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The AIDS is a chronic disease and the researchers still exert their high efforts to reach the cure of HIV infection. The most common treatment is the antiretroviral therapy (cART) and the virus can be more effected if the patients stop using cART. The other problem is that the CD8+ T cells might be exhausted by persistent immune activation by cART. This paper introduces fractional-order into a mathematical model of HIV infection combining with stem cell therapy and control the infection by the immune system cells (CD8+ T cells). The paper introduced the numerical solutions for the mathematical model. The results show that the stem cell therapy with the activation of immune system cells might causes the cure for a HIV patient. This results are consistent with medical studies. Also, we proposed the effect of the fractional order (α) on the figures of the components. [ABSTRACT FROM AUTHOR]

In several publications, the dynamical system of HIV and HTLV mono-infections taking into account diffusion, as well as latently infected cells in cellular transmission has been mathematically analyzed. However, no work has been conducted on HTLV/HIV co-infection dynamics taking both factors into consideration. In this paper, a partial differential equations (PDEs) model of HTLV/HIV dual infection was developed and analyzed, considering the cells' and viruses' spatial mobility. CD 4 + T cells are the primary target of both HTLV and HIV. For HIV, there are three routes of transmission: free-to-cell (FTC), latent infected-to-cell (ITC), and active ITC. In contrast, HTLV transmits horizontally through ITC contact and vertically through the mitosis of active HTLV-infected cells. In the beginning, the well-posedness of the model was investigated by proving the existence of global solutions and the boundedness. Eight threshold parameters that determine the existence and stability of the eight equilibria of the model were obtained. Lyapunov functions together with the Lyapunov–LaSalle asymptotic stability theorem were used to investigate the global stability of all equilibria. Finally, the theoretical results were verified utilizing numerical simulations. [ABSTRACT FROM AUTHOR]

Latently infected CD 4 + T cells represent one of the major obstacles to HIV eradication even after receiving prolonged highly active anti-retroviral therapy (HAART). Long-term use of HAART causes the emergence of drug-resistant virus which is then involved in HIV transmission. In this paper, we develop mathematical HIV models with staged disease progression by incorporating entry inhibitor and latently infected cells. We find that entry inhibitor has the same effect as protease inhibitor on the model dynamics and therefore would benefit HIV patients who developed resistance to many of current anti-HIV medications. Numerical simulations illustrate the theoretical results and show that the virus and latently infected cells reach an infected steady state in the absence of treatment and are eliminated under treatment whereas the model including homeostatic proliferation of latently infected cells maintains the virus at low level during suppressive treatment. Therefore, complete cure of HIV needs complete eradication of latent reservoirs. [ABSTRACT FROM AUTHOR]

The human immunodeficiency virus (HIV) interacts with the immune cells within the human body, where the environment is uncertain and noisy. Stochastic models can successfully encapsulate the effect of such a noisy environment compared to their deterministic counterparts. The human immune system is complex but well-coordinated with various immune cells like C D 4 + T cells, dendritic cells, and cytotoxic T-lymphocyte (CTL) cells, among many others. The CTL can kill the antigenic cells after its recognition. However, the efficacy of CTL in removing the infected C D 4 + T cells is progressively compromised in HIV-infected individuals. This paper considers a noise-induced HIV-immune cell interaction model with immune impairment. A multiplicative white noise is introduced in the infection rate parameter to represent the fluctuations around the average value of the rate parameter as a causative effect of the noise. We analyzed the deterministic and stochastic models and prescribed sufficient conditions for infection eradication and persistence. It is determined under what parametric restrictions the asymptotic solutions of the noise-induced system will be a limiting case of the deterministic solutions. Simulation results revealed that the solutions of the deterministic system either converge to a CTL-dominated interior equilibrium or a CTL-free immunodeficient equilibrium, depending on the initial values of the system. Stochastic analysis divulged that higher noise might be helpful in the infection removal process. The extinction time of infected C D 4 + T cells for some fixed immune impairment gradually decreases with increasing noise intensity and follows the power law. [ABSTRACT FROM AUTHOR]

In this paper, we formulate a within‐host dynamics model for HIV/HTLV‐I co‐infection under the influence of cytotoxic T lymphocytes (CTLs). The model incorporates silent HIV‐infected CD4+T cells and silent HTLV‐infected CD4+T cells. The model includes two routes of HIV transmission, virus to cell (VTC) and cell to cell (CTC). It also incorporates two modes of HTLV‐I transmission, horizontal transmission via direct CTC contact and vertical transmission through mitotic division of Tax‐expressing HTLV‐infected cells. The model takes into account five types of distributed‐time delays. We analyze the model by proving the nonnegativity and boundedness of the solutions, calculating all possible equilibria, deriving a set of key threshold parameters, and proving the global stability of all equilibria. The global asymptotic stability of all equilibria is established by utilizing Lyapunov function and LaSalle's invariance principle. We present numerical simulations to justify the applicability and effectiveness of the theoretical results. In addition, we discuss the effect of HTLV‐I infection on the HIV dynamics and vice versa. [ABSTRACT FROM AUTHOR]

In this paper, the Pseudospectral Legendre (PL) method is presented to approximate the solution of the HIV infection model of CD4+T cells. The method is based on the Lagrangian interpo- lation and the zeros of Legendre polynomial. Using the proposed method, the given system of three differential equations is converted into a system of algebraic equations. By solving the system of the algebraic equations, the unknown coefficients are computed and then the approximate solutions are obtained. The main aim of this paper is to demonstrate the PL method, and a comparison is made with the existing methods in the literature. [ABSTRACT FROM AUTHOR]

In this paper, we introduce a Galerkin method based on Legendre multiwavelet functions to obtain approximate solutions of a fractional model for HIV infection of CD4+T cells corresponding to a class of systems of nonlinear fractional differential equations. The method converts the model problem into a system of nonlinear algebraic equations. A numerical example is included to demonstrate the validity and applicability of the technique and the results are compared with those obtained by existing methods. [ABSTRACT FROM AUTHOR]

In this paper, a model of HIV infection taking into account cell-free and cell-to-cell transmissions is investigated under latency. The viral production rate of infectious CD4 T cells and the activation rate of latently infected CD4 T cells play a major role in the evolution of the disease. A system of nonlinear differential equations is derived to capture the dynamics and systematically analyzed thanks to the spectral theory of dynamical systems and a Routh-Hurwitz criterion. In particular, numerical simulations will be performed in order to extract the critical epidemiological features of the solution. [ABSTRACT FROM AUTHOR]

HIV infection is one of the most serious causes of death throughout the world. CD4+ T cells which play an important role in immune protection, are the primary targets for HIV infection. The hallmark of HIV infection is the progressive loss in population of CD4+ T cells. However, the pathway causing this slow T cell decline is poorly understood [16]. This paper studies a discontinuous mathematical model for HIV-1 infection, to investigate the effect of pyroptosis on the disease. For this purpose, we use the theory of discontinuous dynamical systems. In this way, we can better analyze the dynamical behavior of the HIV-1 system. Especially, considering the dynamics of the system on its discontinuity boundary enables us to obtain more comprehensive results rather than the previous researches. A stability region for the system, corresponding to its equilibria on the discontinuity boundary, will be determined. In such a parametric region, the trajectories of the system will be trapped on the discontinuity manifold forever. It is also shown that in the obtained stability region, the disease can lead to a steady state in which the population of uninfected T cells and viruses will preserve at a constant level of cytokines. This means that the pyroptosis will be restricted and the disease cannot progress for a long time. Some numerical simulations based on clinical and experimental data are given which are in good agreement with our theoretical results. [ABSTRACT FROM AUTHOR]

HIV preferentially infects activated CD4+ T cells. Current antiretroviral therapy cannot eradicate the virus. Viral infection of other cells such as macrophages may contribute to viral persistence during antiretroviral therapy. In addition to cell-free virus infection, macrophages can also get infected when engulfing infected CD4+ T cells as innate immune sentinels. How macrophages affect the dynamics of HIV infection remains unclear. In this paper, we develop an HIV model that includes the infection of CD4+ T cells and macrophages via cell-free virus infection and cell-to-cell viral transmission. We derive the basic reproduction number and obtain the local and global stability of the steady states. Sensitivity and viral dynamics simulations show that even when the infection of CD4+ T cells is completely blocked by therapy, virus can still persist and the steady-state viral load is not sensitive to the change of treatment efficacy. Analysis of the relative contributions to viral replication shows that cell-free virus infection leads to the majority of macrophage infection. Viral transmission from infected CD4+ T cells to macrophages during engulfment accounts for a small fraction of the macrophage infection and has a negligible effect on the total viral production. These results suggest that macrophage infection can be a source contributing to HIV persistence during suppressive therapy. Improving drug efficacies in heterogeneous target cells is crucial for achieving HIV eradication in infected individuals. [ABSTRACT FROM AUTHOR]

In this paper, a mathematical model is formulated to investigate the dynamics of HIV infection. The model incorporates two routes of infection (namely cell-to-cell transmission and virus-to-cell infection), two types of adaptive immune responses (i.e., cellular and antibody immune response) and two intracellular delays (viz., the eclipse phase and virus production period). By constructing Lyapunov functionals, we show that the global dynamics of the model can be explicitly determined by five reproduction numbers. Using the uncertainty and sensitivity analyses, we obtain the mean values and standard deviation of the five reproduction numbers and find that the reproduction numbers are most sensitive to the death rate of infected cells, viral clearance rate and immune parameters. We further compare four related HIV models and show that cell-to-cell transmission, immune responses and time delays can substantially affect the dynamical behavior of the system. Specifically, cell-to-cell transmission increases the concentration of infected cells. Inclusion of cytotoxic T lymphocyte and virus production delay can significantly reduce the viral load and infected cell concentration, and generate a higher level of uninfected CD4+ T cells. The analytical and numerical results may help to improve the understanding of HIV dynamics. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

In this paper, the human immunodeficiency virus (HIV) infection model of CDT-cells is considered. In order to numerically solve the model problem, an operational method is proposed. For that purpose, we construct the operational matrix of integration for bases of Taylor polynomials. Then, by using this matrix operation and approximation by polynomials, the HIV infection problem is transformed into a system of algebraic equations, whose roots are used to determine the approximate solutions. An important feature of the method is that it does not require collocation points. In addition, an error estimation technique is presented. We apply the present method to two numerical examples and compare our results with other methods. [ABSTRACT FROM AUTHOR]

Estimating the time since infection (TI) in newly diagnosed HIV-1 patients is challenging, but important to understand the epidemiology of the infection. Here we explore the utility of virus diversity estimated by next-generation sequencing (NGS) as novel biomarker by using a recent genome-wide longitudinal dataset obtained from 11 untreated HIV-1-infected patients with known dates of infection. The results were validated on a second dataset from 31 patients. Virus diversity increased linearly with time, particularly at 3rd codon positions, with little inter-patient variation. The precision of the TI estimate improved with increasing sequencing depth, showing that diversity in NGS data yields superior estimates to the number of ambiguous sites in Sanger sequences, which is one of the alternative biomarkers. The full advantage of deep NGS was utilized with continuous diversity measures such as average pairwise distance or site entropy, rather than the fraction of polymorphic sites. The precision depended on the genomic region and codon position and was highest when 3rd codon positions in the entire pol gene were used. For these data, TI estimates had a mean absolute error of around 1 year. The error increased only slightly from around 0.6 years at a TI of 6 months to around 1.1 years at 6 years. Our results show that virus diversity determined by NGS can be used to estimate time since HIV-1 infection many years after the infection, in contrast to most alternative biomarkers. We provide the regression coefficients as well as web tool for TI estimation. unfortunately, they only distinguish between recent and long-term infections (concentration of HIV-1-specific antibodies) or are imprecise (immune status as measured by levels of CD4+ T-lymphocytes and viral sequence diversity measured by polymorphisms in Sanger sequences). In this paper, we show that recent advances in sequencing technologies, i.e. the development of next generation sequencing, enable significantly more precise determination of the time since HIV-1 infection, even many years after the infection event. This is a significant advance which could translate into more effective HIV-1 prevention [ABSTRACT FROM AUTHOR]

In this paper, we study the HIV infection model based on fractional derivative with particular focus on the degree of T-cell depletion that can be caused by viral cytopathicity. The arbitrary order of the fractional derivatives gives an additional degree of freedom to fit more realistic levels of CD4 cell depletion seen in many AIDS patients. We propose an implicit numerical scheme for the fractional-order HIV model using a finite difference approximation of the Caputo derivative. The fractional system has two equilibrium points, namely the uninfected equilibrium point and the infected equilibrium point. We investigate the stability of both equilibrium points. Further we examine the dynamical behavior of the system by finding a bifurcation point based on the viral death rate and the number of new virions produced by infected CD4 T-cells to investigate the influence of the fractional derivative on the HIV dynamics. Finally numerical simulations are carried out to illustrate the analytical results. [ABSTRACT FROM AUTHOR]

In this paper, we construct an HIV infection model which includes latent infection, logistic growth for healthy CD4 T-cells, and antiretroviral therapy. We obtain the global asymptotic stability of the uninfected equilibrium by constructing a Lyapunov function, and we give a sufficient condition for the local asymptotic stability of the infected equilibrium. We also use the latin hypercube sampling technique to identify the key parameters in determining the stability of the infected equilibrium. By numerical simulations, we observe that the model without logistic growth would underestimate the number of infectious virions, while the model without latent infection would overestimate the number of infectious virions. [ABSTRACT FROM AUTHOR]

Abstract: In this paper, we introduce fractional-order into a model of HIV infection of CD4+ T-cells. We show that the model established in this paper possesses non-negative solutions, as desired in any population dynamics. We also carry out a detailed analysis on the stability of equilibrium. Numerical simulations are presented to illustrate the results. [Copyright &y& Elsevier]

In this paper, a bifurcation solution's analysis is proposed for an HIV-1 within the host model around its chronic equilibrium point, this is carried out based on Lyapunov-Schmidt approach. It is shown that the coefficient b, which represents the healthy CD4+ T-cells growth rate, is a bifurcation parameter; this means that the rate of multiplication of healthy cells can have serious effects on the qualitative dynamical properties and structural stability of the infection evolution dynamics. Copyright © 2015 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

During early human immunodeficiency virus (HIV) infection multiple CD8+ T cell responses are elicited almost simultaneously. These responses exert strong selective pressures on different parts of HIV’s genome, and select for mutations that escape recognition and are thus beneficial to the virus. Some studies reveal that the later these escape mutations emerge, the more slowly they go to fixation. This pattern of escape rate decrease(ERD) can arise by distinct mechanisms. In particular, in large populations with high beneficial mutation rates interference among different escape strains –an effect that can emerge in evolution with asexual reproduction and results in delayed fixation times of beneficial mutations compared to sexual reproduction– could significantly impact the escape rates of mutations. In this paper, we investigated how interference between these concurrent escape mutations affects their escape rates in systems with multiple epitopes, and whether it could be a source of the ERD pattern. To address these issues, we developed a multilocus Wright-Fisher model of HIV dynamics with selection, mutation and recombination, serving as a null-model for interference. We also derived an interference-free null model assuming initial neutral evolution before immune response elicitation. We found that interference between several equally selectively advantageous mutations can generate the observed ERD pattern. We also found that the number of loci, as well as recombination rates substantially affect ERD. These effects can be explained by the underexponential decline of escape rates over time. Lastly, we found that the observed ERD pattern in HIV infected individuals is consistent with both independent, interference-free mutations as well as interference effects. Our results confirm that interference effects should be considered when analyzing HIV escape mutations. The challenge in estimating escape rates and mutation-associated selective coefficients posed by interference effects cannot simply be overcome by improved sampling frequencies or sizes. This problem is a consequence of the fundamental shortcomings of current estimation techniques under interference regimes. Hence, accounting for the stochastic nature of competition between mutations demands novel estimation methodologies based on the analysis of HIV strains, rather than mutation frequencies. [ABSTRACT FROM AUTHOR]

Based on some important biological meanings, we propose a class of HIV infection models incorporating both classical cell-free virus diffusion and direct cell-to-cell transmission. According to recent studies, the direct cell-to-cell transfer of HIV is a significantly more efficient mode of retroviral dissemination. In the first part of our analysis, we show that our model possesses non-negative solutions. Then, we derive sufficient conditions for the asymptotic stability of equilibriums. The analytical solutions are verified by simulation results. At the end of the paper, some important conclusions are given. [ABSTRACT FROM AUTHOR]

Statistical analysis of viral dynamics in HIV-1 infected patients undergoing structured treatment interruptions were performed using a novel model that accounts for treatment efficiency as well as total CD8+ T cell counts. A brief review of parameter estimates obtained in other studies is given, pointing to a considerable variation in the estimated values. A Bayesian approach to parameter estimation was used with longitudinal measurements of CD4+ and CD8+ T cell counts and HIV RNA. We describe an estimation procedure which uses spline approximations of CD8+ T cells dynamics. This approach reduces the number of parameters that must be estimated and is especially helpful when the CD8+ T cells growth function has a delayed dependence on the past. Seven important parameters related to HIV-1 in-host dynamics were estimated, most of them treated as global parameters across the group of patients. The estimated values were mainly in keeping with the estimates obtained in other reports, but our paper also introduces the estimates of some new parameters which supplement the current knowledge. The method was also tested on a simulated data set. [ABSTRACT FROM AUTHOR]

This paper proposes an optimal control problem, with the final goal of implementing an optimal treatment protocol which could maximize the uninfected CD4+T cells and minimize the cost of drug, utilizing a system of ordinary differential equations which describes the interaction of the immune system with the human immunodeficiency virus(HIV). The optimal pair of control and trajectories of this nonlinear system with quadratic cost functional is obtained by Fourier series approximation. The method is based upon expanding time varying functions in the nonlinear system as their Fourier series, using the operational matrices for integration and product. The problem is reduced into a set of algebraic equations. [ABSTRACT FROM AUTHOR]

The mass action infection law, the most frequently used transmission process in the theoretical studies of disease dynamics, has been challenged in various ways. Hill type infection rate is supposed to be a better alternative to mass action law. In the first phase of this paper, we study a basic HIV model with Hill type infection rate. In the second phase, we modify our basic model with intracellular delay τ that measures the time between the first effective contact between a virus and a healthy CD4 + T cell and the latter becomes productively infective. Mathematical results like well-posedness, permanence, local stability and global stability of both the delayed and non-delayed systems are studied. It is observed that the endemic equilibrium is locally and globally asymptotically stable if the virus replication factor is greater than a threshold value and unstable otherwise. In the latter case, the disease-free steady state occurs and is proved to be globally asymptotically stable. Our simulation results shed different insights on drug therapy when various perturbations are given to the system. It is shown that multi-blockers drug therapy is more appropriate in the treatment of HIV patients in comparison to any mono-blocker drug therapy. [ABSTRACT FROM AUTHOR]

In this paper, we study the global properties of two mathematical models which describe the interaction of the human immunodeficiency virus (HIV) with two classes of target cells, CD4+ T cells and macrophages. The incidence rate of virus infection is given by the Crowley-Martin functional response. The first model has two types of discrete delays while the second one incorporates two types of distributed delays to describe the time needed for infection of cell and virus replication. The basic reproduction number R0 is identified which completely determines the global dynamics of the models. By constructing suitable Lyapunov functionals, we have proven that if R0 ≤ 1 then the uninfected steady state is globally asymptotically stable (GAS), and if R0 > 1 then the infected steady state exists and it is GAS. [ABSTRACT FROM AUTHOR]

In this paper, we study the global analysis of virus dynamics models with discrete delay and with distributed delay. The models describe the interaction of the HIV with two classes of target cells, CD4+ T cells and macrophages. The incidence rate of virus infection is given by the Beddington-DeAngelis functional response. The models have two types of discrete time delay or distributed delay describing the time needed for infection of cell and virus replication. The basic reproduction number R0 is identified which completely determines the global dynamics of the models. By constructing suitable Lyapunov functionals, we have proven that if R0 ≤ 1 then the uninfected steady state is globally asymptotically stable (GAS), and if R0 > 1 then the infected steady state exists and it is GAS. [ABSTRACT FROM AUTHOR]

Lymphocyte invasion by HIV-1 is a complex, highly regulated process involving many different types of molecules that is prompted by the virus's association with viral receptors located at the cell-surface membrane that culminates in the formation of a fusion pore through which the virus enters the cell. A great deal of work has been done to identify the key actors in the process and determine the regulatory interactions; however, there have been no reports to date of attempts being made to fully understand the system dynamics through a systemic, quantitative modeling approach. In this paper, we introduce a dynamic mathematical model that integrates the available information on the molecular events involved in lymphocyte invasion. Our model shows that moesin activation is induced by virus signaling, while filamin-A is mobilized by the receptor capping. Actin disaggregation from the cap is facilitated by cofilin. Cofilin is inactivated by HIV-1 signaling in activated lymphocytes, while in resting lymphocytes another signal is required to activate cofilin in the later stages in order to accelerate the decay of the aggregated actin as a restriction factor for the viral entry. Furthermore, stopping the activation signaling of moesin is sufficient to liberate the actin filaments from the cap. The model also shows the positive effect of gelsolin on actin capping by means of the nucleation effect. These findings allow us to propose novel approaches in the search for new therapeutic strategies. In particular, gelsolin inhibition is seen as a promising target for preventing HIV-1 entry into lymphocytes, due to its role in facilitating the capping needed for the invasion. Also it is shown that HIV-1 should overcome the cortical actin barrier during early infection and predicts the different susceptibility of CD4+ T cells to be infected in terms of actin cytoskeleton dynamics driven by associated cellular factors. [ABSTRACT FROM AUTHOR]

This paper deals with stability and Hopf bifurcation analyses of a mathematical model of HIV infection of CD4+ T-cells. The model is based on a system of delay differential equations with logistic growth term and antiretroviral treatment with a discrete time delay, which plays a main role in changing the stability of each steady state. By fixing the time delay as a bifurcation parameter, we get a limit cycle bifurcation about the infected steady state. We study the effect of the time delay on the stability of the endemically infected equilibrium. We derive explicit formulae to determine the stability and direction of the limit cycles by using center manifold theory and normal form method. Numerical simulations are presented to illustrate the results. [ABSTRACT FROM AUTHOR]

Abstract: In this paper, we sought to identify the CD4+ T-cell dynamics in the course of HIV infection in response to continuous and intermittent intravenous courses of interleukin-2 (IL-2), the principal cytokine responsible for progression of CD4+ T-lymphocytes from the G1 to the S phase of the cell cycle. Based on multivariate regression models, previous literature has concluded that the increase in survival of CD4+ T-cell appears to be the critical mechanism leading to sustained CD4+ T-cell levels in HIV-infected patients receiving intermittent IL-2 therapy. Underscored by comprehensive mathematical modeling, a major finding of the present work is related to the fact that, rather than due to any increase in survival of CD4+ T-cells, the expressive, selective and sustained CD4+ T-cell expansions following IL-2 administration may be related to the role of IL-2 in modulating the dynamics of Fas-dependent apoptotic pathways, such as activation-induced cell death (AICD) or HIV-specific apoptotic routes triggered by viral proteins. [Copyright &y& Elsevier]

In this paper, we introduce ordinary and delay differential equations to describe the interactions between a malignant tumour and the immune systemin vivoin the presence of human immunodeficiency virus (HIV) infection of CD4+T-cells. In the delay model, we take into account the time lags required by the healthy effector cell components to recognize the pathogens and tumour cells. The models consist of four populations: tumour cells, healthy effector cells (CD4+T-cells), effector cells infected by HIVs and free viral particles. The presence of delay term in the model leads to a notable increase in the complexity of the observed behaviour. We investigate the qualitative behaviour of the models and find the conditions that guarantee the asymptotic stability of the steady states. Numerical simulations are provided to illustrate and extend the theoretical results. The obtained results are consistent with the real phenomena and give a better understanding of cancer immunity and viral oncogenesis. [ABSTRACT FROM PUBLISHER]

Estaquier et al. provide commentary on our paper that elucidated the mechanism by which HIV-1 causes cell death in activated CD4 T lymphocytes. We showed that proviral DNA integration triggers DNA-PK dependent death signaling, leading to p53 phosphorylation and cell demise (Cooper A et al. Nature 498:376-379, 2013). They have raised several hypothetical points that we further clarify here. [ABSTRACT FROM AUTHOR]

In this paper, we investigate global dynamics for an in-host HIV-1 infection model with the long-lived infected cells and four intracellular delays. Our model admits two possible equilibria, an uninfected equilibrium and infected equilibrium depending on the basic reproduction number. We derive that the global dynamics are completely determined by the values of the basic reproduction number: if the basic reproduction number is less than one, the uninfected equilibrium is globally asymptotically stable, and the virus is cleared; if the basic reproduction number is larger than one, then the infection persists, and the infected equilibrium is globally asymptotically stable. [ABSTRACT FROM AUTHOR]

Abstract: For HIV patients, lifelong therapy is generally required to control their viral replication and it is very difficult to effectively eradicate HIV infection from the host. In this paper, using a mathematical model, we show that the stimulation of CD4+ T cells to proliferate in the presence of HIV is one possible factor causing such a difficulty. This is based on the fact that if the proliferation rate is non-negligible, then the model exhibits a backward bifurcation and hysteresis. Fitting to clinical data shows that the CD4+ T-cell proliferation does play an important role for HIV infection under antiretroviral therapy. The model and analysis are then extended to incorporate a bilinear term to account for the loss of free infectious virions during attacking the target cells. Our analysis suggests that, to effectively control HIV infection, antiretroviral therapies should aim at increasing the effectiveness of reverse transcriptase inhibitors and protease inhibitors, discouraging the stimulation of CD4+ T cells, and increasing the loss rate of virus particles when they infect the healthy CD4+ T cells. [Copyright &y& Elsevier]

While antiretroviral drugs can drive HIV to undetectably low levels in the blood, eradication is hindered by the persistence of long-lived, latently infected memory CD4 T cells. Immune activation therapy aims to eliminate this latent reservoir by reactivating these memory cells, exposing them to removal by the immune system and the cytotoxic effects of active infection. In this paper, we develop a mathematical model that investigates the use of immune activation strategies while limiting virus and latent class rebound. Our model considers infection of two memory classes, central and transitional CD4 T cells and the role that general immune activation therapy has on their elimination. Further, we incorporate ways to control viral rebound by blocking activated cell proliferation through anti proliferation therapy. Using the model, we provide insight into the control of latent infection and subsequently into the long term control of HIV infection. [ABSTRACT FROM AUTHOR]

Due to stable incidence and improved survival rates, there are an increasing number of patients living with HIV/AIDS in the USA. Although highly effective, current antiretroviral therapies are associated with a variety of side effects. The role side effects play on health outcomes has not been fully examined. The current study assessed the association of medication side effects with (1) self-assessed health status; (2) work productivity and activity impairment; and (3) healthcare resource utilization. Data were from a cross-sectional patient-reported survey fielded in the USA using a dual methodology of Internet and paper questionnaires. A total of 953 patients living with HIV/AIDS who were currently taking a medication for their condition were included in the analyses. The most frequent side effects reported by patients were fatigue (70.72%), diarrhea (62.96%), insomnia (58.97%), dizziness (52.78%), neuropathy (52.68%), joint pain (52.36%), nausea (51.63%), and abdominal pain (50.37%). The presence of each side effect was associated with reduced self-assessed health status, increased productivity loss, increased activity impairment, and increased healthcare resource use. Controlling for CD4 cell counts in regression modeling did little to diminish the impact of side effects. Although not all side effects were associated with all outcomes, every side effect was associated with worse health status, some measure of increased work productivity loss, and/or some measure of increased healthcare resource use. Patients are living longer with HIV and, therefore, spending a greater length of time on treatment. The results of the current study suggest that many of these patients are experiencing a wide array of side effects from these therapies. These side effects have demonstrated a profound association with self-assessed health, work productivity, and healthcare resource use. Improved management of these side effects or development of treatments with a better side effect profile may have a substantial humanistic and economic benefit. [ABSTRACT FROM AUTHOR]

Abstract: In this paper, we study a delayed six-dimensional human immunodeficiency virus (HIV) model with Cytotoxic T Lymphocytes (CTLs) immune response. Our model describes the interaction of HIV with two target cells: CD4+ T cells and macrophages. We derive that the global asymptotic attractivity of the model is completely determined by the basic reproduction number and the immune reproduction number for the viral infection. By constructing Lyapunov functionals, we have shown that the infection-free equilibrium , the immune-free equilibrium and the chronic-infection equilibrium are globally asymptotically attractive when and , respectively. [Copyright &y& Elsevier]

Today, HIV-infected children who have access to treatment face a chronic rather than a progressive and fatal disease. As a result, new challenges are emerging in the field. Recent lines of evidence outline several factors that can differently affect the ability of the immune system to fully reconstitute and to mount specific immune responses in children receiving HAART. In this paper, we review the underlying mechanisms of immune reconstitution after HAART initiation among vertically HIV-infected children analyzing the possible causes of suboptimal responses. [ABSTRACT FROM AUTHOR]

Background: In highly antiretroviral-experienced patients with a multidrug-resistant human immunodeficiency virus (HIV) infection, recommended regimens should preferentially contain 3 active components, including a ritonavir-boosted protease inhibitor (PI/r). Tipranavir/r (TPV/r), a non-peptidic PI, has been specifically developed for patients resistant to the usual antiretroviral classes including PIs. This paper discusses the role of TPV/r in patients experiencing multiple PI resistance. Methods: Virological, immunological, and safety outcomes were collected between 2003 and 2007 at 7 clinical units. Virus resistance assessment was based on 3 different genotypic tests. The 207 patients evaluated had previously received nucleoside reverse transcriptase inhibitors (NRTIs) and PIs. Results: The main drugs co-administered with TPV/r were 1 or 2 NRTIs associated, in half of the patients, with enfuvirtide. After 12 weeks, viral load was <50 copies/ml in 38% of the patients (44% with enfuvirtide), while median CD4 counts had increased from 150 to 250 cells/mm3. Genotypic testing suggested that most of the patients had viruses susceptible to TPV. Lipid and transaminase levels were slightly modified, and less than 10% of treatment discontinuations were due to gastrointestinal events. Conclusion: A regimen including TPV/r associated with at least 1 active component is a valuable option in highly ARV-experienced patients with multi-resistance to the usual ARV classes including PIs. [ABSTRACT FROM AUTHOR]

In this paper, we introduce fractional-order into a 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. Generalized Euler method (GEM) will be used to find a numerical solution of the HIV-1 infection fractional order model. [ABSTRACT FROM AUTHOR]

Despite a high prevalence of HIV in patients with serious mental health disorders, there is little information in the literature regarding details of their HIV treatment. The objective of this paper is to assess factors associated with the success of HIV therapy in people with schizophrenia, schizoaffective, and bipolar disease. The methods used are retrospective, post-study chart review, and clinician questionnaire at two HIV county clinics. Forty-nine (4.8%) study patients were identified, 51% of whom achieved an undetectable HIV viral load. These patients tended to have less drug use (42% vs. 68%), more ongoing psychiatric visits (70% vs. 58%) and were more apt to take psychiatric medicines (70% vs. 40%) than patients with detectable HIV viral loads. Both groups had many missed appointments. We were surprised to find that many patients were successful with HIV treatment despite substance abuse, uncontrolled psychiatric symptoms, and lack of psychiatric care. Missing clinic appointments had little influence on treatment outcome. [ABSTRACT FROM AUTHOR]

In this paper, an ordinary differential equation model of HIV infection of CD4+ T-cells with saturated reverse function is studied. We prove that if the basic reproduction number R0 < 1, the virus-free equilibrium is locally asymptotically stable. And there will exhibit backward bifurcation when R0 < 1. If R0 > 1, some feasibly sufficient conditions are obtained for the global asymptotic stability of a positive equilibrium of the model by using the theory of competitive systems, compound matrices and stability of periodic orbits. Furthermore, we also obtain the conditions for which the model exists an orbitally asymptotically stable periodic solution. Numerical simulations are presented to illustrate the results. [ABSTRACT FROM AUTHOR]

Abstract: In this paper, we consider an HIV pathogenesis model including cure rate and the full logistic proliferation term of CD4+ T cells in healthy and infected populations. Let be the number of virus released by each productive infected CD4+ T cell. The critical number that ensures the existence of the positive equilibrium is obtained. We further show that if , then there exists a unique uninfected equilibrium point that is locally asymptotically stable. If , then the system is persistent and the only infected steady state is globally asymptotically stable in the feasible region. Numerical simulations are presented to illustrate the obtained main results. Moreover, we find that there exist periodic solutions when the infected steady state is unstable. [Copyright &y& Elsevier]

Abstract: In this paper, the homotopy analysis method (HAM) is investigated to give an approximate solution of a model for HIV infection of CD4+ T-cells. This method allows for the solution of the governing differential equation to be calculated in the form of an infinite series with components which can be easily calculated. The HAM utilizes a simple method to adjust and control the convergence region of the infinite series solution by using an auxiliary parameter. The results obtained are presented, and six terms are sufficient to obtain an approximation solution that is very accurate. [Copyright &y& Elsevier]

The HLA-E protein is one of the most extensively studied MHC class Ib antigens and the least polymorphic one compared to other MHC class I molecules. In the human population there have been reported just ten alleles encoding three different peptides. Only two of these alleles, namely HLA-E*0101 and HLA-E*0103, are widely distributed (around 50% each). The proteins encoded by these alleles differ from each other in one amino acid at position 107. In HLA-E*0101 it is arginine and in HLA-E*0103 it is glycine. The difference between these proteins manifests itself in surface expression levels, affinities to leader peptides and thermal stabilities of their complexes. The HLA-E molecule is a ligand for CD94/NKG2 receptors on NK cells and TCR receptors on NK-CTL (NK-cytotoxic T lymphocyte) cells, so it plays a double role in both innate and adaptive immunity. This paper reviews the knowledge on the role of the HLA-E molecule in the immunological response. Aspects related to polymorphism of the HLA-E gene and the course of several diseases including type I diabetes, ankylosing spondylitis, HCV and HIV infections, nasopharyngeal cancer and recurrent spontaneous abortions, as well as the outcome of hematopoietic stem cell transplantation, are presented and discussed in more detail. [ABSTRACT FROM AUTHOR]

Abstract: In this paper, a multi-step differential transform method (MsDTM) is performed to give approximate and analytical solutions of nonlinear fractional order ordinary differential equation systems such as a model for HIV infection of CD4+ T cells. The numerical solutions obtained from the proposed method indicate that the approach is easy to implement and accurate when applied to systems of fractional differential equations. Some figures are presented to show the reliability and simplicity of the methods. [Copyright &y& Elsevier]

In Vietnam, ARV access has been scaled up since 2005 in high HIV prevalence areas in order to meet increasing demands for HIV treatment. This paper aims to estimate ARV unmet need and its associated socio-demographic characteristics among HIV-positive women in Haiphong, Vietnam. A cross-sectional study using structured questionnaires and CD4 cell count was conducted with 353 HIV-positive women recruited from groups of people living with HIV/AIDS (PLWHA), by snowball technique through member of PLWHA groups and the local AIDS management system (Provincial AIDS Center (PAC)). The percentage of HIV-positive women having an unmet ARV need was estimated to be 40%, particularly high among women who were not registered at PAC. Having an unmet ARV need was associated with not participating in PLWHA groups (OR 6.5; 2.4-17.2) and being younger than 30 years old (OR 2.9; 1.1-7.3). [ABSTRACT FROM AUTHOR]

The major pathway for HIV internalization in CD4+ T cells has been thought to be the direct fusion of virus and cell membranes, because the cell surface is the point of entry of infectious particles. However, the exact contribution of endocytic pathways to the infection of CD4+ T lymphocytes is unknown, and the mechanisms involved in endocytosis of HIV particles are unclear. Recent evidence suggests that endocytosis of cell-free and cell-associated virus particles could lead to effective virus entry and productive infections. Such observations have, in turn, spurred a debate on the relevance of endosomal entry as a mechanism of escape from the immune system and HIV entry inhibitors. In this paper, we review the endocytosis of HIV and discuss its role in HIV infection and pathogenesis. [ABSTRACT FROM AUTHOR]