  Sequential monotherapy is the most widely used therapeutic approach in the
treatment of HBV chronic infection. Unfortunately, under therapy, in some
patients the hepatitis virus mutates and gives rise to variants which are drug
resistant. We conjecture that combination therapy is able to delay drug
resistance for a longer time than sequential monotherapy. To study the action
of these two therapeutic approaches in the event of unknown mutations and to
explain the emergence of drug resistance, we propose a stochastic model for the
infection within a patient which is treated with two drugs, either sequentially
or contemporaneously, and develops a two-step mutation which is resistant to
both drugs. We study the deterministic approximation of our stochastic model
and give a biological interpretation of its asymptotic behaviour. We compare
the time when this new strain first reaches detectability in the serum viral
load. Our results show that the best choice is to start an early combination
therapy, which allows to stay drug-resistance free for a longer time.
