A Boceprevir Failure in a Patient Infected with HCV Genotype 1G: Importance and Limitations of Virus Genotyping Prior to HCV Protease-Inhibitor-Based Therapy

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Abstract
A patient classified as HCV-1a-positive by both LiPA Siemens 2.0 and Abbott RealTime HCV Genotype II was instead found to be infected with HCV-1g, as determined by phylogenetic analysis of NS3 sequences. HCV-1g NS3 sequences available to date naturally harbour the resistance substitution T54S, plus P131S and L135F changes, located in the highly conserved NS3 positions within the boceprevir-binding site, as determined by structural modelling. HCV-1g NS3 sequences show some similarities to HCV-4 and are poorly responsive to interferon/ribavirin and to boceprevir/telaprevir; this patient was also a null-responder to boceprevir treatment. Baseline genotypic resistance testing may provide crucial information for the management of first-generation protease-inhibitor-based regimens, including both HCV genotype/subtype and natural resistance.

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