Optimal control application to a Kaposi’s sarcoma treatment model

Abstract

Kaposi’s sarcoma (KS) is a malignant disorder of lymphatic endothelial origin that can have two main variants: AIDS-related KS (AKS) and non-AIDS related KS (NAKS) that all share a causal relationship with the human herpesvirus-8 (KSHV or HHV-8). We develop a mathematical model that accounts for B-cells latently and lytically infected with HHV-8 as well as the innate and adaptive arms of the immune system. As a sequel to numerous studies that have investigated the inhibition of HHV-8 endocytosis and reactivation of HHV-8 replication, we employ optimal control strategy to obtain treatment efficacies for these two therapeutic approaches. We have shown that when [Formula: see text] of the B-cell infections result in latency, administration of high efficacy drugs that inhibit entry and reactivation of latently infected B-cells leads to the clearance of KS as the population of infected cells cannot be sustained. Our results also reveal that at [Formula: see text] latency of B-cells, the therapy could produce similar results if the drug that targets viral entry is of moderate efficacy but the efficacy of the drug inhibiting reactivation is considerably more than [Formula: see text] Administration of the same drugs but both at moderate efficacy levels leads to the depletion of both uninfected B- and progenitor cells, a scenario which can lead to the growth of KS variants. When [Formula: see text] of the B-cell infections result in latency, administration with high efficacy drugs reduces the viral entry of HHV-8 but as [Formula: see text] of the infected B-cells are productive, this event leads to production of HHV-8 which ultimately results in more progenitor cells getting infected and the growth of KS. Our findings have the potential to offer more effective therapeutic approaches in the treatment of NAKS.