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2015 ; 59
(9
): 5445-54
Nephropedia Template TP
gab.com Text
Twit Text FOAVip
Twit Text #
English Wikipedia
Resistance analysis of baseline and treatment-emergent variants in hepatitis C
virus genotype 1 in the AVIATOR study with paritaprevir-ritonavir, ombitasvir,
and dasabuvir
#MMPMID26100711
Krishnan P
; Tripathi R
; Schnell G
; Reisch T
; Beyer J
; Irvin M
; Xie W
; Larsen L
; Cohen D
; Podsadecki T
; Pilot-Matias T
; Collins C
Antimicrob Agents Chemother
2015[Sep]; 59
(9
): 5445-54
PMID26100711
show ga
AVIATOR, a phase 2 clinical trial, evaluated ritonavir-boosted paritaprevir (a
protease inhibitor), ombitasvir (an NS5A inhibitor), and dasabuvir (a
nonnucleoside polymerase inhibitor) (the three-drug [3D] regimen) with or without
ribavirin (RBV) for 8, 12, or 24 weeks in 406 HCV genotype 1 (GT1)-infected
patients. The rate of sustained virologic response 24 weeks after treatment
ranged from 88% to 100% across the arms of the 3D regimen with or without RBV; 20
GT1a-infected patients and 1 GT1b-infected patient experienced virologic failure
(5.2%). Baseline resistance-conferring variants in NS3 were rare. M28V in GT1a
and Y93H in GT1b were the most prevalent preexisting variants in NS5A, and C316N
in GT1b and S556G in both GT1a and GT1b were the most prevalent variants in NS5B.
Interestingly, all the GT1a sequences encoding M28V in NS5A were from the United
States, while GT1b sequences encoding C316N and S556G in NS5B were predominant in
the European Union. Variants preexisting at baseline had no significant impact on
treatment outcome. The most prevalent treatment-emergent resistance-associated
variants (RAVs) in GT1a were R155K and D168V in NS3, M28T and Q30R in NS5A, and
S556G in NS5B. The single GT1b-infected patient experiencing virologic failure
had no RAVs in any target. A paritaprevir-ritonavir dose of 150/100 mg was more
efficacious in suppressing R155K in NS3 than a 100/100-mg dose. In patients who
failed after receiving 12 or more weeks of treatment, RAVs were selected in all 3
targets, while most patients who relapsed after 8 weeks of treatment did so
without any detectable RAVs. Results from this study guided the selection of the
optimal treatment regimen, treatment duration, and paritaprevir dose for further
development of the 3D regimen. (This study has been registered at
ClinicalTrials.gov under registration number NCT01464827.).