Towards a new combination therapy with vectored immunoprophylaxis for HIV: Modeling "shock and kill" strategy.

Latently infected cells are considered as a major barrier to curing Human Immunodeficiency Virus (HIV) infection. Reactivation of latently infected cells followed by killing the actively infected cells may be a potential strategy ("shock and kill") to purge the latent reservoir. Based on vectored immunoprophylaxis (VIP) experiment that can elicit bNAbs, in this paper a mathematical model is formulated to explore the efficacy of "shock and kill" strategy with VIP. We derive the basic reproduction number R0 of the model and show that R0 completely determines the dynamics of the model: if R0<1, the disease-free equilibrium is globally asymptotically stable; if R0>1, the system is uniformly persistent. Numerical simulations suggest that the "shock and kill" strategy with VIP can effectively control HIV infection while this strategy cannot eradicate the reservoir without VIP although it can alleviate the HIV infection. To model the administration of drugs and vaccine more realistically, pharmacokinetics and pulse vaccination are incorporated into the model of ordinary differential equations. The resultants are described by impulsive differential equations. The thresholds are obtained for the frequency and strength of the vaccination to eliminate the viruses. Furthermore, the most appropriate times are numerically investigated for starting a short-term latency-reversing agents (LRAs) treatment relative to ART considering the toxicity of LRAs. The results show that LRAs treatment at the beginning of ART might be a better option. These results have important implications for the design of HIV cure-related clinical trials.