标题： 参数共振可能解释了HIV治疗中断后的病毒学失败 显示英文标题

标题： Parametric Resonance May Explain Virologic Failure to HIV Treatment Interruptions

摘要： 结构化治疗中断（STI）在HIV治疗中的试点研究显示，患者可以在减少治疗毒性的同时保持低病毒载量。 然而，最近的一项STI临床试验报告称出现了高度的病毒学失败。 在这里，我们提出一个新假设，可以解释STI的病毒学失败，并提供具有重要临床意义的新见解。 我们分析了一个经典的HIV体内病毒动力学数学模型，发现当将STI加入模型时会发生非线性参数共振；共振表现为病毒学失败。 我们使用该模型来模拟临床试验数据并计算个体患者的共振谱。 我们获得了两个重要的见解。 首先，在STI试验中，我们确定那些初始病毒载量相似的患者可能会由于共振而表现出极不同的病毒学反应。 因此，在STI临床试验中，患者反应的高度异质性是可以预期的。 其次，更为重要的是，我们确定病毒学失败不仅仅是由于STI或患者特征引起的；而是STI与患者病毒动力学之间复杂动态相互作用的结果。 因此，我们的分析表明，没有一种具有周期性中断的通用方案会对所有患者都有效。 基于我们的结果，我们建议应使用免疫学和病毒学参数来设计个体化的STI方案。 显示英文摘要

摘要： Pilot studies of structured treatment interruptions (STI) in HIV therapy have shown that patients can maintain low viral loads whilst benefiting from reduced treatment toxicity. However, a recent STI clinical trial reported a high degree of virologic failure. Here we present a novel hypothesis that could explain virologic failure to STI and provides new insights of great clinical relevance. We analyze a classic mathematical model of HIV within-host viral dynamics and find that nonlinear parametric resonance occurs when STI are added to the model; resonance is observed as virologic failure. We use the model to simulate clinical trial data and to calculate patient-specific resonant spectra. We gain two important insights. Firstly, within an STI trial, we determine that patients who begin with similar viral loads can be expected to show extremely different virologic responses as a result of resonance. Thus, high heterogeneity of patient response within a STI clinical trial is to be expected. Secondly and more importantly, we determine that virologic failure is not simply due to STI or patient characteristics; rather it is the result of a complex dynamic interaction between STI and patient viral dynamics. Hence, our analyses demonstrate that no universal regimen with periodic interruptions will be effective for all patients. On the basis of our results, we suggest that immunologic and virologic parameters should be used to design patient-specific STI regimens.