Department of Physics, Ryerson University, Toronto, ON, Canada.
Department of Physics &Astronomy, Texas Christian University, Fort Worth, TX, USA.
Sci Rep. 2017 Jan 9;7:40210. doi: 10.1038/srep40210.
Antiviral therapy is a first line of defence against new influenza strains. Current pandemic preparations involve stock- piling oseltamivir, an oral neuraminidase inhibitor (NAI), so rapidly determining the effectiveness of NAIs against new viral strains is vital for deciding how to use the stockpile. Previous studies have shown that it is possible to extract the drug efficacy of antivirals from the viral decay rate of chronic infections. In the present work, we use a nonlinear mathematical model representing the course of an influenza infection to explore the possibility of extracting NAI drug efficacy using only the observed viral titer decay rates seen in patients. We first show that the effect of a time-varying antiviral concentration can be accurately approximated by a constant efficacy. We derive a relationship relating the true treatment dose and time elapsed between doses to the constant drug dose required to approximate the time- varying dose. Unfortunately, even with the simplification of a constant drug efficacy, we show that the viral decay rate depends not just on drug efficacy, but also on several viral infection parameters, such as infection and production rate, so that it is not possible to extract drug efficacy from viral decay rate alone.
抗病毒疗法是抵御新流感株的第一道防线。当前的大流行准备工作包括储备奥司他韦，一种口服神经氨酸酶抑制剂（NAI），因此，快速确定 NAI 对新病毒株的有效性对于决定如何使用储备至关重要。先前的研究表明，从慢性感染的病毒衰减率中可以提取抗病毒药物的疗效。在本工作中，我们使用代表流感感染过程的非线性数学模型来探索仅使用在患者中观察到的病毒滴度衰减率来提取 NAI 药物疗效的可能性。我们首先表明，随时间变化的抗病毒浓度的作用可以通过恒定的疗效来准确逼近。我们得出了一个关系，将真实的治疗剂量和剂量之间的时间间隔与近似时变剂量所需的恒定药物剂量联系起来。不幸的是，即使简化为恒定的药物疗效，我们也表明病毒衰减率不仅取决于药物疗效，还取决于几个病毒感染参数，例如感染和产生率，因此，仅从病毒衰减率中不可能提取药物疗效。
