Why do we not yet have combination chemotherapy for chronic hepatitis B?
Despite the emergence of multidrug-resistant strains of hepatitis B virus (HBV) and previous success with combination therapy for other chronic viral infections, we are still using sequential monotherapy for chronic HBV infection. Antiviral-resistant HBV can result in major life-threatening complications. We now have complementary drugs, such as lamivudine and adefovir dipivoxil, with fundamentally different structures and associated with different signature resistance mutations, with adefovir dipivoxil showing antiviral activity against most lamivudine-resistant strains. Studies of combination therapy to date have used traditional endpoints--short-term reduction of HBV DNA levels and HBeAg seroconversion--rather than evolution of resistance. There is now an emerging body of data suggesting that combination therapy can decrease antiviral resistance in HBV infection, the endpoint likely to be of greatest long-term importance, and, rather than adding or replacing an antiviral agent after resistance develops, it is likely to be more effective in treatment-naive patients.
Sasadeusz
Joseph J
JJ
Victorian Infectious Diseases Service, and Centre for Clinical Research Excellence in Infectious Diseases, Royal Melbourne Hospital, Melbourne, Victoria. Joe.Sasadeusz@mh.org.au
Locarnini
Stephen L
SL
Macdonald
Graeme
G
D000225:Adenine / Q000008:administration & dosage / Q000031:analogs & derivatives; D000914:Antibodies, Viral / Q000097:blood; D000998:Antiviral Agents / Q000008:administration & dosage*; D004279:DNA, Viral / Q000097:blood; D004338:Drug Combinations; D024921:Drug Resistance, Multiple, Viral; D024882:Drug Resistance, Viral; D004357:Drug Synergism; D006513:Hepatitis B e Antigens / Q000097:blood; D006515:Hepatitis B virus / Q000187:drug effects / Q000235:genetics / Q000276:immunology; D019694:Hepatitis B, Chronic / Q000188:drug therapy*; D006801:Humans; D007372:Interferons / Q000627:therapeutic use; D019259:Lamivudine / Q000008:administration & dosage; D063065:Organophosphonates / Q000008:administration & dosage
D000914:Antibodies, Viral; D000998:Antiviral Agents; D004279:DNA, Viral; D004338:Drug Combinations; D006513:Hepatitis B e Antigens; D063065:Organophosphonates; D019259:Lamivudine; D007372:Interferons; D000225:Adenine; C106812:adefovir dipivoxil