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Characterization of demographics and NS 5A genetic diversity for hepatitis C virus genotype 4‐infected patients with or without cirrhosis treated with ombitasvir/paritaprevir/ritonavir
Author(s) -
Schnell G.,
Tripathi R.,
Beyer J.,
Reisch T.,
Krishnan P.,
Dekhtyar T.,
Irvin M.,
Hall C.,
Yu Y.,
Mobashery N.,
Redman R.,
PilotMatias T.,
Collins C.
Publication year - 2018
Publication title -
journal of viral hepatitis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.329
H-Index - 100
eISSN - 1365-2893
pISSN - 1352-0504
DOI - 10.1111/jvh.12906
Subject(s) - ombitasvir , ritonavir , paritaprevir , genotype , virology , medicine , hepatitis c virus , biology , virus , genetics , ribavirin , viral load , gene , antiretroviral therapy
Summary Hepatitis C virus ( HCV ) genotype 4 ( GT 4) is genetically diverse with 17 confirmed and 4 provisional subtypes. In this report, HCV GT 4‐infected patient samples from Phase 2/3 clinical studies were analysed to characterize global demographics and genetic diversity of GT 4 infection among patients treated with ombitasvir ( OBV , NS 5A inhibitor) plus paritaprevir/r ( NS 3/4A inhibitor codosed with ritonavir). Among 17 subtypes isolated from GT 4‐infected patients in the PEARL ‐I and AGATE ‐I studies, subtype prevalence by country of enrolment and country of origin suggested that subtypes 4a and 4d were likely circulating in Europe, while heterogeneous GT 4 subtypes and a portion of GT 4a detected in European and North American countries were likely due to immigration of HCV ‐infected patients from Africa. The distributions of birth cohort and race were also significantly different across GT 4 subtypes 4a, 4d, and non‐4a/4d. In addition, phylogenetic analyses of NS 5A sequences revealed clustering within subtype 4a which segregated by the patient‐reported country of origin and the presence of the L30R/S polymorphism. HCV NS 5A sequences derived from GT 4a‐infected patients who originated from Europe and the United States clustered separately from sequences derived from patients who originated from Egypt, suggesting that genetically distinct strains of subtype 4a may be circulating globally. Finally, NS 5A baseline polymorphisms were frequently detected at amino acid positions of interest for the inhibitor‐class and OBV retained activity against 37 of 39 NS 5A GT 4 clinical isolates, with no impact on treatment outcome in the PEARL ‐I and AGATE ‐I studies.