Computer Simulations of Slow Progression of Human Immunodeficiency Virus Infection and Relapse during Anti-HIV Treatment with Reverse Transcriptase Inhibitors and Protease Inhibitors

Human immunodeficiency virus (HIV) infection and acquired immunodeficiency syndrome (AIDS) have been very serious problems since the 1980s. The progression of HIV infection into AIDS can be suppressed to some extent with reverse transcriptase inhibitors (RTIs) and protease inhibitors (PIs); however, there are some serious problems with treatments using the anti-HIV drugs (e.g. very high expense, complicated administration, and drug resistance). Hence, more studies on HIV and the development of more effective anti-HIV treatments are required. We consider it important to understand the complex dynamics involved in HIV infection, and we therefore propose new mathematical models of HIV infection. In the modeling, we have paid attention to the nonlinear relations between stimuli and responses (i.e., when responses are plotted against the logarithm of stimuli, a sigmoid curve is obtained), and to lymphoid organs which seem more important than the blood compartment (i.e., lymphoid organs are major reservoirs of HIV virions and contain most of the lymphocytes). Using the models, we have found that viral antigenic mutation plays an important role in the slow progression in the chronic phase of HIV infection. We have also found that viral antigenic mutation can cause relapse of HIV infection when the inhibition rate of anti-HIV drugs is low and that viral antigenic mutation cannot cause relapse when the inhibition rate is high.