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

Sylvie Larrat 1 Sophie Vallet 2 Sandra David-Tchouda 3 Alban Caporossi Jennifer Margier Christophe Ramière Caroline Scholtes Stéphanie Haïm-Boukobza Anne-Marie Roque-Afonso 4 Bernard Besse 5 Elisabeth André-Garnier 6 Sofiane Mohamed 7 Philippe Halfon 7 Adeline Pivert 8 Hélène Leguillou-Guillemette Florence Abravanel 9 Matthieu Guivarch Vincent Mackiewicz Olivier Lada 10, 11, 12 Thomas Mourez 13 Jean-Christophe Plantier 14 Yazid Baazia 15 Sophie Alain 16 Sebastien Hantz 17 Vincent Thibault 18 Catherine Gaudy-Graffin 19 Dorine Bouvet 20 Audrey Mirand Cécile Henquell 21 Joel Gozlan Gisèle Lagathu 22 Charlotte Pronier Aurélie Velay Evelyne Schvoerer 23 Pascale Trimoulet 24 Hervé Fleury 25, 26 Magali Bouvier-Alias Etienne Brochot 27, 28 Gilles Duverlie 28 Sarah Maylin Stéphanie Gouriou 2 Jean-Michel Pawlotsky 29 Patrice Morand 1
Abstract : 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.
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Journal of Clinical Microbiology, American Society for Microbiology, 2015, 53 (7), pp.2195-202
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Dernière modification le : lundi 29 octobre 2018 - 23:06:45

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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, American Society for Microbiology, 2015, 53 (7), pp.2195-202. 〈hal-01243613〉

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