Resistance Associated Substitutions in HCV Genotypes

A resistance-associated substitution (RAS) is defined as any amino acid alteration from the consensus sequence in a location linked to reduced susceptibility of a virus to 1 or more antiviral drugs. A specific RAS may or may not confer a phenotypic loss of susceptibility to other/multiple antiviral agents.

Testing for Resistance-Associated Substitutions (RAS) in Hepatitis C virus infection is important because of the high replication rate and the lack of proofreading activity of viral NS5B polymerase. Within the same host, HCV coexists with a population of marginally distinct viral variants and exhibits an inherent propensity to mutate.

The current standard of treatment for hepatitis C virus infection is direct acting antivirals (DAA). RASs, however, may lessen the efficacy of DAA treatment. Virological failure is often associated with selection of RAS related to the drugs used in the therapeutic regimen.

Because DAA regimen selection and duration may vary by genotype, RAS testing is primarily recommended in specific clinical scenarios where treatment failure risk is higher or to guide retreatment after failure. It is not generally advised for all patients beginning HCV treatment and should not postpone therapy. Furthermore, newer pangenotypic regimens with high barriers to resistance may reduce the need for RAS testing in the future.

It is essential to comprehend regional RAS patterns in order to optimise therapeutic approaches. Based on local genotype and resistance trends, this will assist in creating evidence-based guidelines that clinicians may use to optimise the selection of DAA treatments. Healthcare policymakers can use this information to create treatment guidelines and resistance monitoring plans that are particular to a certain location. Additionally, the created baseline makes it possible to monitor the evolution of resistance patterns in the future.

It is necessary to update resistance-interpretation tools on a regular basis as new information becomes available in the dynamic and changing context of HCV treatment. 

References

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