Hepatitis B: The case for combination therapy

The development of successful treatments for chronic HBV infection has progressed during the past decade as a result of the introduction of PEGylated forms of IFNα and new, orally available nucleoside and nucleotide RT inhibitors (NRTIs). Although treatment with NRTIs causes substantial reductions in HBV DNA levels, the long-term use of NRTIs as monotherapy is compromised by the development of viral resistance. In attempts to minimize the risk of resistance, combination regimens using pegylated IFNα with a single NRTI or pairs of NRTIs, serially or simultaneously, have been tested. The results of trials of therapy using IFNα-NRTI combinations have thus far been disappointing. However, the recent introduction of more efficacious drugs, together with a better understanding of the activities of drug combinations, suggests that, in future, the careful design of combination strategies should lead to improved outcomes, particularly with respect to long-term viral suppression and consequent minimization of drug resistance.