HIV-1 evolution and disease progression.

REFERENCES AND NOTES se that destroys the host. Thus, within a particular host, diversity is driven by the collective sum of all the selective forces acting on the HIV-1 quasispecies virus population, rather than a specific immune parameter by or in itself (4). The theory predicts two possible outcomes. First, infected individuals with diversity higher than their individual specific threshold lose immune control and rapidly progress to AIDS, while those below their individual specific threshold remain clinically stable. Second, an increase in antigenic diversity over time in the same individual gives rise to loss of immune control and faster progression to AIDS once the individual's specific threshold is crossed. The fact that the magnitude of the diversity threshold could be different in different infected individuals is a result of the inherent plasticity of the mathematical model used to derive the antigenic diversity threshold theory (1, 2). As a consequence, the model becomes virtually untestable. The actual model could encompass many different possible parameters that can trigger the trajectory to AIDS, all of which are sensitive to initial conditions (5) and better expressed as a nondimensional threshold condition (6). Thus, stochastic simulations of the infection process only partially characterize the model dynamics (5). The results of our study (7) do not support a model that relates increasing antigenic diversity to pathogenic progres-