de Torres Santos Ana Paula, Martins Silva Vanessa Cristina, Mendes-Corrêa Maria Cássia, Lemos Marcilio Figueiredo, de Mello Malta Fernanda, Santana Rúbia Anita Ferraz, Dastoli Gregório Tadeu Fernando, de Castro Vanessa Fusco Duarte, Pinho João Renato Rebello, Moreira Regina Célia
Laboratory of Viral Hepatitis, Virology Center, Instituto Adolfo Lutz, São Paulo, SP, Brazil.
Divisão de Laboratório Central, Laboratório de Imunologia, Faculdade de Medicina, Hospital das Clínicas, Universidade de São Paulo, São Paulo, SP, Brazil.
Infect Drug Resist. 2021 Feb 24;14:723-730. doi: 10.2147/IDR.S247071. eCollection 2021.
Globally, it is estimated that 71 million people are chronically infected with hepatitis C, and 10-20% of these will develop cirrhosis and hepatocellular carcinoma. The development of new direct-acting antiviral (DAA) drugs has contributed to sustained virological response (SVR), eliminating the infection and achieving cure of chronic hepatitis C. However, treated patients can develop HCV resistance to DAAs, which can contribute to the failure of treatment. Here, we aimed to evaluate the prevalence and specific pattern of NS5A and NS5B resistance-associated substitutions (RAS) in samples from patients chronically infected with HCV genotype 3a at a public health laboratory, Instituto Adolfo Lutz, São Paulo, Brazil.
Serum samples from the enrolled individuals were submitted to "in-house" polymerase chain reaction amplification of NS5A and NS5B non-structural protein genes, which were then sequenced by Sanger method.
A total of 170 and 190 samples were amplified and analyzed for NS5A and NS5B, respectively. For NS5A, 20 (12.0%) samples showed some important RAS; 16 (9.0%) showed some type of substitution and 134 (79.0%) showed no polymorphism. No sample showed any RAS for NS5B.
This study found important RAS in samples from naïve chronic HCV patients in some areas from São Paulo. The most prevalent were A62S, A30K, and Y93H, which could indicate an increase in resistance to some DAAs used in HCV treatment.
据全球估计，有7100万人慢性感染丙型肝炎，其中10%-20%的人会发展为肝硬化和肝细胞癌。新型直接抗病毒（DAA）药物的研发有助于实现持续病毒学应答（SVR），消除感染并治愈慢性丙型肝炎。然而，接受治疗的患者可能会对DAA产生丙型肝炎病毒（HCV）耐药性，这可能导致治疗失败。在此，我们旨在评估巴西圣保罗阿道夫·卢茨研究所这一公共卫生实验室中慢性感染HCV 3a基因型患者样本中NS5A和NS5B耐药相关替代（RAS）的流行情况和特定模式。
将入组个体的血清样本进行NS5A和NS5B非结构蛋白基因的“内部”聚合酶链反应扩增，然后采用桑格法进行测序。
分别对170份和190份样本进行了NS5A和NS5B的扩增及分析。对于NS5A，20份（12.0%）样本显示出一些重要的RAS；16份（9.0%）显示出某种类型的替代，134份（79.0%）未显示多态性。没有样本显示NS5B有任何RAS。
本研究在圣保罗部分地区初治慢性HCV患者的样本中发现了重要的RAS。最常见的是A62S、A30K和Y93H，这可能表明对HCV治疗中使用的某些DAA的耐药性增加。
