Optimal multi-drug approaches for reduction of the latent pool in HIV

Abstract

HIV disease is well-controlled by the use of combination antiviral therapy (cART), but lifelong adherence to the prescribed drug regimens is necessary to prevent viral rebound and treatment failure. Populations of quiescently infected cells form a “latent pool” which causes rapid recurrence of viremia whenever antiviral treatment is interrupted. A “cure” for HIV will require a method by which this latent pool may be eradicated. Current efforts are focused on the development of drugs that force the quiescent cells to become active. Previous research has shown that cell-fate decisions leading to latency are heavily influenced by the concentration of the viral protein Tat. While Tat does not cause quiescent cells to become active, in high concentrations it prevents a newly infected cell from becoming quiescent. In this paper, we introduce a model of the effects of two drugs on the latent pool in a patient on background suppressive therapy. The first drug is a quiescent pool stimulator, which acts by causing quiescent cells to become active. The second is a Tat analog, which acts by preventing the creation of new quiescently infected cells. We apply optimal control techniques to explore which combination therapies are optimal for different parameter values of the model.