週一 3/5 晚上七點 生科館四樓 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 病毒感染是現今公共衛生上極為重要的一個問題，尤其像人體免疫缺陷病毒(HIV)、B型 肝炎病毒、C型肝炎病毒在感染過程中，會抑制人體本身的免疫反應，使得痊癒更為困難 。是以，近來許多人開始採用一種新的治療策略：增強人體本身的免疫反應，以對抗造 成感染的病毒。這種療程常包含「中斷給藥」的過程。在這一篇文章中，作者以簡單的 數學模型來模擬病毒感染，描述免疫反應與病毒數量的變化、關係；並用數學模型說明 增強免疫的可能，發展出一套利用人體本身免疫力來控制病毒感染的治療策略。在這一 套治療策略中，給藥的時間、藥物效力的強弱必須被完善瞭解、控制，選在免疫反應增 強、且未再度削弱之時停止給藥，以達到預期的效果。並且，作者把模擬的結果與實際 觀察的案例比對，認為這套模型有不錯的實用價值，可以用於治療病毒感染。 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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