A numerical approach to solve the model for HIV infection of CD4+T cells

In this study, we will obtain the approximate solutions of the HIV infection model of CD4⁺T by developing the Bessel collocation method. This model corresponds to a class of nonlinear ordinary differential equation systems. Proposed scheme consists of reducing the problem to a nonlinear algebraic equation system by expanding the approximate solutions by means of the Bessel polynomials with unknown coefficients. The unknown coefficients of the Bessel polynomials are computed using the matrix operations of derivatives together with the collocation method. The reliability and efficiency of the proposed approach are demonstrated in the different time intervals by a numerical example. All computations have been made with the aid of a computer code written in Maple 9.     

Global dynamics of a mathematical model for HTLV-I infection of CD4 T cells with delayed CTL response

Human T-cell leukaemia virus type I (HTLV-I) preferentially infects the CD4⁺ T cells. The HTLV-I infection causes a strong HTLV-I specific immune response from CD8⁺ cytotoxic T cells (CTLs). The persistent cytotoxicity of the CTL is believed to contribute to the development of a progressive neurologic disease, HTLV-I associated myelopathy/tropical spastic paraparesis (HAM/TSP). We investigate the global dynamics of a mathematical model for the CTL response to HTLV-I infection in vivo. To account for a series of immunological events leading to the CTL response, we incorporate a time delay in the response term. Our mathematical analysis establishes that the global dynamics are determined by two threshold parameters R₀ and R₁, basic reproduction numbers for viral infection and for CTL response, respectively. If R₀≤1, the infection-free equilibrium P₀ is globally asymptotically stable, and the HTLV-I viruses are cleared. If R₁≤1<R₀, the asymptomatic-carrier equilibrium P₁ is globally asymptotically stable, and the HTLV-I infection becomes chronic but with no persistent CTL response. If R₁>1, a unique HAM/TSP equilibrium P₂ exists, at which the HTLV-I infection is chronic with a persistent CTL response. We show that the time delay can destabilize the HAM/TSP equilibrium, leading to Hopf bifurcations and stable periodic oscillations. Implications of our results to the pathogenesis of HTLV-I infection and HAM/TSP development are discussed.     

A Delayed HIV Infection Model with the Homeostatic Proliferation of CD4+ T Cells

In this paper, we investigate a delayed HIV infection model that considers the homeostatic proliferation of CD4⁺ T cells. The existence and stability of uninfected equilibrium and infected equilibria(smaller and larger ones) are studied by analyzing the characteristic equation of the system. The intracellular delay does not affect the stability of uninfected equilibrium, but it can change the stability of larger positive equilibrium and Hopf bifurcation appears inducing stable limit c...     

The role of CD4 T cells in immune system activation and viral reproduction in a simple model for HIV infection

CD4 T cells play a fundamental role in the adaptive immune response including the stimulation of cytotoxic lymphocytes (CTLs). Human immunodeficiency virus (HIV) which infects and kills CD4 T cells causes progressive failure of the immune system. However, HIV particles are also reproduced by the infected CD4 T cells. Therefore, during HIV infection, infected and healthy CD4 T cells act in opposition to each other, reproducing virus particles and activating and stimulating cellular immune responses, respectively. In this investigation, we develop and analyze a simple system of four ordinary differential equations that accounts for these two opposing roles of CD4 T cells. The model illustrates the importance of the CTL immune response during the asymptomatic stage of HIV infection. In addition, the solution behavior exhibits the two stages of infection, asymptomatic and final AIDS stages. In the model, a weak immune response results in a short asymptomatic stage and faster development of AIDS, whereas a strong immune response illustrates the long asymptomatic stage. A model with a latent stage for infected CD4 T cells is also investigated and compared numerically with the original model. The model shows that strong stimulation of CTLs by CD4 T cells is necessary to prevent progression to the AIDS stage.     

一类带有治愈率的HIV感染的CD4＋T细胞模型的动力学性质

本文主要介绍一类带有治愈率的HIV感染的CD4 T细胞模型的动力学性质,同时证明了如果基本再生数R0＜1,HIV感染消失;如果R0＞1,HIV感染持续.然后进行数值模拟,给出了地方性平衡点E·全局稳定的参数域,得到了地方性平衡点E·不稳定时周期解存在.     

Dynamics of reaction–diffusion equations for modeling CD4+ T cells decline with general infection mechanism and distinct dispersal rates

In this paper, we are concerned with a diffusive viral infection dynamical model with general infection mechanism and distinct dispersal rates. In a general setting in which the model parameters are spatially heterogeneous, it is shown that if ${ℛ}_0\le 1$, the infection-free steady state is globally asymptotically stable; while if ${ℛ}_0>1$, the model is uniformly persistent. The asymptotic profiles of the infection steady state are discussed as the dispersal rate of uninfected CD4${}^{+}$ T cells approaches zero by means of the persistence theory of semidynamical systems and the eigenvalue theory of elliptic equations.     

具有感染年龄结构的CD4+ T-细胞感染HIV病毒模型分析

本文建立和研究一类具有感染年龄结构的CD4+ T-细胞感染HIV病毒的动力学模型.得到决定该模型的未感染平衡点和感染平衡点的存在性和局部渐近稳定性条件,即当一个感染细胞在其整个感染期间产生病毒的总数不超过某-个阈值时,系统总存在局部渐近稳定的未感染平衡点;当-个感染细胞在其整个感染期间产生病毒的总数超过这一阈值时,未感染平衡点不稳定,此时存在局部渐近稳定的感染平衡点.     

Global dynamics of a mathematical model for HTLV-I infection of CD4 T-cells

In this paper, a mathematical model for HILV-I infection of CD4⁺ T-cells is investigated. The force of infection is assumed be of a function in general form, and the resulting incidence term contains, as special cases, the bilinear and the saturation incidences. The model can be seen as an extension of the model [Wang et al. Mathematical analysis of the global dynamics of a model for HTLV-I infection and ATL progression, Math. Biosci. 179 (2002) 207-217; Song, Li, Global stability and periodic solution of a model for HTLV-I infection and ATL progression, Appl. Math. Comput. 180(1) (2006) 401-410]. Mathematical analysis establishes that the global dynamics of T-cells infection is completely determined by a basic reproduction number _R0${\mathfrak{R}}_0$. If _R0?1${\mathfrak{R}}_0?1$, the infection-free equilibrium is globally stable; if _R0>1${\mathfrak{R}}_0>1$, the unique infected equilibrium is globally stable in the interior of the feasible region.     

Small world network models of the dynamics of HIV infection

It has long been recognised that the structure of social networks plays an important role in the dynamics of disease propagation. The spread of HIV results from a complex network of social interactions and other factors related to culture, sexual behaviour, demography, geography and disease characteristics, as well as the availability, accessibility and delivery of healthcare. The small world phenomenon has recently been used for representing social network interactions. It states that, given some random connections, the degrees of separation between any two individuals within a population can be very small. In this paper we present a discrete event simulation model which uses a variant of the small world network model to represent social interactions and the sexual transmission of HIV within a population. We use the model to demonstrate the importance of the choice of topology and initial distribution of infection, and capture the direct and non-linear relationship between the probability of a casual partnership (small world randomness parameter) and the spread of HIV. Finally, we illustrate the use of our model for the evaluation of interventions such as the promotion of safer sex and introduction of a vaccine.     

A differential equation model of HIV infection of CD4T-cells with cure rate

A differential equation model of HIV infection of CD4⁺T-cells with cure rate is studied. We prove that if the basic reproduction number R₀<1, the HIV infection is cleared from the T-cell population and the disease dies out; if R₀>1, the HIV infection persists in the host. We find that the chronic disease steady state is globally asymptotically stable if R₀>1. Furthermore, we also obtain the conditions for which the system exists an orbitally asymptotically stable periodic solution. Numerical simulations are presented to illustrate the results.     

HIV dynamics: Modeling,data analysis,and optimal treatment protocols

We present an overview of some concepts and methodologies we believe useful in modeling HIV pathogenesis. After a brief discussion of motivation for and previous efforts in the development of mathematical models for progression of HIV infection and treatment, we discuss mathematical and statistical ideas relevant to Structured Treatment Interruptions (STI). Among these are model development and validation procedures including parameter estimation, data reduction and representation, and optimal control relative to STI. Results from initial attempts in each of these areas by an interdisciplinary team of applied mathematicians, statisticians and clinicians are presented.     

The Modeling Dynamics of HIV and CD4$$^{}$$ T-cells During Primary Infection in Fractional Order: Numerical Simulation

This article is devoted to introduce a numerical treatment using Adams–Bashforth–Moulton method of the fractional model of HIV-1 infection of CD4\(^{+}\) T-cells. We study the effect of the changing the average number of viral particles N with different sets of initial conditions on the dynamics of the presented model. The fractional derivative is described in Caputo sense. Special attention is given to present the local stability of the proposed model using fractional Routh–Hurwitz stability criterion. Qualitative results show that the model has two equilibria: the disease-free equilibrium and the endemic equilibrium points. We compare our numerical solutions with those numerical solutions using fourth-order Runge–Kutta method (RK4). The obtained numerical results of the proposed model show the simplicity and the efficiency of the proposed method.     

Global dynamics of delay‐distributed HIV infection models with differential drug efficacy in cocirculating target cells

In this paper, we investigate the dynamical behaviors of three human immunodeficiency virus infection models with two types of cocirculating target cells and distributed intracellular delay. The models take into account both short‐lived infected cells and long‐lived chronically infected cells. In the two types of target cells, the drug efficacy is assumed to be different. The incidence rate of infection is given by bilinear and saturation functional responses in the first and second models, respectively, while it is given by a general function in the third model. Lyapunov functionals are constructed and LaSalle invariance principle is applied to prove the global asymptotic stability of all equilibria of the models. We have derived the basic reproduction number R₀ for the three models. For the first two models, we have proven that the disease‐free equilibrium is globally asymptotically stable (GAS) when R₀≤1, and the endemic equilibrium is GAS when R₀>1. For the third model, we have established a set of sufficient conditions for global stability of both equilibria of the model. We have checked our theoretical results with numerical simulations. Copyright © 2015 John Wiley & Sons, Ltd.     

Modeling and dynamics of HIV transmission among high-risk groups in Guangzhou city, China

In this paper, a multicompartmental model is formulated to study how HIV is transmitted among different HIV high-risk groups, including MSM (men who have sex with men), FRs (foreigner residents), FSWs (female sex workers), and IDUs (injection drug users). The explicit expression for the basic reproduction number is obtained via the next generation matrix approach. We show that the disease free equilibrium is locally as well as globally asymptotically stable (the disease goes to extinction) when the basic reproduction number is less than unity, and the disease is always present when the basic reproduction number is larger than unity. As an illustration of our theoretical results, we conduct numerical simulations. We also conduct a case study where model parameters are estimated from the demographic and epidemiological data from Guangzhou. Using the parameter estimates, we predict the HIV/AIDS trend for each high-risk group. Furthermore, our study suggests that reducing the transmission routes of the disease and increasing condom use will be useful for control of HIV transmission.     

基于CD4细胞计数的HIV仓室模型与数据分析

迄今我国每年统计艾滋病的新增人数与死亡人数仍呈上升趋势,由于潜伏期长和初期无明显症状等原因,还存在大量未发现的HIV携带者,这给HIV的防控带来巨大挑战.旨在利用中国疾控中心网报数据和深圳市患者随访数据,结合传染病动力学和统计分析方法与临床知识,建立依微观CD4细胞计数划分的宏观HIV仓室数学模型,通过数值计算方法与MCMC参数估计方法实现稳健的参数拟合,进而利用不确定性和敏感性以及随机森林方法进行灵敏度分析.研究结果表明:2013年广东省未确诊HIV携带者约为13.1061万人,且该地区HIV疫情传播的基本再生数为2.8133.敏感性分析揭示艾滋病疫情防控最优方法是控制患者有效接触人数与沉默系数,由此建议制定针对控制艾滋病传播中一些现象的法律法规,在艾滋病高发地区实施清洁针具交换工作等,对疫情防控提出指导性建议.     

Modeling the dynamical impact of HIV on the immune system: Viral clearance,infection, and AIDS

A phenomenological model simulating the time-dependent consequences of the HIV challenge on the immune system is presented. One of the important features of the model is its ability to handle T helper cell production and apoptosis (genetically determined suicide). The values of the independent, generally time-dependent, model parameters were chosen to be compatible with known experimental data. A new approach to the numerical solution of the resulting coupled, nonlinear model equations is presented, and simulations of a typical viral challenge that is cleared and one that leads to infection and AIDS are exhibited.It is shown that a change in the saturated value of a single model parameter is sufficient to change a simulated challenge on its way to being cleared into one that leads to infection instead (and vice versa). If the saturated values of all of the independent model parameters are known at the beginning of a challenge, the outcome of the challenge can be predicted in advance. If the virulence of the HIV strain (defined in this paper) is above a critical threshold at inoculation, infection will result regardless of the initial viral load. This latter result could explain why accidental HIV contaminated needle sticks sometime result in infection regardless of the counter-measures undertaken.A model simulating the time evolution of the collapse of the T helper cell density leading to AIDS is introduced. This model consists of immunological and mathematical parts and is compatible with experimental data. The immediate cause of the beginning of this collapse is postulated to be a spontaneous mutation of the virus into a more virulent form that not only leads to an explosion in the viral load but also to a dramatic increase in the level of induced apoptosis of T helper cells. The results of this model are consistent with the known experimental behavior of the viral load and T helper cell densities in the final stage of HIV infection.     

Modeling the dynamics of block-and-fault systems and seismicity

A model of block-and-fault system dynamics (a block model) has been developed to analyze how the basic features of seismicity depend on the lithosphere structure in a region under consideration and on the peculiarities of the lithosphere dynamics. The lithosphere in the region is modeled by a system of perfectly rigid blocks divided by infinitely thin fault planes. The viscoelastic interaction between the blocks and with the underlying medium is specified. Displacements and rotations of the blocks at each time are determined so that the whole block system is in a quasi-static equilibrium state. When the ratio of the stress to the pressure exceeds the critical level in some part of a fault zone, a stress drop occurs that is considered in the model as an earthquake. The paper contains a review of results obtained by numerical simulation of the dynamics of different block structures including the structures approximating the lithosphere structure in specific seismic regions. These results suggest that the block model is a useful tool for studying the influence of geometry of faults and motions of blocks on seismicity features.