Immune impairment thresholds in HIV infection
Immune impairment thresholds in HIV infection
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DOI：
10.1016/j.imlet.2009.03.007
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发表时间：
2009-04-27
影响因子：
4.4
通讯作者：
Miura, Tomoyuki
中科院分区：
文献类型：
--
作者：
Iwami, Shingo;Nakaoka, Shinji;Miura, Tomoyuki
对HIV-1感染者的纵向研究表明，从感染到发展为艾滋病，无症状期的时间很长，长短不一。一些艾滋病毒感染者在感染15年或更长时间后仍然没有症状，但一些患者在2年内发展为艾滋病。艾滋病的发病机制至今仍不清楚，但许多研究者一直在试图解释这一机制，如病毒多样性在艾滋病发病过程中的重要作用，尤其是Martin A.诺瓦克这些研究可以为无症状阶段的变异性提供一个优雅的解释。在这里，一个简单的数学模型被用来提出一个新的解释的可变长度的无症状阶段。其主要思想是，免疫损伤率增加超过艾滋病毒感染。我们的模型表明，存在所谓的“风险阈值”和“免疫缺陷阈值”的损害率。前者意味着当HIV的损伤率超过阈值时，免疫系统可能崩溃。后者意味着当损伤率超过该值时，免疫系统总是崩溃。我们发现，无症状期的长度取决于病毒学和免疫学状态，在这些阈值之间随机确定。此外，我们调查了一个HIV患者的无症状期的长度和免疫应答的存活率的分布。(C)2009爱思唯尔有限公司版权所有。
Longitudinal studies of patients infected with HIV-1 reveal a long and variable length of asymptomatic phase between infection and development of AIDS. Some HIV infected patients are still asymptomatic after 15 or more years of infection but some patients develop AIDS within 2 years. The mechanistic basis of the disease progression has remained obscure but many researchers have been trying to explain it. For example, the possible importance of viral diversity for the disease progression and the development of AIDS has been very well worked out in the early-1990s, especially by some important works of Martin A. Nowak. These studies can give an elegant explanation for a variability of asymptomatic phase. Here, a simple mathematical model was used to propose a new explanation for a variable length of asymptomatic phase. The main idea is that the immune impairment rate increases over the HIV infection. Our model suggested the existence of so-called "Risky threshold" and "Immunodeficiency threshold" on the impairment rate. The former implies that immune system may collapse when the impairment rate of HIV exceeds the threshold value. The latter implies that immune system always collapses when the impairment rate exceeds the value. We found that the length of asymptomatic phase is determined stochastically between these threshold values depending on the virological and immunological states. Furthermore, we investigated a distribution of the length of asymptomatic phase and a survival rate of the immune responses in one HIV patient. (C) 2009 Elsevier B.V. All rights reserved.