An Evolutionary Model of Progression to AIDS

Abstract

The time to the onset of AIDS symptoms in an HIV infected individual is known to correlate inversely with viremia and the level of immune activation. The correlation exists against the background of strong individual fluctuations demonstrating the existence of hidden variables depending on patient and virus parameters. At the moment, prognosis of the time to AIDS based on patient parameters is not possible. In addition, it is of paramount importance to understand the reason of progression to AIDS in untreated patients to be able to learn to control it by means other than anti-retroviral therapy. Here we develop a mechanistic mathematical model to predict the speed of progression to AIDS in individual untreated patients and patients treated with suboptimal therapy, based on a single-time measurement of several virological and immunological parameters. We show that the gradual increase in virus fitness during a chronic infection causes slow gradual depletion of CD4 T cells. Using the existing evolution models of HIV, we obtain general expressions predicting the time to the onset of AIDS symptoms in terms of the patient parameters, for low-viremia and high-viremia patients separately. We show that the evolution model of AIDS fits the existing data on virus-time correlations better than the alternative model of the deregulation of homeostatic response.