MODELING HIV AND T LYMPHOCYTE DYNAMICS

描述：(改编自摘要)组合数学建模 通过实验增加了人们对 人类感染HIV-1的基础过程。通过分析 使用有效的抗逆转录病毒药物扰乱 病毒载量处于准稳定状态的患者，主要 调查员和他的同伙能够确定艾滋病毒 在受感染的人中复制的几率很高。比较 通过数学模型的实验数据，研究人员得出结论 在平均每个HIV患者中，至少有100亿个病毒粒子 产生，释放到细胞外液中，每天清除。 此外，还估算了血浆中游离病毒粒子的半衰期(t1/2 6小时或更短的时间，这些细胞，大概是CD4+T细胞， 负责93-99%的稳态病毒产生有T1/2 1.6天或更少。剩下的病毒粒子似乎是由一种 T1/2介于1和4之间而腐烂的寿命更长的隔室 几周。在此应用程序中，调查员提出了各种 旨在扩大我们对病毒和淋巴细胞的了解的研究 动力学，以及抗药性的演变。 具体地说，调查员建议：(1)放宽假设 在此基础上，我们目前对病毒粒子清除率和 T1/2的高效感染细胞基于--抗病毒治疗 是100%有效的，目标细胞数量的增加可以 忽略--并研究后果；(2)扩展我们的建模和 血液和淋巴组织中的病毒粒子和淋巴细胞的分析， 并详细分析了病毒粒子对毛囊树突状细胞的捕获 单元格；(3)开发明确考虑这种可能性的模型 已有治疗和/或由以下原因引起的耐药病毒粒子 在抗病毒治疗期间的突变，并检查在 以下哪种病毒可以被根除或维持在低水平 治疗；以及(4)检查T细胞在体内的种群动态 患者在抗病毒治疗前和治疗期间都有助于阐明 幼稚细胞增殖、凋亡、新生生成的作用 细胞，以及细胞转运中观察到的T淋巴细胞的恢复。在……里面 除了获得基本了解外，调查员还建议 将这些信息应用到实际环境中，并与之互动 临床小组参与设计和评估新的治疗方案。

DESCRIPTION: (adapted from the Abstract) Mathematical modeling combined with experimentation has led to the increased understanding of the processes that underlie HIV-1 infection in humans. By analyzing experiments in which potent antiretroviral agents were used to perturb patients whose viral loads were in quasi-steady state, the Principal Investigator and his associates, were able to determine that HIV replication occurs at high rates in infected people. Comparing experimental data with mathematical models these researchers concluded that in the average HIV patient at least 10 billion virions are produced, released into the extracellular fluid, and cleared per day. Further, the half-live (t1/2) of free virions in plasma was estimated to be 6 hours or less, and that the cells, presumably CD4+ T Cells, responsible for 93-99% of the steady state viral production have a t1/2 of 1.6 days or less. The remaining virions appear to be produced by a longer-lived compartment that decays with a t1/2 of between 1 and 4 weeks. In this application, the Investigator proposes a variety of studies aimed at extending our understanding of viral and lymphocyte dynamics, and the evolution of drug resistance. Specifically, the Investigator proposes: (1) to relax the assumptions upon which our current estimates of the rate of virion clearance and the t1/2 of productively infected cells were based--that antiviral therapy is 100% effective and that the increase in target cell numbers can be ignored--and study the consequences; (2) to extend our modeling and analysis to virions and lymphocytes in both blood and lymphoid tissue, and analyze explicitly the trapping of virions on follicular dendritic cells; (3) to develop models that consider explicitly the possibility of drug resistant virions pre-existing treatment and/or arising by mutation during antiviral therapy and to examine the conditions under which virus might be eradicated or maintained at low levels by continued therapy; and (4) to examine the population dynamics of T cells within patients both before and during antiviral therapy to help elucidate the roles of cell proliferation, apoptosis, de novo generation of naive cells, and cell trafficking in observed recovery of T lymphocytes. In addition to gaining basic understanding the Investigator proposes putting this information into a practical setting, and to interact with clinical groups in the design and evaluation of new treatment protocols.