Modeling HIV Dynamics Under Combination Therapy with Inducers and Antibodies.

Abstract

A mathematical model is proposed to simulate the "shock-kill" strategy where broadly neutralizing antibodies (bNAbs) are injected with a combination of HIV latency activators to reduce persistent HIV reservoirs. The basic reproductive ratio of virus is computed to extrapolate how the combinational therapy of inducers and antibodies affects the persistence of HIV infection. Numerical simulations demonstrate that a proper combination of inducers and bNAbs can drive the basic reproductive ratio below unity. Interestingly, it is found that a longer dosage interval leads to the higher HIV survival opportunity and a smaller dosage interval is preferred, which is fundamental to design an optimal therapeutic scheme. Further simulations reveal the conditions under which the joint therapy of inducer and antibodies induces a large extension of viral rebound time, which highlights the mechanism of delayed viral rebound from the experiment (Halper-Stromberg et al. in Cell 158:989-999, 2014). Optimal time for cessation of treatment is also analyzed to aid practical applications.