HCV kinetic and modeling analyses indicate similar time to cure among sofosbuvir combination regimens with daclatasvir, simeprevir or ledipasvir.
HCV kinetic and modeling analyses indicate similar time to cure among sofosbuvir combination regimens with daclatasvir, simeprevir or ledipasvir.
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HCV动力学和建模分析表明，与Daclatasvir，Simeprevir或Ledipasvir之间的Sofosbuvir组合方案之间的治疗时间相似。
DOI：
10.1016/j.jhep.2016.02.022
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发表时间：
2016-06
影响因子：
25.7
通讯作者：
Halfon P
中科院分区：
文献类型：
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作者：
Dahari H;Canini L;Graw F;Uprichard SL;Araújo ES;Penaranda G;Coquet E;Chiche L;Riso A;Renou C;Bourliere M;Cotler SJ;Halfon P
最近针对丙型肝炎病毒（HCV）的直接作用抗病毒药物（DAA）的临床试验达到了>90%的持续病毒学应答（SVR）率，表明治愈通常发生在治疗结束（EOT）之前。我们试图回顾性评估早期反应动力学是否可以提供个体化治疗的基础，以达到最佳效果，同时减少持续时间和成本。在三个法国转诊中心，58名慢性HCV患者接受了12周的索非布韦+西米普韦（n= 19），索非布韦+达卡他韦（n=19）或索非布韦+雷迪帕韦治疗。在基线、第2天、每隔一周、EOT和EOT后12周测量HCV。使用数学建模来预测治愈时间，即在整个细胞外体液中<1个病毒拷贝。除1例复发患者外，所有患者均实现了SVR。平均年龄为60±11岁，53%为男性，86%为HCV基因型-1，9%为HIV合并感染，43%为晚期纤维化（F3），57%为肝硬化。在第2、4和6周，48%、88%和100%的患者的HCV<15 IU/ml，分别有27%、74%和91%的观察结果未检测到目标。建模结果预测，分别有32例（43%）、16例（23%）、7例（13%）、5例（9%）和3例（5%）受试者在治疗6、8、10、12和13周内达到治愈。模型表明，复发的患者将受益于额外一周的sofosbuvir+ledipasvir。根据模型调整治疗持续时间预测，在第2周和第4周HCV<15 IU/ml的受试者中，药物费用分别减少43%-45%和17%-30%。早期病毒动力学分析的使用有可能使DAA治疗的持续时间个性化，预计每100名治疗人员的平均成本节省16%-20%。
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. 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. 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 32(43%), 16(23%), 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. 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.