周一 3/5 晚上七点 生科馆四楼 Natalia L. Komarova, Eleanor Barne, Paul Klenerman, and Dominik Wodarz Boosting immunity by antiviral drug therapy: A simple relationship among timing, efficacy, and success. PNAS February 18, 2003 vol. 100 no. 4 1855–1860 病毒感染是现今公共卫生上极为重要的一个问题，尤其像人体免疫缺陷病毒(HIV)、B型 肝炎病毒、C型肝炎病毒在感染过程中，会抑制人体本身的免疫反应，使得痊癒更为困难 。是以，近来许多人开始采用一种新的治疗策略：增强人体本身的免疫反应，以对抗造 成感染的病毒。这种疗程常包含「中断给药」的过程。在这一篇文章中，作者以简单的 数学模型来模拟病毒感染，描述免疫反应与病毒数量的变化、关系；并用数学模型说明 增强免疫的可能，发展出一套利用人体本身免疫力来控制病毒感染的治疗策略。在这一 套治疗策略中，给药的时间、药物效力的强弱必须被完善了解、控制，选在免疫反应增 强、且未再度削弱之时停止给药，以达到预期的效果。并且，作者把模拟的结果与实际 观察的案例比对，认为这套模型有不错的实用价值，可以用於治疗病毒感染。 Drug therapies against persistent human infections such as hepatitis C virus, hepatitis B virus, and HIV fail to consistently eradicate the infection from the host. Hence, recent emphasis has shifted to the study of antiviral therapy aimed at boosting specific immune responses. It was argued that structured therapy interruptions were required to achieve this, because such regimes have shown promising results in early HIV infection. Using mathematical models, we show that, contrary to this notion, a single phase of drug therapy can result in the establishment of sustained immunity. We present a simple relationship between timing of therapy and efficacy of the drugs required for success. In the presence of strong viral suppression, we show that therapy should be stopped relatively early, and that a longer duration of treatment leads to failure. On the other hand, in the presence of weaker viral suppression, stopping treatment too early is detrimental, and therapy has to be continued beyond a time threshold. We discuss our modeling results primarily in the context of HCV therapy during chronic infection. Although the therapy regimes explored here also have implications for HIV, virus-mediated destruction of specific immune cells renders success unlikely during the chronic phase of the infection. --

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