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Prevalence of naturally occurring protease inhibitor resistance-associated variants in hemodialysis and renal transplant patients with hepatitis C virus infection.
Tavares, Rita C F; Feldner, Ana C C A; Pinho, João R R; Uehara, Silvia N O; Emori, Christini T; Carvalho-Filho, Roberto J; Silva, Ivonete S S; Santana, Rúbia A F; de Castro, Vanessa F D; Castoli, Gregório T F; Cristovão, Charliana U; Ferraz, Maria L C G.
Affiliation
  • Tavares RCF; aGastroenterology Division, Federal University of Sao Paulo bAlbert Einstein Medicina Diagnóstica, Hospital Israelita Albert Einstein cDepartment of Gastroenterology, School of Medicine, Laboratory of Tropical Gastroenterology and Hepatology 'João Alves de Queiroz and Castorina Bittencourt Alves', LIM-07, Institute of Tropical Medicine, University of São Paulo, São Paulo, Brazil.
Eur J Gastroenterol Hepatol ; 29(7): 754-758, 2017 Jul.
Article in En | MEDLINE | ID: mdl-28234637
ABSTRACT
Background NS3 protease inhibitors (PIs) were the first direct antiviral agents used for the treatment of hepatitis C virus. The combination of second-wave PIs with other direct antiviral agents enabled the use of interferon-free regimens for chronic kidney disease patients on dialysis and renal transplant (RTx) recipients, populations in which the use of interferon and ribavirin is limited. However, the occurrence of PI resistance-associated variants (RAVs), both baseline and induced by therapy, has resulted in the failure of many treatment strategies. Methods The aim of this study was to estimate the prevalence of PI RAVs and of the Q80K polymorphism in chronic kidney disease patients on hemodialysis and RTx recipients. Direct sequencing of the NS3 protease was performed in 67 patients (32 hemodialysis and 35 RTx).Results RAVs to PIs were detected in 18% of the patients V55A (9%), V36L (1.5%), T54S (1.5%), S122N (1.5%), I170L (1.5%), and M175L (1.5%). Only 1.5% of the patients carried the Q80K polymorphism. The frequency of these mutations was more than two times higher in patients infected with GT1a (25%) than GT1b (9.7%) (P=0.1). The mutations were detected in 20% of treatment-naive patients and in 15.6% of peginterferon/ribavirin-experienced patients (P=0.64). Furthermore, no mutation that would confer high resistance to PIs was detected.Conclusion The Q80K polymorphism was rare in the population studied. The occurrence of RAVs was common, with predominance in GT1a. However, the variants observed were those associated with a low level of resistance to PIs, facilitating the use of these drugs in this special group of patients.
Subject(s)

Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Antiviral Agents / Polymorphism, Genetic / Protease Inhibitors / Renal Dialysis / Kidney Transplantation / Hepatitis C / Viral Nonstructural Proteins / Hepacivirus / Drug Resistance, Viral / Renal Insufficiency, Chronic Type of study: Diagnostic_studies / Prevalence_studies Limits: Adolescent / Adult / Aged / Female / Humans / Male / Middle aged Country/Region as subject: America do sul / Brasil Language: En Journal: Eur J Gastroenterol Hepatol Journal subject: GASTROENTEROLOGIA Year: 2017 Document type: Article Affiliation country: Brazil

Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Antiviral Agents / Polymorphism, Genetic / Protease Inhibitors / Renal Dialysis / Kidney Transplantation / Hepatitis C / Viral Nonstructural Proteins / Hepacivirus / Drug Resistance, Viral / Renal Insufficiency, Chronic Type of study: Diagnostic_studies / Prevalence_studies Limits: Adolescent / Adult / Aged / Female / Humans / Male / Middle aged Country/Region as subject: America do sul / Brasil Language: En Journal: Eur J Gastroenterol Hepatol Journal subject: GASTROENTEROLOGIA Year: 2017 Document type: Article Affiliation country: Brazil