Search

In this study, we apply optimal control theory to an immuno-epidemiological model of HIV and opioid epidemics. For the multi-scale model, we used four controls: treating the opioid use, reducing HIV risk behaviour among opioid users, entry inhibiting antiviral therapy, and antiviral therapy which blocks the viral production. Two population-level controls are combined with two within-host-level controls. We prove the existence and uniqueness of an optimal control quadruple. Comparing the two population-level controls, we find that reducing the HIV risk of opioid users has a stronger impact on the population who is both HIV-infected and opioid-dependent than treating the opioid disorder. The within-host-level antiviral treatment has an effect not only on the co-affected population but also on the HIV-only infected population. Our findings suggest that the most effective strategy for managing the HIV and opioid epidemics is combining all controls at both within-host and between-host scales. [ABSTRACT FROM AUTHOR]

This study examines the interactions between healthy target cells, infected target cells, virus particles, and immune cells within an HIV model. The model exhibits two equilibrium points: an infection-free equilibrium and an infection equilibrium. Stability analysis shows that the infection-free equilibrium is locally asymptotically stable when R 0 < 1 . Further, it is unstable when R 0 > 1 . The infection equilibrium is locally asymptotically stable when R 0 > 1 . The structural and practical identifiabilities of the within-host model for HIV infection dynamics were investigated using differential algebra techniques and Monte Carlo simulations. The HIV model was structurally identifiable by observing the total uninfected and infected target cells, immune cells, and viral load. Monte Carlo simulations assessed the practical identifiability of parameters. The production rate of target cells (λ) , the death rate of healthy target cells (d) , the death rate of infected target cells (δ) , and the viral production rate by infected cells (π) were practically identifiable. The rate of infection of target cells by the virus (β) , the death rate of infected cells by immune cells (Ψ) , and antigen-driven proliferation rate of immune cells (b) were not practically identifiable. Practical identifiability was constrained by the noise and sparsity of the data. Analysis shows that increasing the frequency of data collection can significantly improve the identifiability of all parameters. This highlights the importance of optimal data sampling in HIV clinical studies, as it determines the best time points, frequency, and the number of sample points required to accurately capture the dynamics of the HIV infection within a host. [ABSTRACT FROM AUTHOR]

In this paper, we use a previously developed measles model to forecast measles in Turkey for the period 1970–2021. We study the structural identifiability of the model both by hand and using software. By hand, we assume the prevalence and the total population size are given. Using software, we assume the incidence and the total population size are given. The model is structurally identifiable if one of the three parameters is fixed. We notice that Turkey has a significant change in time of the immigration rate and vaccination proportions, so we assume these two quantities are time-dependent. We fit the nonautonomous model to the measles incidences in Turkey for 1970–2021. We perform practical identifiability of the fitted model, and find that all parameters but one are practically identifiable. When fixing the unidentifiable parameter to a value derived from additional data, we obtain that all parameters are practically identifiable. [ABSTRACT FROM AUTHOR]

We used a previously introduced HIV within-host model with sensitive and resistant strains and validated it with two data sets. The first data set is from a clinical study that investigated multi-drug treatments and measured the total CD4+ cell count and viral load. All nine patients in this data set experienced virologic failure. The second data set includes a unique patient who was treated with a unique drug and for whom both the sensitive and resistant strains were measured as well as the CD4+ cells. We studied the structural identifiability of the model with respect to each data set. With respect to the first data set, the model was structurally identifiable when the viral production rate of the sensitive strain was fixed and distinct from the viral production rate of the resistant strain. With respect to the second data set, the model was always structurally identifiable. We fit the model to the first data set using nonlinear mixed effect modeling in Monolix and estimated the population-level parameters. We inferred that the average time to emergence of a resistant strain is 844 days after treatment starts. We fit the model to the second data set and found out that the all the parameters except the mutation rate were practically identifiable. [ABSTRACT FROM AUTHOR]

Human immunodeficiency virus (HIV) infection is a major public health concern with 1.2 million people living with HIV in the United States. The role of nutrition in general, and albumin/globulin in particular in HIV progression has long been recognized. However, no mathematical models exist to describe the interplay between HIV and albumin/globulin. In this paper, we present a family of models of HIV and the two protein components albumin and globulin. We use albumin, globulin, viral load and target cell data from simian immunodeficiency virus (SIV)-infected monkeys to perform model selection on the family of models. We discover that the simplest model accurately and uniquely describes the data. The selection of the simplest model leads to the observation that albumin and globulin do not impact the infection rate of target cells by the virus and the clearance of the infected target cells by the immune system. Moreover, the recruitment of target cells and immune cells are modeled independently of globulin in the selected model. Mathematical analysis of the selected model reveals that the model has an infection-free equilibrium and a unique infected equilibrium when the immunological reproduction number is above one. The infection-free equilibrium is locally stable when the immunological reproduction number is below one, and unstable when the immunological reproduction number is greater than one. The infection equilibrium is locally stable whenever it exists. To determine the parameters of the best fitted model we perform structural and practical identifiability analysis. The structural identifiability analysis reveals that the model is identifiable when the immune cell infection rate is fixed at a value obtained from the literature. Practical identifiability reveals that only seven of the sixteen parameters are practically identifiable with the given data. Practical identifiability of parameters performed with synthetic data sampled a lot more frequently reveals that only two parameters are practically unidentifiable. We conclude that experiments that will improve the quality of the data can help improve the parameter estimates and lead to better understanding of the interplay of HIV and albumin-globulin metabolism. [ABSTRACT FROM AUTHOR]