Modeling the Virus-Immune System Interactions in the Peripheral Bloodstream of Hiv Infected Individuals Using a Cellular Automata Model With Considering the Effects of Antiretroviral Therapy Publisher Pubmed



Golpayegani GN¹ ; Jafari AH^{2, 3} ; Dabanloo NJ¹
Source: Technology and Health Care Published:2017

Abstract

BACKGROUND: According to the World Health Organization, by the end of last year, about 37 million people throughout the world were diagnosed with AIDS and millions of people die each year from this disease. OBJECTIVE: To develop an appropriate model which depicts the mechanism of the dynamics involved in the interactions between HIV and immune system in peripheral bloodstream of HIV infected individuals by considering the phenomena of virus mutation and taking into account the role of latently infected cells in speared of infection and considering the effects of antiretroviral drugs and occurrence of drug resistance in our model in order to assess the results obtained from applying different therapeutic methods. METHODS: Two-dimensional CA model with Moor neighboring was developed. Various agents which they were referring to peripheral bloodstream particles of HIV infected individuals were defined. Then the biological rules were extracted from both expert knowledge and the authoritative articles. The extracted rules were applied for updating the states of these agents. The effects of using antiretroviral drug treatment were considered by applying drug's effectiveness of both of protease and reverse transcriptase inhibitors as two separate inputs of model. RESULTS: Time evolution curves of concentrations of defined agents were shown as our results. In case of considering no treatment, our results showed that concentrations of healthy CD4+T cells reached the threshold of AIDS after a bout 250 weeks. By applying monotherapy method, the concentrations of these cells remained on the threshold of AIDS for a long time and applying combined antiretroviral therapy (cART) method leaded to increase the concentration of these cells 20% upper than threshold of AIDS. Also, by applying monotherapy and cART compared with no treatment, the concentrations of infected CD4+T cells 10% and 40% decreased further, respectively and for the level of viral load, leads to a reduction of almost 55% and 90%, respectively. Belated treatment, comparison with early treatment, caused almost 10% reduce (increase) in steady state concentrations of healthy (infected) cells. CONCLUSIONS: Our proposed CA model reproduced three stages of the disease in the known history of HIV dynamics named primary infection response, clinical latency and onset of AIDS. In phase of considering no treatment, our results showed good compatibility with reference HIV curve. In the phase of applying different types of therapeutic methods, our results showed that, RTI and PI monotherapy methods have more favorable effects on the concentrations of healthy and infected cells, respectively. However, by applying cART, the best results were obtained. It was also found that the amount of effectiveness of drugs has a direct relation with quality of results and early treatment leads to better results. By comparing our results with available clinical data, our proposed CA model was validated. © 2017 IOS Press and the authors. All rights reserved.