Vol.:(0123456789) 1 3 Archives of Virology https://doi.org/10.1007/s00705-018-3920-9 ORIGINAL ARTICLE Prevalence of naturally occurring amino acid substitutions associated with resistance to hepatitis C virus NS3/NS4A protease inhibitors in São Paulo state Regina Célia Moreira 1  · Ana Paula de Torres Santos 1,2  · Gaspar Lisboa‑Neto 3  · Maria Cássia Jacintho Mendes‑Corrêa 3  · Marcilio Figueiredo Lemos 1  · Fernanda Mello Malta 4  · Rúbia Anita Ferraz Santana 5  · Gregório Tadeu Fernando Dastoli 5  · Vanessa Fusco Duarte de Castro 5  · João Renato Rebello Pinho 4,5 Received: 20 December 2017 / Accepted: 12 April 2018 © Springer-Verlag GmbH Austria, part of Springer Nature 2018 Abstract Hepatitis C (HCV)-infected patients are treated with direct-acting antiviral agents (DAAs) in highly efective, well-tolerated, all-oral regimens. However, naturally occurring resistance-associated amino acid substitutions (RASs) may be selected during treatment. This study aimed to screen naturally occurring RASs NS3/NS4A inhibitors (PIs). Samples were obtained from DAA naïve patients, living in São Paulo state, Brazil. Screening for RASs in the HCV NS3 region was conducted in 859 samples from HCV-infected patients, of which 425 and 434 samples were subtype 1a and 1b, respectively. HCV-RNA was extracted, amplifed, and sequenced. The overall prevalence of RASs to HCV PIs was 9.4%. The following RASs were observed in HCV-1a subtype infected patients: V36L (2.6%), T54S (1.6%), V55I/A (1.2% / 8.9%, respectively), Q80K (2.1%), R155K (0.5%), and D168E (0.2%); and in HCV-1b infected patients: V36L (0.7%), T54A/S (0.2% and 0.5%, respectively), V55A (0.5%), Q80K (0.2%), D168E (1.6%), and M175L (0.5%). HCV 1a infected subjects had higher serum viral load than that seen in patients infected with HCV 1b. There was no diference between the proportions of NS3 RASs with regards to geographic distribution within the investigated areas. These fndings should be supported by additional studies in Brazil to help in the formation of local clinical guidelines for managing hepatitis C. Introduction Globally, infection with Hepatitis C virus (HCV) causes acute and chronic liver disease and may lead to cirrhosis, liver failure, and/or hepatocellular carcinoma. Chronic HCV liver disease is one of the main causes of liver transplan- tation in developed countries. The global prevalence of HCV infection is estimated to be 1%, with about 80 million chronically infected individuals worldwide [1]. In Brazil, the prevalence of HCV antibodies is estimated to be 0.8%, corresponding to 1.4 to 1.6 million infected subjects [2]. Until 2011 the only available treatment was based on the combination of pegylated interferon alpha (peg-IFNα) and ribavirin (RBV). These drugs – particularly interferon - did not have direct antiviral activity but was used for HCV treat- ment based on its immunomodulatory efects on viral rep- lication. Moreover, a sustained virological response (SVR) was limited to about 50% of patients infected with HCV genotype 1, frequently demanding longer periods of treat- ment, and almost always permeated by adverse events [3]. Communicated by Michael Carpenter. * Regina Célia Moreira regina.moreira7@gmail.com 1 Laboratory of Viral Hepatitis, Virology Center, Instituto Adolfo Lutz, Avenida Dr. Arnaldo, 355, Cerqueira César, São Paulo, SP CEP 01246-902, Brazil 2 Divisão de Laboratório Central, Laboratório de Imunologia, Faculdade de Medicina, Hospital das Clínicas, Universidade de São Paulo, São Paulo, SP, Brazil 3 Department of Infectious Diseases, School of Medicine, University of São Paulo, São Paulo, SP, Brazil 4 Laboratory of Tropical Gastroenterology and Hepatology “João de Queiroz and Castorina Bettencourt Alves”-LIM 07-Institute of Tropical Medicine Department of Gastroenterology, School of Medicine, University of São Paulo, São Paulo, SP, Brazil 5 Albert Einstein Medicina Diagnóstica, Hospital Israelita Albert Einstein, São Paulo, SP, Brazil