HCV HCV genotype 4, 5 and 6: Distribution of viral subtypes and sustained virologic response rates in clinical trials of approved direct‐acting antiviral regimens

摘要

Summary Multiple direct‐acting antiviral ( DAA )‐based regimens are now available for all hepatitis C virus ( HCV ) genotypes ( GT s). Because HCV GT 4, 5 and 6 are less common in the United States ( US ) and worldwide, relatively small numbers of participants with these GT s were evaluated in individual clinical trials. To provide a comprehensive description of subtype diversity and treatment outcomes in clinical trials for these less common GT s, we analysed data from 744 participants with HCV GT 4 (n?=?573), GT 5 (n?=?81), or GT 6 (n?=?90) across 18 clinical trials of DAA regimens.?These data are from US New Drug Applications submitted between 2014 and 2017, and our analyses included only approved regimens. Excluding unresolved or mixed subtypes, the distribution of reported GT 4 subtypes was 49% 4a, 31% 4d and 16% for one of 14 other subtypes. The distribution of GT 6 subtypes was 39% 6a, 27% 6e, 8% 6?L and 23% for one of 11 other subtypes. Across approved regimens, sustained virologic response rates 12?weeks post‐treatment ( SVR 12) for GT 4, 5 and 6 ranged from 91% to 100%, 93% to 97% and 96% to 100%, respectively. SVR 12 by GT 4 subtype ranged from 96% to 100% for 4a and 81% to 100% for 4d. Virologic failures occurred in GT 4a, 4b, 4d and 4r. For GT 6, SVR 12 was 100% for all subtypes except 6?L, for which 1 of 7 participants experienced virologic failure. To our knowledge, this is the largest compilation of HCV GT 4, 5 or 6 clinical trial data. These analyses may be useful for clinicians treating HCV GT 4, 5 or 6.