Modelling Multiple Dosing with Drug Holiday in Antiretroviral Treatment on HIV-1 Infection

Abstract

Abstract.A within-host mathematical model to describe the dynamics of target cells and viral load in early HIV-1 infection was developed, which incorporates a combination of RTI and PI treatments by using a pharmacokinetics model. The local stability of uninfected steady state for the model was determined using an alternative threshold. The pharmacokinetics model was employed to estimate drug efficacy in multiple drug dosing. The effect of periodic drug efficacy of pharmacokinetic type on outcome of HIV-1 infection was explored under various treatment interruptions. The effectiveness of treatment interruption was determined according to the time period of the drug holidays. The results showed that long drug holidays lead to therapy failure. Under interruption of treatments combining RTI and PI therapy, effectiveness of the treatment requires a short duration of the drug holiday.

Optimal Control Approach For HIV-1 Infection in CD4+T Cells with RTI and PI Treatments

“…In this section, the proposed mathematical model is explained in detail. The mathematical model is developed from [1], [6], [7]. In [1], Sivastava et al did not incorporating cellcell viral transmission.…”

“…The drug response of target cells depends on the characteristic of immune cells, thereby the immune system of each individual shows different drug response. In the model, they divided Langerhans and CD4+ T cells into sub classes namely: sub class containing the active drugs and subclass which is not acquiring drugs [6], [7]. Sutimin et al developed and analyzed a mathematical model incorporating the infection process through cell to cell contact of CD4+T cells, CTL compartment and the combination of RTI and PI treatments [8].…”

Modeling CD4+ T cells and CTL response in HIV-1 infection with antiretroviral therapy

“…reproduction ratio to analyze the dynamics of the model. A model by considering the effect of RTI and PI drugs was proposed by Sutimin et.al to study the immune response of drugs in HIV-1 infection [12], [13].…”

“…As in [11], [12], [13], sub-ratio Ti →Ti indicates the infection path from an infected CD4 + T cell to healthy CD4 + T cells. Sub-ratio Ti →V →Ti indicates the infection path from infected CD4 + T cell then reproduces new viral particles infecting healthy CD4 + T cells.…”

“…A model was proposed by Chirove et al [11] and Sutimin et al [12], [13], to capture HIV-1 the infection of Langerhans and CD4 + T cells in early HIV-1 infection. Chirove et al used…”