ИСТИНА

HIV continues to be a major global public health issue, having claimed more than 36 million lives so far. HIV infection results in the progressive deterioration of the immune system, inability of the organism to fend off some infections and other concomitant diseases and concludes with AIDS. Despite the availability of various effective techniques of HIV prevention, diagnosis and treatment with antiretroviral therapy, making HIV infection a manageable chronic health condition, enabling people living with HIV to lead long and healthy lives, there is no cure for HIV infection. Management of HIV infection is the object of intensive interdisciplinary research. Mathematical modeling approach is widely used for description and analysis of HIV dynamics. HIV infection and disease progression have been carefully studied and well documented, which gives an opportunity to create mathematical models considering the immune defense mechanisms and HIV propagation and adaptation. The scientific problem addressed by the project is to develop a high-resolution multi-scale systems-type mechanistic model of HIV-1 infection dynamics. For this purpose, a systematic review of all known mathematical models of HIV-1 infection was conducted and a strategy of the multi-scale model development has been elaborated. There exist a broad spectrum of mathematical models describing HIV-1 dynamics on the cellular, tissue-specific and organismic levels. However, none of these models can reliably predict the time course of viral load and immune cells density during acute and chronic phases of HIV infection. Development of quantitative systems pharmacology model of HIV infection which integrates clinical and experimental data and knowledge about the disease pathogenesis can lead to improved understanding of how the overall immune system functions during HIV infection and to a rationale search for new therapeutic targets to control viral load. The systems-type model will describe various processes such as target cells (CD4+ T-lymphocytes, macrophages and others) infection, innate and adaptive immune activation, virus elimination and modulation of HIV-host interactions during acute and chronic phase of HIV infection. Systems mechanistic model of HIV infection dynamics will be extended with accounting pharmacokinetics of antiretroviral therapeutics and immunomodulating drugs in order to examine the effect of combination therapy and personalize the HIV infection treatment. To build such systems pharmacology mechanistic model of HIV infection dynamics the modelling tools using ordinary and delayed differential equations will be used. (This study was partly supported by the Russian Science Foundation grant no 18-11-00171 to G.B.)