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 IFNalpha 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 IFNalpha with a single NRTI or pairs of NRTIs, serially or simultaneously, have been tested. The results of trials of therapy using IFNalpha-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.
Bowden
Scott
S
Victorian Infectious Diseases Reference Laboratory, 10 Wreckyn Street, North Melbourne, Victoria 3051, Australia. scott.bowden@mh.org.au.
Shaw
Tim
T
D000998:Antiviral Agents / Q000627:therapeutic use*; D004334:Drug Administration Schedule; D024882:Drug Resistance, Viral; D004359:Drug Therapy, Combination; D006515:Hepatitis B virus / Q000187:drug effects; D019694:Hepatitis B, Chronic / Q000188:drug therapy*; D006801:Humans; D007155:Immunologic Factors / Q000627:therapeutic use*; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000627:therapeutic use; D011092:Polyethylene Glycols / Q000627:therapeutic use; D011994:Recombinant Proteins; D018894:Reverse Transcriptase Inhibitors / Q000627:therapeutic use*
D000998:Antiviral Agents; D007155:Immunologic Factors; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D011994:Recombinant Proteins; D018894:Reverse Transcriptase Inhibitors; D011092:Polyethylene Glycols; C100416:peginterferon alfa-2a