Global properties of a class of HIV infection models with Beddington–DeAngelis functional response

In this paper, the global properties of a class of human immunodeficiency virus (HIV) models with Beddington–DeAngelis functional response are investigated. Lyapunov functions are constructed to establish the global asymptotic stability of the uninfected and infected steady states of three HIV infection models. The first model considers the interaction process of the HIV and the CD4 ⁺ T cells and takes into account the latently and actively infected cells. The second model describes two co‐circulation populations of target cells, representing CD4 ⁺ T cells and macrophages. The third model is a two‐target‐cell model taking into account the latently and actively infected cells. We have proven that if the basic reproduction number R₀ is less than unity, then the uninfected steady state is globally asymptotically stable, and if R₀ > 1, then the infected steady state is globally asymptotically stable. Copyright © 2012 John Wiley & Sons, Ltd.     

Dynamics of an age‐structured host‐vector model for malaria transmission

In this paper, we propose a host‐vector model for malaria transmission by incorporating infection age in the infected host population and nonlinear incidence for transmission from infectious vectors to susceptible hosts. One novelty of the model is that the recovered hosts only have temporary immunity and another is that successfully recovered infected hosts may become susceptible immediately. Firstly, the existence and local stability of equilibria is studied. Secondly, rigorous mathematical analyses on technical materials and necessary arguments, including asymptotic smoothness and uniform persistence of the system, are given. Thirdly, by applying the fluctuation lemma and the approach of Lyapunov functionals, the threshold dynamics of the model for a special case were established. Roughly speaking, the disease‐free equilibrium is globally asymptotically stable when the basic reproduction number is less than one and otherwise the endemic equilibrium is globally asymptotically stable when no reinfection occurs. It is shown that the infection age and nonlinear incidence not only impact on the basic reproduction number but also could affect the values of the endemic steady state. Numerical simulations were performed to support the theoretical results.     

Global dynamics of a viral infection model with a latent period and Beddington-DeAngelis response

In this paper, we study the global dynamics of a viral infection model with a latent period. The model has a nonlinear function which denotes the incidence rate of the virus infection in vivo. The basic reproduction number of the virus is identified and it is shown that the uninfected equilibrium is globally asymptotically stable if the basic reproduction number is equal to or less than unity. Moreover, the virus and infected cells eventually persist and there exists a unique infected equilibrium which is globally asymptotically stable if the basic reproduction number is greater than unity. The basic reproduction number determines the equilibrium that is globally asymptotically stable, even if there is a time delay in the infection.     

Global stability of an HIV-1 infection model with saturation infection and intracellular delay

In this paper, an HIV-1 infection model with a saturation infection rate and an intracellular delay accounting for the time between viral entry into a target cell and the production of new virus particles is investigated. By analyzing the characteristic equations, the local stability of an infection-free equilibrium and a chronic-infection equilibrium of the model is established. By using suitable Lyapunov functionals and the LaSalle invariant principle, it is proved that if the basic reproduction ratio is less than unity, the infection-free equilibrium is globally asymptotically stable; if the basic reproduction ratio is greater than unity, the chronic-infection equilibrium is globally asymptotically stable.     

Stability and Hopf Bifurcation of a Virus Infection Model with a Delayed CTL Immune Response

In this paper, a virus infection model with standard incidence rate and delayed CTL immune response is investigated. By analyzing corresponding characteristic equations, the local stability of each of feasible equilibria and the existence of Hopf bifurcations at the CTL-activated infection equilibrium are established, respectively. By means of comparison arguments, it is verified that the infection-free equilibrium is globally asymptotically stable if the basic reproduction ratio is less than unity. By using suitable Lyapunov functional and LaSalle＇s invariance principle, it is shown that the CTL-inactivated infection equilibrium of the system is globally asymptotically stable if tile immune response reproduction ratio is less than unity and the basic reproduction ratio is greater than unity. Numerical simulations are carried out to illustrate the theoretical result.     

A HIV Infection Model with Periodic Multidrug Therapy

This paper investigates the effects of periodic drug treatment on a HIV infection model with two co-circulation populations of target cells. We first introduce the basic reproduction ratio for the model, and then show that the infection free equilibrium is globally asymptotically stable if R0 < 1, while the infection persists and there exists at least one positive periodic state when R0 > 1. Therefore, R0 serves as a threshold parameter for the infection. We then consider an optimization problem by shifting the phase of drug efficacy functions, which corresponds to change the dosage time of drugs in each time interval. It turns out that shifting the phase affect critically on the stability of the infection free steady state. Finally, exhaustive numerical simulations are carried out to support our theoretical analysis and explore the optimal phase shift.     

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.     

Mathematical model for the dynamics of visceral leishmaniasis–malaria co‐infection

A mathematical model to understand the dynamics of malaria–visceral leishmaniasis co‐infection is proposed and analyzed. Results show that both diseases can be eliminated if R₀, the basic reproduction number of the co‐infection, is less than unity, and the system undergoes a backward bifurcation where an endemic equilibrium co‐exists with the disease‐free equilibrium when one of R_m or R_l, the basic reproduction numbers of malaria‐only and visceral leishmaniasis‐only, is precisely less than unity. Results also show that in the case of maximum protection against visceral leishmaniasis (VL), the disease‐free equilibrium is globally asymptotically stable if malaria patients are protected from VL infection; similarly, in the case of maximum protection against malaria, the disease‐free equilibrium is globally asymptotically stable if VL and post‐kala‐azar dermal leishmaniasis patients and the recovered humans after VL are protected from malaria infection. Numerical results show that if R_m and R_l are greater than unity, then we have co‐existence of both disease at an endemic equilibrium, and malaria incidence is higher than visceral leishmaniasis incidence at steady state. Copyright © 2016 John Wiley & Sons, Ltd.     

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.     

Global dynamics of an age‐structured virus model with saturation effects

An infection‐age virus dynamics model for human immunodeficiency virus (or hepatitis B virus) infections with saturation effects of infection rate and immune response is investigated in this paper. It is shown that the global dynamics of the model is completely determined by two critical values R ₀, the basic reproductive number for viral infection, and R ₁, the viral reproductive number at the immune‐free infection steady state (R ₁<R ₀). If R ₀<1, the uninfected steady state E ⁰ is globally asymptotically stable; if R ₀>1 > R ₁, the immune‐free infected steady state E ^? is globally asymptotically stable; while if R ₁>1, the antibody immune infected steady state is globally asymptotically stable. Moreover, our results show that ignoring the saturation effects of antibody immune response or infection rate will result in an overestimate of the antibody immune reproductive number. Copyright © 2016 John Wiley & Sons, Ltd.     

An age-structured within-host HIV model with T-cell competition

Recent studies demonstrate that resource competition is an essential component of T-cell proliferation in HIV progression, which can contribute instructively to the disease development. In this paper, we formulate an age-structured within-host HIV model, in the form of a hyperbolic partial differential equation (PDE) for infected target cells coupled with two ordinary differential equations for uninfected T-cells and the virions, to explore the effects of both the T-cell competition and viral shedding variations on the viral dynamics. The basic reproduction number is derived for a general viral production rate which determines the local stability of the infection-free equilibrium. Two special forms of viral production rates, which are extensively investigated in previous literature, the delayed exponential distribution and a step function rate, are further investigated, where the original system can be reduced into systems of delay differential equations. It is confirmed that there exists a unique positive equilibrium for two special viral production rates when the basic reproduction number is greater than one. However, the model exhibits the phenomenon of backward bifurcation, where two positive steady states coexist with the infection-free equilibrium when the basic reproduction number is less than one.     

Bifurcation analysis of HIV infection model with antibody and cytotoxic T‐lymphocyte immune responses and Beddington–DeAngelis functional response

In this paper, a mathematical model for HIV‐1 infection with antibody, cytotoxic T‐lymphocyte immune responses and Beddington–DeAngelis functional response is investigated. The stability of the infection‐free and infected steady states is investigated. The basic reproduction number R₀ is identified for the proposed system. If R₀ < 1, then there is an infection‐free steady state, which is locally asymptotically stable. Further, the infected steady state is locally asymptotically stable for R₀ > 1 in the absence of immune response delay. We use Nyquist criterion to estimate the length of the delay for which stability continues to hold. Also the existence of the Hopf bifurcation is investigated by using immune response delay as a bifurcation parameter. Numerical simulations are presented to justify the analytical results. Copyright © 2014 John Wiley & Sons, Ltd.     

Global stability analysis and permanence for an HIV-1 dynamics model with distributed delays

This paper mainly investigates the global asymptotic stabilities of two HIV dynamics models with two distributed intracellular delays incorporating Beddington-DeAngelis functional response infection rate. An eclipse stage of infected cells (i.e. latently infected cells), not yet producing virus, is included in our models. For the first model, it is proven that if the basic reproduction number $R_0$ is less than unity, then the infection-free equilibrium is globally asymptotically stable, and if $R_0 $ is greater than unity, then the infected equilibrium is globally asymptotically stable. We also obtain that the disease is always present when $R_0 $ is greater than unity by using a permanence theorem for infinite dimensional systems. What is more, a n-stage-structured HIV model with two distributed intracellular delays, which is the extensions to the first model, is developed and analyzed. We also prove the global asymptotical stabilities of two equilibria by constructing suitable Lyapunov functionals.     

一类具有饱和发生率及免疫的时滞SEIR传染病模型的全局渐近稳定性

研究了一类具有饱和发生率及免疫的SEIR,传染病模型、构造适当的Lyapunov泛函并运用时滞微分方程的LaSalle型定理,证明了当基本再生数小于1时,无病平衡点是全局渐进稳定的,当基本再生数大于1时,地方病平衡点存在并且是全局渐近稳定的.     

The global dynamics of a model about HIV-1 infection in vivo

A four dimension ODE model is built to study the infection of human immunodeficiency virus (HIV) in vivo. We include in this model four components: the healthy T cells, the latent-infected T cells, the active-infected T cells and the HIV virus. Two types of HIV transmissions in vivo are also included in the model: the virus-to-cell transmission, and the cell-to-cell HIV transmission. There are two possible equilibriums: the healthy equilibrium, and the infected steady state. The basic reproduction number R ₀ is introduced. When R ₀ < 1, the healthy equilibrium is globally stable and when R ₀ > 1, the infected equilibrium exists and is globally stable. Through simulations, we find that, the cell-to-cell HIV transmission is very important for the final outcome of the HIV attacking. Some important clinical observations about the HIV infection situation in lymph node are also verified.      

Global dynamics of a Vector‐Borne disease model with two delays and nonlinear transmission rate

In this paper, we investigate a Vector‐Borne disease model with nonlinear incidence rate and 2 delays: One is the incubation period in the vectors and the other is the incubation period in the host. Under the biologically motivated assumptions, we show that the global dynamics are completely determined by the basic reproduction number R₀. The disease‐free equilibrium is globally asymptotically stable if R₀≤1; when R₀>1, the system is uniformly persistent, and there exists a unique endemic equilibrium that is globally asymptotically. Numerical simulations are conducted to illustrate the theoretical results.     

Global dynamics of a intracellular infection model with delays and humoral immunity

A virus infection model with time delays and humoral immunity has been investigated. Mathematical analysis shows that the global dynamics of the model is fully determined by the basic reproduction numbers of the virus and the immune response, R₀ and R₁. The infection‐free equilibrium P₀ is globally asymptotically stable when R₀≤1. The infection equilibrium without immunity P₁ is globally asymptotically stable when R₁≤1 < R₀. The infection equilibrium with immunity P₂ is globally asymptotically stable when R₁>1. The expression of the basic reproduction number of the immune response R₁ implies that the immune response reduces the concentration of free virus as R₁>1. Copyright © 2016 John Wiley & Sons, Ltd.     

GLOBAL STABILITY IN A VIRAL INFECTION MODEL

This paper investigates the global stability of a viral infection model with lytic immune response. If the basic reproductive ratio of the virus is less than or equal to one, by the LaSalle's invariance principle, the disease-free steady state is globally asymptotically stable. If the basic reproductive ratio of the virus is greater than one but less than or equal to a constant, which is defined by the parameters of the model, then the immune-exhausted steady state is globally asymptotically stable. The endemic steady state is globally asymptotically stable if the inverse is valid.     

Global dynamics of a spatial heterogeneous viral infection model with intracellular delay and nonlocal diffusion

In this paper, we propose a spatial heterogeneous viral infection model, where heterogeneous parameters, the intracellular delay and nonlocal diffusion of free virions are considered. The global well-posedness, compactness and asymptotic smoothness of the semiflow generated by the system are established. It is shown that the principal eigenvalue problem of a perturbation of the nonlocal diffusion operator has a principal eigenvalue associated with a positive eigenfunction. The principal eigenvalue plays the same role as the basic reproduction number being defined as the spectral radius of the next generation operator. The existence of the unique chronic-infection steady state is established by the super-sub solution method. Furthermore, the uniform persistence of the model is investigated by using the persistence theory of infinite dimensional dynamical systems. By setting the eigenfunction as the integral kernel of Lyapunov functionals, the global threshold dynamics of the system is established. More precisely, the infection-free steady state is globally asymptotically stable if the basic reproduction number is less than one; while the chronic-infection steady state is globally asymptotically stable if the basic reproduction number is larger than one. Numerical simulations are carried out to illustrate the effects of intracellular delay and diffusion rate on the final concentrations of infected cells and free virions, respectively.     

Global properties for virus dynamics model with Beddington–DeAngelis functional response

This paper investigates the global stability of virus dynamics model with Beddington–DeAngelis infection rate. By constructing Lyapunov functions, the global properties have been analysed. If the basic reproductive ratio of the virus is less than or equal to one, the uninfected steady state is globally asymptotically stable. If the basic reproductive ratio of the virus is more than one, the infected steady state is globally asymptotically stable. The conditions imply that the steady states are always globally asymptotically stable for Holling type II functional response or for a saturation response.