Avoiding the development of drug resistance in the treatment of chronic hepatitis B

With the introduction of the oral antiviral agents lamivudine, adefovir, and entecavir, the treatment course for chronic hepatitis B has been substantially altered. Although these agents offer patients good efficacy coupled with very few side effects, they also have the distinct disadvantage of exerting selective pressure for viral resistance mutations. Drug-resistant patients experience a virologic rebound, followed by altered liver biochemistry and eventual resumption of liver disease. A main goal of treatment is to maximize patient benefit from oral antiviral agents while preventing the development of resistance. This can be aided by understanding the mechanisms of viral resistance and how each agent selects for resistant viral strains. One of the key strategies for the prevention of resistance is selecting an agent or combination of agents for initial therapy that presents a high genetic barrier against viral mutations. Further, once a patient has developed resistance, another important facet of treatment is avoiding the use of sequential monotherapy and instead using effective combinations, as has been demonstrated in the treatment of HIV. In the future, novel combinations of agents that effectively suppress viral mutations may be the rule in the treatment of chronic hepatitis B.