Current management of HBV antiviral drug resistance

Pietro Lampertico, Mauro Viganò, Massimo Colombo

Research output: Contribution to journalArticlepeer-review


Long-term administration of oral anti-hepatitis B virus (HBV) nucleoside or nucleotide analogues therapy (NUC) is the first-line treatment option for most patients with chronic hepatitis B infection. Although NUC rapidly inhibits HBV replication in most patients, in the long term, this therapeutic regimen is challenged by the emergence of drug-resistant mutant virions, ultimately leading to treatment failure and liver disease progression. Indeed, viral resistance occurs most frequently in patients exposed to first-generation NUC (e.g., lamivudine), whereas second-generation regimens (e.g., adefovir and telbivudine) are definitively safer but still at risk of developing resistance. Third-generation NUCs (e.g., entecavir and tenofovir) are considered safe and unlikely to cause genetic resistance. Drug-resistant strains can be identified by close monitoring of serum levels of HBV DNA before they can attenuate the antiviral response, and can be rescued by a specific "add-on" strategy with a non-cross-resistant drug, to ensure complete long-lasting suppression of HBV. Entecavir and tenofovir are the recommended first-line options in naïve patients to minimize the risk of drug resistance. Tenofovir is the recommended rescue therapy in most patients who fail to respond to nucleoside analogues.

Original languageEnglish
Pages (from-to)120-127
Number of pages8
JournalCurrent Hepatitis Reports
Issue number2
Publication statusPublished - Jun 2011


  • Add-on strategy
  • Antiviral treatment
  • Chronic hepatitis
  • Clinical resistance
  • Drug resistance
  • HBV infection
  • Long-term treatment
  • Nucleoside analogue
  • Nucleotide analogue
  • Rescue therapy

ASJC Scopus subject areas

  • Hepatology
  • Virology


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