The Evolutionary Dynamics of HIV Infections

Abstract

Much uncertainty surrounds the detailed mechanisms whereby the human immunodeficiency virus (HIV) causes the acquired immunodeficiency syndrome (AIDS) after a long and variable asymptomatic period. The virus impairs immune responses by infecting and/or killing one of the most important cell populations of the immune system, the CD4 cells. HIV mutates so rapidly that many different variants arise (and coexist) during an individual infection. This article reviews mathematical models that outline the potential importance of this variability as a major factor for the development of AIDS. The essential idea is that the virus evades immune pressure by the continuous production of new mutants resistant to current immunological attack (= antigenic variation). This results in the accumulation of antigenic diversity during the asymptomatic period of the infection. The existence of an antigenic diversity threshold is derived from the interaction between the virus population and the immune cells: CD4 cells mount immune responses, some of which are directed against specific HIV variants, but each virus strain can induce killing of all CD4 cells regardless of their specificity. Therefore increasing HIV diversity enables the virus population to escape from control by the immune system. In this context the observed variability is responsible for the fact that the virus establishes a persistant infection without being cleared by the immune response and induces AIDS after a long and variable incubation period. HIV infections are evolutionary processes on the time scale of a few years. The mathematical models are based on ordinary differential equations. Virus mutation is described by a stochastic process.