Chapter 8 - Sliding mode control theory interprets elite control of HIV

Abstract

It is important to deliver analytical and quantitative methods to evaluate feedback control mechanisms applied by the immune system to control viral infections. Elite control of human immunodeficiency virus (HIV) infection in adults occurs when the immune response suppresses the viral load to undetectable levels without treatment. Since this suppression typically lasts several years, it is important to understand the underlying robustness properties. This chapter investigates why elite control of HIV holds, or fails, in the presence of biological perturbations. The investigations are conducted using a recent model that describes the within-host dynamics of HIV. The novelty of the approach consists in applying the reachability paradigm from sliding mode control theory to assess the robust performance of elite control of HIV. This sliding mode reachability condition defines a fundamental immunological criterion to determine the expected increase or decrease in viral load. Elite control of HIV corresponds to the immune system exhibiting a sliding mode on particular manifolds which prescribe viral clearance. Elite control of HIV also shares the robustness properties of sliding mode control, namely the robustness to uncertainties in the input channel, which is the population dynamic of virus-producing infected cells. Together, these results suggest that sliding mode control theory is a suitable candidate to evaluate T cell immunity in the context of viral infections.