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An extension of a previously proposed theory for the pathogenesis of AIDS is presented and analyzed using a mathematical modelling approach. This theory is based on the observation that human immunodeficiency virus type 1 (HIV-1) predominantly infects and replicates in (CD4+)-T cells, and that the infection process within an infected individual is characterized by ongoing generation and selection of HIV variants with increasing reproductive capacity. This evolutionary process is considered to be the reason for the gradual loss of immunocompetence and the final destruction of the immune system observed in most patients. The extension presented here incorporates the effect of the permanently increasing susceptibility of (CD4+)-T cell clones, as a result of the evolutionary process. The presented model reproduces and possibly explains a wide variety of findings about the HIV infection process. Numerical results indicate that the effect of the initial dose is minimal, and restricted to the primary phase of infection. According to the model predictions the impact of the HIV evolutionary speed is crucial for the progression to disease. An important progression determinant is the initial infection rate, being a component of the viral reproductive capacity. An influential role in disease progression seems to be played by the initial (CD4+)-T cell count.

According to a previously proposed mathematical model, the pathogenesis of acquired immunodeficiency syndrome (AIDS) could be explained by two phenomena: direct human immunodeficiency virus (HIV) infection of CD4+ T-cell populations and ongoing generation and selection of HIV mutants with increasing replicative capacity. In the present paper, the results obtained with this model are described in more detail. For different values of biologically interpretable parameters, the model predicts very different patterns of CD4+ T-cell decline after primary infection. With the assumption of a variability of 10% to 25% of three parameters between infected individuals, the model yields a realistic distribution curve of the incubation period to AIDS.

In this paper stochastic simulations of a model for AIDS pathogenesis developed by Nowak and coworkers are presented. The results reveal a strong dependency on initial conditions, and the model predicts a nonmonotonic hazard rate for the transition to AIDS. Doubts are raised concerning the significance of the "antigenic diversity threshold," since it only partially characterizes the model dynamics.