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Analysis by population- and deep-sequencing of polymorphisms with excessive resistance to NS5A inhibitors in treatment-naive subjects with HCV genotype 1a and 3a
Future interferon-free combo DAA treatments could include HCV NS5A inhibitors for potent pan-genotypic effect. We have with both population and deep-sequencing method studied NS5A resistance associated polymorphisms at baseline in treatment-naive patient samples of HCV genotypes (GTs) 1a and 3a, the most common GTs in Sweden. Sera from 55 patients with GT1a and 35 patients with GT3a were collected for the NS5A analysis. With the population-sequencing method the NS5A genes were amplified by nested PCR method with degenerated primers to enable a broad genotype analysis. It should be of importance to detect low levels of NS5A resistant associated polymorphisms, as such can display resistance as high as 50,000 fold. Our preliminary data suggest that further evaluation is needed to study the role of baseline NS5A resistance in GT1a and 3a subjects for future interferon-free combo DAA treatments.