HIV evolution and progression of the infection to AIDS

Abstract: In this paper, we propose and discuss a possible mechanism, which, via continuous mutations and evolution, eventually enables HIV to break from immune control. In order to investigate this mechanism, we employ a simple mathematical model, which describes the relationship between evolving HIV and the specific CTL response and explicitly takes into consideration the role of CD4+T cells (helper T cells) in the activation of the CTL response. Based on the assumption that HIV evolves towards higher replication rates, we quantitatively analyze the dynamical properties of this model. The model exhibits the existence of two thresholds, defined as the immune activation threshold and the immunodeficiency threshold, which are critical for the activation and persistence of the specific cell-mediated immune response: the specific CTL response can be established and is able to effectively control an infection when the virus replication rate is between these two thresholds. If the replication rate is below the immune activation threshold, then the specific immune response cannot be reliably established due to the shortage of antigen-presenting cells. Besides, the specific immune response cannot be established when the virus replication rate is above the immunodeficiency threshold due to low levels of CD4+T cells. The latter case implies the collapse of the immune system and beginning of AIDS. The interval between these two thresholds roughly corresponds to the asymptomatic stage of HIV infection. The model shows that the duration of the asymptomatic stage and progression of the disease are very sensitive to variations in the model parameters. In particularly, the rate of production of the naive lymphocytes appears to be crucial. [Copyright &y& Elsevier]