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Title: Prevalence of resistance-associated substitutions to direct-acting antiviral agents in hemodialysis and renal transplant patients infected with hepatitis C virus
Authors: TAVARES, Rita Chelly FelixFELDNER, Ana Cristina de Castro AmaralPINHO, Joao Renato RebelloMALTA, Fernanda de MelloCARVALHO-FILHO, Roberto JoseSANTANA, Rtibia Anita FerrazCASTRO, Vanessa Fusco Duarte deDASTOLI, Gregorio Tadeu FernandoLIMA, Juliana CustadioFERRA, Maria Lucia Cardoso Gomes
Citation: INFECTION AND DRUG RESISTANCE, v.11, p.1993-2000, 2018
Abstract: Background: Direct-acting antiviral agents (DAAs) permit the use of interferon (IFN)-free regimens to treat hepatitis C (HCV) in patients with chronic kidney disease (CKD) on hemodialysis (HD) or renal transplant (RTx) recipients, with excellent response rates and safety. However, the occurrence of basal or therapy-induced resistance-associated substitutions (RASs) to DAAs can result in treatment failure. The aim of this study was to estimate the prevalence of RASs to NS3A, NS5A and NS5B inhibitors, and particularly the Q80K polymorphism, in CKD patients on HD and RTx recipients infected with HCV. Patients and methods: HD and RTx patients infected with HCV-genotype 1 (GT1) were subjected to sequencing of the NS3, NS5A and NS5B regions. Results: Direct sequencing of NS3 protease, NS5A and NS5B was performed in 76 patients (HD, n=37; RTx, n=39). The overall prevalence of RASs was 38.2%, but only 5.3% of the patients had mutations in more than one region. Substitutions were detected in NS3A (17.8%), NS5A (21.9%) and NS5B (8.4%). Q80K was detected in 1.5 % of the patients. Highly inhibitory RASs were uncommon (L31M, 2.6%; L159F+C316N, 2.6%). RASs were more prevalent in HCV-GT1a (42.9%) than in HCV-GT1b (32.4%), P=0.35. RASs were detected in 52.4% of treatment-naive patients and 27.8% of peg-IFN/ribavirin-experienced patients (P=0.12). The presence of RASs was associated with time of RTx (P=0.01). Conclusion: The Q80K polymorphism was uncommon in our sample of HD and RTx patients. Despite the high prevalence of naturally occurring RASs, most of the substitutions detected were associated with a low level of resistance to DAAs.
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Artigos e Materiais de Revistas Científicas - LIM/03
Artigos e Materiais de Revistas Científicas - LIM/07

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