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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Forde, Jonathan E.; Ciupe, Stanca M.; Cintron-Arias, Ariel; and Lenhart, Suzanne. 2016. Optimal Control of Drug Therapy in a Hepatitis B Model. Applied Sciences (Switzerland). Vol.6(8). https://doi.org/10.3390/app6080219