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.
Highlights
Almost all (99.5%) people infected with HIV develop the acquired immunodeficiency syndrome [1,2,3]
Before introducing factors responsible for CD4 T cell depletion, we introduce the two simplest models of virus dynamics predicting an exact balance between the death and replenishment of viremia and target cells
We connect together the models of immunology and evolution to predict the time of progression to AIDS from individual patient’s data
Summary
Almost all (99.5%) people infected with HIV develop the acquired immunodeficiency syndrome [1,2,3]. Suppression of HIV replication with antiretroviral therapy (ART) rapidly increases peripheral blood CD4+ T-cell counts and restores immune function [11,12]. These results show that the immunodeficiency in untreated individuals is caused by the decrease in the CD4+ T cell count and the loss of CD4+ T-cell function, which impairs T cell immunity to pathogens and causes the onset of symptoms within 2–20 years. The effect is reproduced experimentally in nonhuman primates where infection with chimeric simian/human immunodeficiency viruses leads to rapid CD4 T cell depletion, AIDS, and death within 1–2 years [13,14]
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