Optimal Disturbances of Bistable Time-Delay Systems Modeling Virus Infections

Functional cure of a chronic virus infection by shifting the virus - host equilibrium state

“…Again, computational approaches can provide useful insight. Amongst them is the recently developed optimal disturbance approach which can predict multi-modal impacts (combination therapies) with maximal effects on the immune system ( 60 ). When applied to LCMV infection, the results demonstrated that a systems shift is possible and requires a combination of different initial state perturbations like virus load and functional T cell state.…”

Bistability analysis of virus infection models with time delays

“…We will use the algorithm proposed in [10] to find all solutions of (5) with a given accuracy ρ in the interval [V 0 , V mvc ], with V 0 given in (7). These solutions will be a complete set of positive steady state values of V .…”

“…For the scenario shown in Figure 5, if the aim is to maximally reduce the equilibrium viral load then the parametric shift should be the one presented in Figure 5D. 7. Conclusions.…”

“…Understanding it is most important for elaboration of an optimal treatment strategy of the offset system dynamics. Indeed, a bistable dynamical system can be transferred to a favourable steady state using the optimal disturbance approach as outlined in [5,6,7]. In the situation of monostability, the transfer of the system away from unwanted steady state requires the implementation of control taking the system to a neighborhood of a given trajectory (e.g., feedback stabilization, extremal shift or the optimal programme (open loop) control [8]).…”

“…The technology includes methods which allow one to compute all steady states for fixed parameter values, to trace them along parameters, and to analyze their stability. Methods for constructing the optimal disturbances were proposed and justified in [5,6,7,25].…”