HCV kinetic and modeling analyses indicate similar time to cure among sofosbuvir combination regimens with daclatasvir, simeprevir or ledipasvir

被引:60
作者
Dahari, Harel [1 ,2 ,10 ]
Canini, Laetitia [1 ,3 ]
Graw, Frederik [4 ]
Uprichard, Susan L. [1 ]
Araujo, Evaldo S. A. [5 ]
Penaranda, Guillaume [6 ]
Coquet, Emilie [7 ]
Chiche, Laurent [7 ]
Riso, Aurelie [8 ]
Renou, Christophe [9 ]
Bourliere, Marc [8 ]
Cotler, Scott J. [1 ]
Halfon, Philippe [6 ,7 ]
机构
[1] Loyola Univ, Med Ctr, Div Hepatol, Program Expt & Theoret Modeling, Maywood, IL 60153 USA
[2] Los Alamos Natl Lab, Theoret Biol & Biophys Grp, Los Alamos, NM USA
[3] Univ Edinburgh, Ctr Immun Infect & Evolut, Edinburgh, Midlothian, Scotland
[4] Heidelberg Univ, BioQuant Ctr, Ctr Modeling & Simulat Biosci, Heidelberg, Germany
[5] Univ Sao Paulo, Hosp Clin, Sao Paulo, Brazil
[6] Lab Alphabio, Marseille, France
[7] Hop Europeen, Internal Med & Infect Dis, Marseille, France
[8] Hop St Joseph, Div Hepatol, Marseille, France
[9] CH Hyeres, Div Hepatol, Hyeres, France
[10] Hop Europeen, Lab Alphabio, Internal Med & Infect Dis Dept, F-13003 Marseille, France
基金
英国生物技术与生命科学研究理事会;
关键词
HCV; Viral kinetics; Mathematical modeling; SVR; Duration of therapy; GENOTYPE; 1; INFECTION; HEPATITIS-C; TRANSIENT ELASTOGRAPHY; VIROLOGICAL RESPONSE; TREATMENT-NAIVE; VIRAL KINETICS; OPEN-LABEL; RIBAVIRIN; CIRRHOSIS; FIBROSIS;
D O I
10.1016/j.jhep.2016.02.022
中图分类号
R57 [消化系及腹部疾病];
学科分类号
摘要
Background & Aims: Recent clinical trials of direct-acting-antiviral agents (DAAs) against hepatitis C virus (HCV) achieved >90% sustained virological response (SVR) rates, suggesting that cure often took place before the end of treatment (EOT). We sought to evaluate retrospectively whether early response kinetics can provide the basis to individualize therapy to achieve optimal results while reducing duration and cost. Methods: 58 chronic HCV patients were treated with 12-week sofosbuvir + simeprevir (n = 19), sofosbuvir + daclatasvir (n = 19), or sofosbuvir + ledipasvir in three French referral centers. HCV was measured at baseline, day 2, every other week, EOT and 12 weeks post EOT. Mathematical modeling was used to predict the time to cure, i.e., <1 virus copy in the entire extracellular body fluid. Results: All but one patient who relapsed achieved SVR. Mean age was 60 +/- 11 years, 53% were male, 86% HCV genotype-1, 9% HIV coinfected, 43% advanced fibrosis (F3), and 57% had cirrhosis. At weeks 2, 4 and 6, 48%, 88% and 100% of patients had HCV <15 IU/ml, with 27%, 74% and 91% of observations having target not detected, respectively. Modeling results predicted that 23 (43%), 16 (30%), 7 (13%), 5 (9%) and 3 (5%) subjects were predicted to reach cure within 6, 8, 10, 12 and 13 weeks of therapy, respectively. The modeling suggested that the patient who relapsed would have benefitted from an additional week of sofosbuvir + ledipasvir. Adjusting duration of treatment according to the modeling predicts reduced medication costs of 43-45% and 17-30% in subjects who had HCV <15 IU/ml at weeks 2 and 4, respectively. Conclusions: The use of early viral kinetic analysis has the potential to individualize duration of DAA therapy with a projected average cost saving of 16-20% per 100-treated persons. (C) 2016 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.
引用
收藏
页码:1232 / 1239
页数:8
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