Evolutionary game theoretic strategy for optimal drug delivery to influence selection pressure in treatment of HIV-1.

Cytotoxic T-lymphocyte (CTL) escape mutation is associated with long-term behaviors of human immunodeficiency virus type 1 (HIV-1). Recent studies indicate heterogeneous behaviors of reversible and conservative mutants while the selection pressure changes. The purpose of this study is to optimize the selection pressure to minimize the long-term virus load. The results can be used to assist in delivery of highly loaded cognate peptide-pulsed dendritic cells (DC) into lymph nodes that could change the selection pressure. This mechanism may be employed for controlled drug delivery. A mathematical model is proposed in this paper to describe the evolutionary dynamics involving viruses and T cells. We formulate the optimization problem into the framework of evolutionary game theory, and solve for the optimal control of the selection pressure as a neighborhood invader strategy. The strategy dynamics can be obtained to evolve the immune system to the best controlled state. The study may shed light on optimal design of HIV-1 therapy based on optimization of adaptive CTL immune response.