Andronov-Hopf bifurcation and sensitivity analysis of a time-delay HIV model with logistic growth and antiretroviral treatment

Abstract A mathematical model of the infection of CD4+ T-cells by HIV that includes the effects of treatment by a reverse transcriptase inhibitor (RTI) and a protease inhibitor (PI) is studied. The model includes three populations of CD4+ T-cells (healthy cells, latently-infected cells which cannot produce virus, and productively-infected cells which can produce virus) and two populations of free virus in the blood (infectious virus and non-infectious virus). The model includes a time delay between a T-cell becoming latently infected and productively infected. The model has a virus-free and a chronic infection equilibrium. It is shown that the model has Andronov-Hopf bifurcations leading to limit cycle behavior in the chronic infection region at critical values of the time delays. For three data sets obtained from the work of previous authors, numerical simulations have given critical delay values ranging from approximately 15 days to more than 200 days. This range includes the period of approximately 50 days for intermittent viral blips reported by Rong and Perelson (Plos Comp. Biol. 5(10), 1-18 (2009)). Simple formulas are derived for the sensitivity indices of the equilibrium populations and the basic reproductive number with respect to all parameters in the model. Numerical simulations are carried out to support the analytical results. The numerical results suggest that the most effective methods of reducing both the basic reproductive number and the chronic infection CD4+ T-cell and virus populations are the following: (1) to increase the efficacy of the antiretroviral treatments and (2) to increase virus clearance rate, decrease infection rate, or decrease viral reproduction rate