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基于模型的反应指导治疗在近期丙型肝炎感染患者中的应用。

Modeling based response guided therapy in subjects with recent hepatitis C infection.

机构信息

The Program for Experimental and Theoretical Modeling, Division of Hepatology, Department of Medicine, Stritch School of Medicine, Loyola University Medical Center, Maywood, IL, 60053, USA.

Kirby Institute, University of New South Wales, Sydney, NSW, Australia.

出版信息

Antiviral Res. 2020 Aug;180:104862. doi: 10.1016/j.antiviral.2020.104862. Epub 2020 Jun 25.

Abstract

BACKGROUND & AIMS: Mathematical modeling of viral kinetics has been shown to identify patients with chronic hepatitis C virus (HCV) infection who could be cured with a shorter duration of direct-acting antiviral (DAA) treatment. However, modeling therapy duration has yet to be evaluated in recently infected individuals. The aim of this study was to retrospectively examine whether modeling can predict outcomes of six-week sofosbuvir (SOF) and weight-based ribavirin (R) therapy in individuals with recent HCV infection.

METHODS

Modeling was used to estimate viral host parameters and to predict time to cure for 12 adults with recent HCV infection (<12 months of infection) who received six weeks of treatment with SOF + R.

RESULTS

Modeling results yielded a 100% negative predictive value for SOF + R treatment response in nine participants and suggested that a median of 13 [interquartile range: 8-16] weeks of therapy would be required for these patients to achieve cure. Modeling predicted cure after 5 weeks of therapy in the only modeled participant who achieved a sustained virological response. However, cure was also predicted for two participants who relapsed following treatment.

CONCLUSIONS

The modeling results confirm that longer than 6 weeks of SOF + R is needed to reach cure in individuals with recent HCV infection. Prospective real-time modeling under current potent DAA regimens is needed to validate the potential of response-guided therapy in the management of recent HCV infection.

摘要

背景与目的

病毒动力学的数学模型已被证明可以识别出慢性丙型肝炎病毒(HCV)感染患者,这些患者可以通过更短时间的直接作用抗病毒(DAA)治疗治愈。然而,模型治疗时间尚未在最近感染的个体中进行评估。本研究的目的是回顾性检查模型是否可以预测最近感染 HCV 的个体接受六周索非布韦(SOF)和基于体重的利巴韦林(R)治疗的结果。

方法

使用模型来估计病毒宿主参数,并预测 12 名最近 HCV 感染(<12 个月感染)接受 SOF+R 六周治疗的成年人的治愈时间。

结果

模型结果在 9 名参与者中对 SOF+R 治疗反应的阴性预测值为 100%,并表明这些患者需要中位数 13 周(四分位距:8-16)的治疗才能治愈。在唯一接受 5 周治疗后达到持续病毒学应答的模型参与者中,模型预测治疗 5 周后即可治愈。然而,在两名治疗后复发的参与者中也预测到了治愈。

结论

模型结果证实,最近感染 HCV 的个体需要超过 6 周的 SOF+R 治疗才能达到治愈。需要在当前有效的 DAA 方案下进行前瞻性实时建模,以验证基于反应的治疗在管理最近 HCV 感染中的潜力。

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