One of the concerns many people have when taking oral antiviral drugs is drug resistance. So, what is drug resistance all about? Why does drug resistance occur? Drug resistance is due to a genetic mutation in the DNA sequence of the virus, which significantly reduces the efficacy of the oral medication previously taken, leading to a rebound of the virus and a recurrence and aggravation of the disease. Is lamivudine the most resistant drug among the several nucleoside drugs currently available? How long is it usually taken before resistance may occur? Lamivudine has a high resistance rate, with cases of resistance generally occurring after one year. What is the probability of resistance occurring with several other drugs? How long will it take for resistance to occur? Entecavir has a relatively low resistance rate and resistance occurs late.