Transmission dynamics of HIV/AIDS with screening and non-linear incidence

This paper examines the transmission dynamics of HIV/AIDS with screening using non-linear incidence. A nonlinear mathematical model for the problem is proposed and analysed qualitatively using the stability theory of the differential equations. The results show that the disease free equilibrium is locally stable at threshold parameter less than unity and unstable at threshold parameter greater than unity. Globally, the disease free equilibrium is not stable due existence of forward bifurcation at threshold parameter equal to unity. However numerical results suggest that screening of unaware infectives has the effect of reducing the transmission dynamics of HIV/AIDS. Also, the effect of non-linear incidence parameters showed that transmission dynamics of HIV/AIDS will be lowered when infectives after becoming aware of their infection, do not take part in sexual interaction or use preventive measures to prevent the spreading of the infection. Numerical simulation of the model is implemented to investigate the sensitivity of certain key parameters on the transmission dynamics of HIV/AIDS with screening using non-linear incidence.Keywords: HIV/AIDS, Screening, Non-linear incidence, Reproduction number, Stabilit

Occurrence of HIV eradication for preexposure prophylaxis treatment with a deterministic HIV model

The authors examine the human immunodeficiency virus (HIV) eradication in this study using a mathematical model and analyse the occurrence of virus eradication during the early stage of infection. To this end they use a deterministic HIV-infection model, modify it to describe the pharmacological dynamics of antiretroviral HIV drugs, and consider the clinical experimental results of preexposure prophylaxis HIV treatment. They also use numerical simulation to model the experimental scenario, thereby supporting the clinical results with a model-based explanation. The study results indicate that the protocol employed in the experiment can eradicate HIV in infected patients at the early stage of the infection

Multiobjective optimization to a TB-HIV/AIDS coinfection optimal control problem

We consider a recent coinfection model for Tuberculosis (TB), Human Immunodeficiency Virus (HIV) infection and Acquired Immunodeficiency Syndrome (AIDS) proposed in [Discrete Contin. Dyn. Syst. 35 (2015), no. 9, 4639--4663]. We introduce and analyze a multiobjective formulation of an optimal control problem, where the two conflicting objectives are: minimization of the number of HIV infected individuals with AIDS clinical symptoms and coinfected with AIDS and active TB; and costs related to prevention and treatment of HIV and/or TB measures. The proposed approach eliminates some limitations of previous works. The results of the numerical study provide comprehensive insights about the optimal treatment policies and the population dynamics resulting from their implementation. Some nonintuitive conclusions are drawn. Overall, the simulation results demonstrate the usefulness and validity of the proposed approach.Comment: This is a preprint of a paper whose final and definite form is with 'Computational and Applied Mathematics', ISSN 0101-8205 (print), ISSN 1807-0302 (electronic). Submitted 04-Feb-2016; revised 11-June-2016 and 02-Sept-2016; accepted for publication 15-March-201

Initiation of HIV therapy

In this paper, we numerically show that the dynamics of the HIV system is sensitive to both the initial condition and the system parameters. These phenomena imply that the system is chaotic and exhibits a bifurcation behavior. To control the system, we propose to initiate an HIV therapy based on both the concentration of the HIV-1 viral load and the ratio of the CD4 lymphocyte population to the CD8 lymphocyte population. If the concentration of the HIV-1 viral load is higher than a threshold, then the first type of therapy will be applied. If the concentration of the HIV-1 viral load is lower than or equal to the threshold and the ratio of the CD4 lymphocyte population to the CD8 lymphocyte population is greater than another threshold, then the second type of therapy will be applied. Otherwise, no therapy will be applied. The advantages of the proposed control strategy are that the therapy can be stopped under certain conditions, while the state variables of the overall system is asymptotically stable with fast convergent rate, the concentration of the controlled HIV-1 viral load is monotonic decreasing, as well as the positivity constraint of the system states and that of the dose concentration is guaranteed to be satisfied. Computer numerical simulation results are presented for an illustration

Sieve estimation of constant and time-varying coefficients in nonlinear ordinary differential equation models by considering both numerical error and measurement error

This article considers estimation of constant and time-varying coefficients in nonlinear ordinary differential equation (ODE) models where analytic closed-form solutions are not available. The numerical solution-based nonlinear least squares (NLS) estimator is investigated in this study. A numerical algorithm such as the Runge--Kutta method is used to approximate the ODE solution. The asymptotic properties are established for the proposed estimators considering both numerical error and measurement error. The B-spline is used to approximate the time-varying coefficients, and the corresponding asymptotic theories in this case are investigated under the framework of the sieve approach. Our results show that if the maximum step size of the $p$-order numerical algorithm goes to zero at a rate faster than $n^{-1/(p\wedge4)}$, the numerical error is negligible compared to the measurement error. This result provides a theoretical guidance in selection of the step size for numerical evaluations of ODEs. Moreover, we have shown that the numerical solution-based NLS estimator and the sieve NLS estimator are strongly consistent. The sieve estimator of constant parameters is asymptotically normal with the same asymptotic co-variance as that of the case where the true ODE solution is exactly known, while the estimator of the time-varying parameter has the optimal convergence rate under some regularity conditions. The theoretical results are also developed for the case when the step size of the ODE numerical solver does not go to zero fast enough or the numerical error is comparable to the measurement error. We illustrate our approach with both simulation studies and clinical data on HIV viral dynamics.Comment: Published in at http://dx.doi.org/10.1214/09-AOS784 the Annals of Statistics (http://www.imstat.org/aos/) by the Institute of Mathematical Statistics (http://www.imstat.org

Estimation of constant and time-varying dynamic parameters of HIV infection in a nonlinear differential equation model

Modeling viral dynamics in HIV/AIDS studies has resulted in a deep understanding of pathogenesis of HIV infection from which novel antiviral treatment guidance and strategies have been derived. Viral dynamics models based on nonlinear differential equations have been proposed and well developed over the past few decades. However, it is quite challenging to use experimental or clinical data to estimate the unknown parameters (both constant and time-varying parameters) in complex nonlinear differential equation models. Therefore, investigators usually fix some parameter values, from the literature or by experience, to obtain only parameter estimates of interest from clinical or experimental data. However, when such prior information is not available, it is desirable to determine all the parameter estimates from data. In this paper we intend to combine the newly developed approaches, a multi-stage smoothing-based (MSSB) method and the spline-enhanced nonlinear least squares (SNLS) approach, to estimate all HIV viral dynamic parameters in a nonlinear differential equation model. In particular, to the best of our knowledge, this is the first attempt to propose a comparatively thorough procedure, accounting for both efficiency and accuracy, to rigorously estimate all key kinetic parameters in a nonlinear differential equation model of HIV dynamics from clinical data. These parameters include the proliferation rate and death rate of uninfected HIV-targeted cells, the average number of virions produced by an infected cell, and the infection rate which is related to the antiviral treatment effect and is time-varying. To validate the estimation methods, we verified the identifiability of the HIV viral dynamic model and performed simulation studies.Comment: Published in at http://dx.doi.org/10.1214/09-AOAS290 the Annals of Applied Statistics (http://www.imstat.org/aoas/) by the Institute of Mathematical Statistics (http://www.imstat.org

Mathematical modelling of internal HIV dynamics

We study a mathematical model for the viral dynamics of HIV in an infected individual in the presence of HAART. The paper starts with a literature review and then formulates the basic mathematical model. An expression for R0, the basic reproduction number of the virus under steady state application of HAART, is derived followed by an equilibrium and stability analysis. There is always a disease-free equilibrium (DFE) which is globally asymptotically stable for R0 1 then some simulations will die out whereas others will not. Stochastic simulations suggest that if R0 > 1 those which do not die out approach a stochastic quasi-equilibrium consisting of random uctuations about the non-trivial deterministic equilibrium levels, but the amplitude of these uctuations is so small that practically the system is at the non-trivial equilibrium. A brief discussion concludes the paper

A Stochastic Model of Latently Infected Cell Reactivation and Viral Blip Generation in Treated HIV Patients

Motivated by viral persistence in HIV+ patients on long-term anti-retroviral treatment (ART), we present a stochastic model of HIV viral dynamics in the blood stream. We consider the hypothesis that the residual viremia in patients on ART can be explained principally by the activation of cells latently infected by HIV before the initiation of ART and that viral blips (clinically-observed short periods of detectable viral load) represent large deviations from the mean. We model the system as a continuous-time, multi-type branching process. Deriving equations for the probability generating function we use a novel numerical approach to extract the probability distributions for latent reservoir sizes and viral loads. We find that latent reservoir extinction-time distributions underscore the importance of considering reservoir dynamics beyond simply the half-life. We calculate blip amplitudes and frequencies by computing complete viral load probability distributions, and study the duration of viral blips via direct numerical simulation. We find that our model qualitatively reproduces short small-amplitude blips detected in clinical studies of treated HIV infection. Stochastic models of this type provide insight into treatment-outcome variability that cannot be found from deterministic models

Saturation Effects and the Concurrency Hypothesis: Insights from an Analytic Model

Sexual partnerships that overlap in time (concurrent relationships) may play a significant role in the HIV epidemic, but the precise effect is unclear. We derive edge-based compartmental models of disease spread in idealized dynamic populations with and without concurrency to allow for an investigation of its effects. Our models assume that partnerships change in time and individuals enter and leave the at-risk population. Infected individuals transmit at a constant per-partnership rate to their susceptible partners. In our idealized populations we find regions of parameter space where the existence of concurrent partnerships leads to substantially faster growth and higher equilibrium levels, but also regions in which the existence of concurrent partnerships has very little impact on the growth or the equilibrium. Additionally we find mixed regimes in which concurrency significantly increases the early growth, but has little effect on the ultimate equilibrium level. Guided by model predictions, we discuss general conditions under which concurrent relationships would be expected to have large or small effects in real-world settings. Our observation that the impact of concurrency saturates suggests that concurrency-reducing interventions may be most effective in populations with low to moderate concurrency

Spread and Control of the Dynamics of HIV/AIDS-TB Co-infection in Ethiopia: A Mathematical Model Analysis

In this work we considered a nonlinear deterministic dynamical system to study the dynamics of HIV/AIDS-TB co-infection in Ethiopia. We found the system exhibit disease free equilibrium point and endemic equilibrium point. For the reproduction number  the disease-free equilibrium point is locally asymptomatically stable and the endemic equilibrium point is locally asymptomatically unstable. We calculate basic reproduction number of the HIV/AIDS-TB co-infection dynamical system which depends on six parameters. Using real data collected from different sectors in Ethiopia we found that the numerical value of the basic reproduction number is. This shows that HIV/AIDS–TB co-infection spread in the society. Using sensitive analysis, we identify the most influential control parameter is the HIV/AIDS-TB co-infection transmission rate. The HIV/AIDS-TB co-infection transmission rate which numerical value to be 0.021. But the real value of is 0.74, to be 0.74 in to 0.021 by fixing the number of contacts for HIV/AIDS-TB co-infection we decrease the effective number of contacts for HIV/AIDS-TB co-infection 74 to 21.  We also perform numerical simulation based on real data collected from different health sectors in Ethiopia. &nbsp