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.
We formulate a dynamic mathematical model that describes the interaction of the immune system with the human immunodeficiency virus (HIV) and that permits drug "cocktail" therapies. We derive HIV therapeutic strategies by formulating and analyzing an optimal control problem using two types of dynamic treatments representing reverse transcriptase inhibitors (RTIs) and protease inhibitors (PIs). Continuous optimal therapies are found by solving the corresponding optimality systems. In addition, using ideas from dynamic programming, we formulate and derive suboptimal structured treatment interruptions (STI) in antiviral therapy that include drug-free periods of immune-mediated control of HIV. Our numerical results support a scenario in which STI therapies can lead to long term control of HIV by the immune response system after discontinuation of therapy.
In this paper we study the dynamics of a vector-transmitted disease using two deterministic models. First, we look at time dependent prevention and treatment efforts, where optimal control theory is applied. Using analytical and numerical techniques, it is shown that there are cost effective control efforts for treatment of hosts and prevention of host-vector contacts. Then, we considered the autonomous counter part of the mode and we established global stability results based on the reproductive number. The model is applied to study the effects of prevention and treatment controls on a malaria disease while keeping the implementation cost at a minimum. Numerical results indicate the effects of the two controls (prevention and treatment) in lowering exposed and infected members of each of the populations. The study also highlights the effects of some model parameters on the results.
We consider optimal dynamic multidrug therapies for human immunodeficiency virus (HIV) type 1 infection. In this context, we describe an optimal tracking problem attempting to drive the states of the system to a stationary state in which the viral load is low and the immune response is strong. We consider optimal feedback control with full-state as well as with partial-state measurements. In the case of partialstate measurement, a state estimator is constructed based on viral load and T-cell count measurements. We demonstrate by numerical simulations that by anticipation of and response to the disease progression, the dynamic multidrug strategy reduces the viral load, increases the CD4+ T-cell count and improves the immune response.
Since the 1980s, there has been a worldwide re-emergence of vector-borne diseases including Malaria, Dengue, Yellow fever or, more recently, chikungunya. These viruses are arthropod-borne viruses (arboviruses) transmitted by arthropods like mosquitoes of Aedes genus. The nature of these arboviruses is complex since it conjugates human, environmental, biological and geographical factors. Recent researchs have suggested, in particular during the Reunion Island epidemic in 2006, that the transmission by Aedes albopictus (an Aedes genus specie) has been facilitated by genetic mutations of the virus and the vector capacity to adapt to non tropical regions. In this paper we formulate an optimal control problem, based on biological observations. Three main efforts are considered in order to limit the virus transmission. Indeed, there is no vaccine nor specific treatment against chikungunya, that is why the main measures to limit the impact of such epidemic have to be considered. Therefore, we look at time dependent breeding sites destruction, prevention and treatment efforts, for which optimal control theory is applied. Using analytical and numerical techniques, it is shown that there exist cost effective control efforts.
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