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Combination antiviral drug therapy improves the survival rates of patients chronically infected with hepatitis B virus by controlling viral replication and enhancing immune responses. Some of these drugs have side effects that make them unsuitable for long-term administration. To address the trade-off between the positive and negative effects of the combination therapy, we investigated an optimal control problem for a delay differential equation model of immune responses to hepatitis virus B infection. Our optimal control problem investigates the interplay between virological and immunomodulatory effects of therapy, the control of viremia and the administration of the minimal dosage over a short period of time. Our numerical results show that the high drug levels that induce immune modulation rather than suppression of virological factors are essential for the clearance of hepatitis B virus.

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c 2016 by the authors; licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC-BY) license (

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Creative Commons Attribution 4.0 International License
This work is licensed under a Creative Commons Attribution 4.0 International License.