Inhibitors in Poor Responders to Pegylated Interferon-Ribavirin

1 UVHCI - Unit of Virus Host Cell Interactions = Biologie structurale des interactions entre virus et cellule hôte
2 LUBEM - Laboratoire Universitaire de Biodiversité et Ecologie Microbienne
3 Laboratoire de Parasitologie et Mycologiede [CHRU Brest]
4 Département de la recherche clinique et de l'innovation - Unité d'évaluation clinique et médico-économique [CHU Grenoble]
5 TIMC-IMAG - Techniques de l'Ingénierie Médicale et de la Complexité - Informatique, Mathématiques et Applications, Grenoble - UMR 5525
6 Biologie cellulaire des infections virales – Cell biology of viral infection
7 Laboratoire de Virologie [HCL-Hôpital de la Croix Rousse]
8 Service de Virologie [Villejuif]
9 UP11 UFR Médecine - Université Paris-Sud - Paris 11 - Faculté de médecine
10 Laboratoire de Virologie [CHU Nantes]
11 ALPHABIO - Laboratoire de biologie médicale
12 Laboratoire de virologie [CHU Angers]
13 Laboratoire Virologie [CHU Toulouse]
14 Hôpital Beaujon [AP-HP]
15 Laboratoire de virologie [Rouen]
16 Service de bactériologie-Virologie-Hygiène [Avicenne]
17 Service de Bactériologie, Virologie, Hygiène [CHU Limoges]
18 CHU Pitié-Salpêtrière [AP-HP]
19 Service de Bactériologie-Virologie-Hygiène [Tours]
20 Centre national de référence du VIH INSERM U966
21 Laboratoire de Virologie
22 CHU Saint-Antoine [AP-HP]
23 Laboratoire de Virologie [Rennes] = Virology [Rennes]
24 Service de Virologie [CHRU Nancy]
25 SIMPA - Stress, Immunité, Pathogènes
26 Service de virologie et d'immunologie biologique
27 Centre National de Référence Virus des hépatites B, C et Delta
28 Laboratoire de bactériologie - hygiène [CHU Amiens]
29 Laboratoire de virologie
Vincent Thibault

Résumé

The pretherapeutic presence of protease inhibitor (PI) resistance-associated variants (RAVs) has not been shown to be predictive of triple-therapy outcomes in treatment-naive patients. However, they may influence the outcome in patients with less effective pegylated interferon (pegIFN)-ribavirin (RBV) backbones. Using hepatitis C virus (HCV) population sequence analysis, we retrospectively investigated the prevalence of baseline nonstructural 3 (NS3) RAVs in a multicenter cohort of poor IFN-RBV responders (i.e., prior null responders or patients with a viral load decrease of <1 log IU/ml during the pegIFN-RBV lead-in phase). The impact of the presence of these RAVs on the outcome of triple therapy was studied. Among 282 patients, the prevalances (95% confidence intervals) of baseline RAVs ranged from 5.7% (3.3% to 9.0%) to 22.0% (17.3% to 27.3%), depending to the algorithm used. Among mutations conferring a >3-fold shift in 50% inhibitory concentration (IC50) for telaprevir or boceprevir, T54S was the most frequently detected mutation (3.9%), followed by A156T, R155K (0.7%), V36M, and V55A (0.35%). Mutations were more frequently found in patients infected with genotype 1a (7.5 to 23.6%) than 1b (3.3 to 19.8%) (P = 0.03). No other sociodemographic or viroclinical characteristic was significantly associated with a higher prevalence of RAVs. No obvious effect of baseline RAVs on viral load was observed. In this cohort of poor responders to IFN-RBV, no link was found with a sustained virological response to triple therapy, regardless of the algorithm used for the detection of mutations. Based on a cross-study comparison, baseline RAVs are not more frequent in poor IFN-RBV responders than in treatment-naive patients and, even in these difficult-to-treat patients, this study demonstrates no impact on treatment outcome, arguing against resistance analysis prior to treatment.

Dates et versions

hal-02014295 , version 1 (11-02-2019)

Identifiants

Citer

Sylvie Larrat, Sophie Vallet, Sandra David-Tchouda, Alban Caporossi, Jennifer Margier, et al.. Naturally Occurring Resistance-Associated Variants of Hepatitis C Virus Protease Inhibitors in Poor Responders to Pegylated Interferon-Ribavirin. Journal of Clinical Microbiology, 2015, 53 (7), pp.2195-2202. ⟨10.1128/JCM.03633-14⟩. ⟨hal-02014295⟩
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