Excitability in the host-pathogen interactions of HIV infection and emergence of viral load blips

Abstract

HIV viral blips are characterized by intermittent episodes of detectable low-level viraemia which return spontaneously to an undetectable level in patients with full suppression of viraemia (<50 copies/ml). The precise mechanisms responsible for viraemia blips and their clinical significance are not known. In this work, we analyze HIV blips using a mathematical model describing basic host-pathogen interactions, in particular regulatory processes involving CD4+, CD8+ T-cells and the virus. We show that under adequate conditions, this interaction system can be excitable and small perturbations of the system by external stimuli can generate robust viral load (VL) blips of regular or irregular frequency and peak amplitudes. Importantly, our analysis showed that direct perturbations of the viral load (by latent reservoirs or opportunistic diseases for example) more efficiently trigger VL blips on contrary to direct perturbations of the immune system, in particular the levels of uninfected CD4+ and cytotoxic CD8+ T-cells. This feature is shown to rely on specific stability properties in this interaction system. Our analysis moreover suggests that blips should be of low clinical significance since any other VL or immune system perturbations could trigger transient viraemia under adequate excitability conditions.