Hepatitis C virus genotype 4 resistance and subtype demographic characterization of patients treated with ombitasvir plus paritaprevir/ritonavir.
Hepatitis C virus (HCV) genotype 4 (GT4) is genetically diverse, with 17 confirmed subtypes, and comprises approximately 13% of infections worldwide. In this study, we identified GT4 subtypes by phylogenetic analysis, assessed differences in patient demographics across GT4 subtypes, examined baseline sequence variability among subtypes and the potential impact on treatment outcome, and analyzed the development of viral resistance in patients who received a regimen of ombitasvir (nonstructural protein 5A [NS5A] inhibitor) plus ritonavir-boosted paritaprevir (NS3/4A inhibitor) with or without ribavirin (RBV) for the treatment of HCV GT4 infection. Phylogenetic analysis of HCV NS3/4A, NS5A, and NS5B nucleotide sequences identified 7 subtypes (4a, 4b, 4c, 4d, 4f, 4g/4k, and 4o) among 132 patient samples. Subtype prevalence varied by country, and the distributions of patient birth cohort and race were significantly different across GT4 subtypes 4a, 4d, and non-4a/4d. Baseline amino acid variability was detected in NS5A across GT4 subtypes but had no impact on treatment outcome. Three patients experienced virologic failure and were infected with subtype 4d, and the predominant resistance-associated variants at the time of failure were D168V in NS3 and L28V in NS5A. Overall, high response rates were observed among patients infected with 7 HCV GT4 subtypes, with no impact of baseline variants on treatment outcome. GT4 subtype distribution in this study differed based on patient demographics and geography.
Research & Development, AbbVie, Inc., North Chicago, Illinois, USA gretja.schnell@abbvie.com.
Gretja
G
Schnell
Research & Development, AbbVie, Inc., North Chicago, Illinois, USA.
Rakesh
R
Tripathi
Research & Development, AbbVie, Inc., North Chicago, Illinois, USA.
Jill
J
Beyer
Research & Development, AbbVie, Inc., North Chicago, Illinois, USA.
Thomas
T
Reisch
Research & Development, AbbVie, Inc., North Chicago, Illinois, USA.
Preethi
P
Krishnan
Research & Development, AbbVie, Inc., North Chicago, Illinois, USA.
Liangjun
L
Lu
Research & Development, AbbVie, Inc., North Chicago, Illinois, USA.
Tatyana
T
Dekhtyar
Research & Development, AbbVie, Inc., North Chicago, Illinois, USA.
Coleen
C
Hall
Research & Development, AbbVie, Inc., North Chicago, Illinois, USA.
Regis A
RA
Vilchez
Research & Development, AbbVie, Inc., North Chicago, Illinois, USA.
Tami
T
Pilot-Matias
Research & Development, AbbVie, Inc., North Chicago, Illinois, USA.
Christine
C
Collins
D000328:Adult; D000813:Anilides / Q000627:therapeutic use*; D000998:Antiviral Agents / Q000627:therapeutic use*; D002219:Carbamates / Q000627:therapeutic use*; D003521:Cyclopropanes; D024882:Drug Resistance, Viral / Q000235:genetics; D004359:Drug Therapy, Combination; D005260:Female; D005838:Genotype; D016174:Hepacivirus / Q000145:classification / Q000187:drug effects* / Q000235:genetics* / Q000472:pathogenicity; D019698:Hepatitis C, Chronic / Q000188:drug therapy / Q000821:virology; D006801:Humans; D047029:Lactams, Macrocyclic; D047028:Macrocyclic Compounds / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D010802:Phylogeny; D011392:Proline / Q000031:analogs & derivatives; D019438:Ritonavir / Q000627:therapeutic use*; D013449:Sulfonamides; D016896:Treatment Outcome; D014633:Valine; D055815:Young Adult
D000813:Anilides; D000998:Antiviral Agents; D002219:Carbamates; D003521:Cyclopropanes; D047029:Lactams, Macrocyclic; D047028:Macrocyclic Compounds; D013449:Sulfonamides; C586094:ombitasvir; D011392:Proline; D014633:Valine; D019438:Ritonavir; C585405:paritaprevir