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Combination Therapy for Chronic Hepatitis B Using Capsid Recycling Inhibitor

Rupchand Sutradhar, D C Dalal

TL;DR

If the appropriate drug effectively inhibits reverse transcription, there is no need for an additional inhibitor to block capsid recycling and the impacts of ETV become insignificant.

Abstract

In this paper, we investigate the dynamics of hepatitis B virus infection taking into account the implementation of combination therapy through mathematical modeling. This model is established considering the interplay between uninfected cells, infected cells, capsids, and viruses. Three drugs are considered for specific roles (i) pegylated interferon (PEG IFN) for immune modulation, (ii) lamivudine (LMV) as a reverse-transcriptase inhibitor, and (iii) entecavir (ETV) to block capsid recycling. Using these drugs, three combination therapies are introduced, specifically CT PEG IFN plus LMV, CT PEG IFN plus ETV, and CT PEG IFN plus LMV plus ETV. As a result, when LMV is used in combination therapy with PEG IFN and ETV, the impacts of ETV become insignificant. In conclusion, if the appropriate drug effectively inhibits reverse transcription, there is no need for an additional inhibitor to block capsid recycling.

Combination Therapy for Chronic Hepatitis B Using Capsid Recycling Inhibitor

TL;DR

If the appropriate drug effectively inhibits reverse transcription, there is no need for an additional inhibitor to block capsid recycling and the impacts of ETV become insignificant.

Abstract

In this paper, we investigate the dynamics of hepatitis B virus infection taking into account the implementation of combination therapy through mathematical modeling. This model is established considering the interplay between uninfected cells, infected cells, capsids, and viruses. Three drugs are considered for specific roles (i) pegylated interferon (PEG IFN) for immune modulation, (ii) lamivudine (LMV) as a reverse-transcriptase inhibitor, and (iii) entecavir (ETV) to block capsid recycling. Using these drugs, three combination therapies are introduced, specifically CT PEG IFN plus LMV, CT PEG IFN plus ETV, and CT PEG IFN plus LMV plus ETV. As a result, when LMV is used in combination therapy with PEG IFN and ETV, the impacts of ETV become insignificant. In conclusion, if the appropriate drug effectively inhibits reverse transcription, there is no need for an additional inhibitor to block capsid recycling.
Paper Structure (9 sections, 4 equations, 4 figures)

This paper contains 9 sections, 4 equations, 4 figures.

Table of Contents

  1. Introduction
  2. Model formulation with combination therapy
  3. Steady-states and their stabilities
  4. Numerical simulation
  5. Experiment-1: The effects of CT: PEG-IFN+LMV ($\epsilon_1\neq0,~\epsilon_2\neq 0,~\epsilon_3=0$)
  6. Experiment-2: The effects of CT: PEG-IFN+ETV ($\epsilon_1\neq0,~\epsilon_2=0,~\epsilon_3\neq0$)
  7. Experiment-3: The effects of CT: PEG-IFN+LMV+ETV ($\epsilon_1\neq0,~\epsilon_2\neq0,~\epsilon_3\neq0$)
  8. A comparative examination of the treatments employed in Experiment-1, Experiment-2 and Experiment-3
  9. Conclusions

Figures (4)

  • Figure 1: The effects of therapy are shown here. The solutions of the system \ref{['main model']} are described by (i) Red line: solution without treatment, (ii) Blue line: solution of the system under the CT with PEG-IFN and LMV, (iii) Green line: solution of the system under MT with PEG-IFN, and (iv) Black line: solution of the system under MT with LMV.
  • Figure 2: The effects of therapy are demonstrated here. The solutions of the system \ref{['main model']} are described by (i) Red line: solution without treatment, (ii) Blue line: solution of the system under the CT with PEG-IFN and ETV, (iii) Green line: solution of the system under MT with PEG-IFN, and (iv) Black line: solution of the system under MT with ETV.
  • Figure 3: The effects of combination therapy with three drugs (PEG-IFN+LMV+ETV) are shown here. The solution of the system \ref{['main model']} without treatment is illustrated by the red curves, while the blue curves depict the solution of the system \ref{['main model']} under treatment.
  • Figure 4: The comparison of different therapies. Solid blue line: no treatment, Dash black line: CT: PEG-IFN+LMV, Solid red line: CT: PEG-IFN+ETV, Dash magenta line: CT: PEG-IFN+LMV+ETV.