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.
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.
Department of Biomedical Engineering, Science and Research Branch, Islamic Azad University, Tehran, Iran.
Gelayol Nazari
GN
Golpayegani
Medical Physics and Biomedical Engineering Department, School of Medicine, Tehran University of Medical Science, Tehran, Iran.|Research Center for Biomedical Technologies and Robotics, Tehran University of Medical Sciences, Tehran, Iran.
Amir Homayoun
AH
Jafari
Department of Biomedical Engineering, Science and Research Branch, Islamic Azad University, Tehran, Iran.
Nader Jafarnia
NJ
Dabanloo
D044966:Anti-Retroviral Agents / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use*; D000914:Antibodies, Viral / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D003198:Computer Simulation; D004279:DNA, Viral; D024882:Drug Resistance, Viral / Q000276:immunology; D004359:Drug Therapy, Combination; D015658:HIV Infections / Q000188:drug therapy* / Q000235:genetics / Q000276:immunology*; D006801:Humans; D008954:Models, Biological; D009154:Mutation / Q000276:immunology; D013997:Time Factors; D019562:Viral Load / Q000187:drug effects / Q000502:physiology
D044966:Anti-Retroviral Agents; D000914:Antibodies, Viral; D004279:DNA, Viral
%Antiretroviral therapy; %cellular automata model; %immune system; HIV infection