Detection of a Genetic Footprint of the Sofosbuvir Resistance-Associated Substitution S282T After HCV Treatment Failure

摘要: The major resistance-associated substitution for sofosbuvir (S282T) in HCV NS5B causes severe viral fitness costs and rapidly reverts back to prototype the absence of selection pressure. Accordingly, resistance against is rarely detected even patients after treatment failure. We report a case GT3a infected patient with breakthrough under SOF/DCV therapy. At time RAS S282T was predominant then disappeared during follow-up by week 12 treatment. Interestingly, despite only serine encoded position 282 follow-up, two distinct genetic pathways reversion were detectable. In 31% quasispecies original codon present whereas majority an alternative selected. This usage unique all isolates from database remained detectable as footprint prior at RNA level least 6 months. Comparative analyses sequences before DAA may help elucidate patient’s history selection, which particularly valuable highly unfit substitutions that are short period time. If such changes increase risk re-selection upon second exposure SOF remains be addressed.