Müller V, Marée A F, De Boer R J
Department of Plant Taxonomy and Ecology, Eötvös Lorand University, Budapest, Hungary.
Proc Biol Sci. 2001 Feb 7;268(1464):235-42. doi: 10.1098/rspb.2000.1358.
Steady-state levels of HIV-1 viraemia in the plasma vary more than a 1,000-fold between HIV-positive patients and are thought to be influenced by several different host and viral factors such as host target cell availability, host anti-HIV immune response and the virulence of the virus. Previous mathematical models have taken the form of classical ecological food-chain models and are unable to account for this multifactorial nature of the disease. These models suggest that the steady-state viral load (i.e. the set-point) is determined by immune response parameters only. We have devised a generalized consensus model in which the conventional parameters are replaced by so-called 'process functions'. This very general approach yields results that are insensitive to the precise form of the mathematical model. Here we applied the approach to HIV-1 infections by estimating the steady-state values of several process functions from published patient data. Importantly, these estimates are generic because they are independent of the precise form of the underlying processes. We recorded the variation in the estimated steady-state values of the process functions in a group of HIV-1 patients. We developed a novel model by providing explicit expressions for the process functions having the highest patient-to-patient variation in their estimated values. Small variations from patient to patient for several parameters of the new model collectively accounted for the large variations observed in the steady-state viral burden. The novel model remains in full agreement with previous models and data.
血浆中HIV-1病毒血症的稳态水平在HIV阳性患者之间的差异超过1000倍，并且被认为受到多种不同的宿主和病毒因素影响，如宿主靶细胞的可获得性、宿主抗HIV免疫反应以及病毒的毒力。先前的数学模型采用经典生态食物链模型的形式，无法解释该疾病的这种多因素性质。这些模型表明稳态病毒载量（即设定点）仅由免疫反应参数决定。我们设计了一个广义共识模型，其中传统参数被所谓的“过程函数”所取代。这种非常通用的方法产生的结果对数学模型的精确形式不敏感。在这里，我们通过从已发表的患者数据中估计几个过程函数的稳态值，将该方法应用于HIV-1感染。重要的是，这些估计是通用的，因为它们独立于潜在过程的精确形式。我们记录了一组HIV-1患者中过程函数估计稳态值的变化。我们通过为估计值患者间差异最大的过程函数提供明确表达式，开发了一个新模型。新模型几个参数在患者间的小差异共同解释了稳态病毒载量中观察到的大差异。新模型与先前的模型和数据完全一致。
