Dynamics of a new HIV model with the activation status of infected cells

Abstract

The activation status can dictate the fate of an HIV-infected CD4+ T cell. Infected cells with a low level of activation remain latent and do not produce virus, while cells with a higher level of activation are more productive and thus likely to transfer more virions to uninfected cells during cell-to-cell transmission. How the activation status of infected cells affects HIV dynamics under antiretroviral therapy remains unclear. We develop a new mathematical model that structures the population of infected cells continuously according to their activation status. The effectiveness of antiretroviral drugs in blocking cell-to-cell viral transmission decreases as the level of activation of infected cells increases because the more virions are transferred from infected to uninfected cells during cell-to-cell transmission, the less effectively the treatment is able to inhibit the transmission. The basic reproduction number \\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$$R_{0}$$\\end{document}R0 of the model is shown to determine the existence and stability of the equilibria. Using the principal spectral theory and comparison principle, we show that the infection-free equilibrium is locally and globally asymptotically stable when \\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$$R_{0}$$\\end{document}R0 is less than one. By constructing Lyapunov functional, we prove that the infected equilibrium is globally asymptotically stable when \\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$$R_{0}$$\\end{document}R0 is greater than one. Numerical investigation shows that even when treatment can completely block cell-free virus infection, virus can still persist due to cell-to-cell transmission. The random switch between infected cells with different activation levels can also contribute to the replenishment of the latent reservoir, which is considered as a major barrier to viral eradication. This study provides a new modeling framework to study the observations, such as the low viral load persistence, extremely slow decay of latently infected cells and transient viral load measurements above the detection limit, in HIV-infected patients during suppressive antiretroviral therapy.