Avoiding and managing lamivudine resistance in chronic hepatitis B: current approaches and potential strategies including pegylated interferon.
Since its approval for the treatment of chronic hepatitis B in 1998, lamivudine (LAM) has been used extensively throughout the world, because of its relatively low costs and favourable tolerability. However, clinical trials and cohort studies have demonstrated that a high rate of resistance to this drug develops and, as a result, it is no longer included as a first-line therapy in most current treatment guidelines. Nevertheless, because of its low cost, this drug continues to be used in many countries and the pool of patients who have developed resistance to LAM continues to increase. Thus, there is a clear need to develop coherent management strategies to treat such patients as well as limit the emergence of resistance in the first instance. The purpose of this review is to highlight the need to aim for long-term treatment success while limiting the emergence of drug resistance and its consequences for the future. In addition to add-on/switch strategies with other nucleos(t)ide analogs, currently available data suggest that interferon-based therapies, with their potential to induce a sustained response, are worthy of consideration not only for reducing de novo resistance but as an option for the management of those patients in whom drug resistance has already developed.
Service d'Hépatologie, INSERM-CRB3, Hôpital Beaujon, APHP University of Paris 7, Clichy, France. patrick.marcellin@bjn.aphp.fr
Patrick
P
Marcellin
Joseph
J
Sung
Teerha
T
Piratvisuth
D000225:Adenine / Q000031:analogs & derivatives / Q000627:therapeutic use; D000998:Antiviral Agents / Q000627:therapeutic use*; D024882:Drug Resistance, Viral; D004359:Drug Therapy, Combination; D006147:Guanine / Q000031:analogs & derivatives / Q000627:therapeutic use; D019694:Hepatitis B, Chronic / Q000188:drug therapy*; D006801:Humans; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000627:therapeutic use*; D019259:Lamivudine / Q000627:therapeutic use*; D063065:Organophosphonates / Q000627:therapeutic use; D011092:Polyethylene Glycols / Q000627:therapeutic use*; D011994:Recombinant Proteins; D000068698:Tenofovir
D000998:Antiviral Agents; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D063065:Organophosphonates; D011994:Recombinant Proteins; D019259:Lamivudine; D011092:Polyethylene Glycols; C413685:entecavir; D006147:Guanine; C053001:adefovir; D000068698:Tenofovir; D000225:Adenine; C100416:peginterferon alfa-2a