A simple model for viral decay dynamics and the distribution of infected cell life spans in SHIV-infected infant rhesus macaques

The dynamics of HIV viral load following the initiation of antiretroviral therapy is not well-described by simple, single-phase exponential decay. Several mathematical models have been proposed to describe its more complex behavior, the most popular of which is two-phase exponential decay. The underlying assumption in two-phase exponential decay is that there are two classes of infected cells with different lifespans. However, with the exception of CD4+ T cells, there is not a consensus on all of the cell types that can become productively infected, and the fit of the two-phase exponential decay to observed data from SHIV.C.CH505 infected infant rhesus macaques was relatively poor. Therefore, we propose a new model for viral decay, inspired by the Gompertz model where the decay rate itself is a dynamic variable. We modify the Gompertz model to include a linear term that modulates the decay rate. We show that this simple model performs as well as the two-phase exponential decay model on HIV and SIV data sets, and outperforms it for the infant rhesus macaque SHIV.C.CH505 infection data set. We also show that by using a stochastic differential equation formulation, the modified Gompertz model can be interpreted as being driven by a population of infected cells with a continuous distribution of cell lifespans, and estimate this distribution for the SHIV.C.CH505-infected infant rhesus macaques. Thus, we find that the dynamics of viral decay in this model of infant HIV infection and treatment may be explained by a distribution of cell lifespans, rather than two distinct cell types.

Automated summary

The dynamics of HIV viral load after antiretroviral therapy initiation is complex and cannot be accurately described by a simple exponential decay model. A new model inspired by the Gompertz model, where the decay rate is a dynamic variable, is proposed. This modified model performs as well as the two-phase exponential decay model for HIV and SIV data, and outperforms it for the infant rhesus macaque SHIV.C.CH505 infection data. It suggests that the dynamics of viral decay in this model may be explained by a distribution of cell lifespans rather than two distinct cell types.