title: Five-year efficacy and safety of tenofovir-based salvage therapy for patients with chronic hepatitis B who previously failed LAM/ADV therapy.
abstract: Multidrug-resistant HBV continues to be an important clinical problem. The TDF-109 study demonstrated that TDF±LAM is an effective salvage therapy through 96 weeks for LAM-resistant patients who previously failed ADV add-on or switch therapy. We evaluated the 5-year efficacy and safety outcomes in patients receiving long-term TDF±LAM in the TDF-109 study.
  
  
  
  A total of 59 patients completed the first phase of the TDF-109 study and 54/59 were rolled over into a long-term prospective open-label study of TDF±LAM 300 mg daily.
  
  
  
  Results are reported at the end of year 5 of treatment. At year 5, 75% (45/59) had achieved viral suppression by intent-to-treat analysis. Per-protocol assessment revealed 83% (45/54) were HBV DNA undetectable. Nine patients remained HBV DNA detectable, however 8/9 had very low HBV DNA levels (<264IU/mL) and did not meet virological criteria for virological breakthrough (VBT). One patient experienced VBT, but this was in the setting of documented non-compliance. The response was independent of baseline LAM therapy or mutations conferring ADV resistance. Four patients discontinued TDF, one patient was lost to follow-up and one died from hepatocellular carcinoma.
  
  
  
  Long-term TDF treatment appears to be safe and effective in patients with prior failure of LAM and a suboptimal response to ADV therapy. These findings confirm that TDF has a high genetic barrier to resistance is active against multidrug-resistant HBV, and should be the preferred oral anti-HBV agent in CHB patients who fail treatment with LAM and ADV.
authors.affiliation: Liver Transplant & Gastroenterology Department, Austin Health, Melbourne, VIC, Australia.|Gastroenterology Department, St Vincent's Hospital, Melbourne, VIC, Australia.|Molecular Research & Development Laboratory, Victorian Infectious Diseases Reference Laboratory, Melbourne, VIC, Australia.|University of Melbourne, Melbourne, VIC, Australia.
authors.forename: Lucy
authors.initials: L
authors.lastname: Lim
authors.affiliation: Gastroenterology Department, St Vincent's Hospital, Melbourne, VIC, Australia.|Molecular Research & Development Laboratory, Victorian Infectious Diseases Reference Laboratory, Melbourne, VIC, Australia.|University of Melbourne, Melbourne, VIC, Australia.
authors.forename: Alexander
authors.initials: A
authors.lastname: Thompson
authors.affiliation: Liver Transplant & Gastroenterology Department, Austin Health, Melbourne, VIC, Australia.
authors.forename: Scott
authors.initials: S
authors.lastname: Patterson
authors.affiliation: Storr Liver Centre, Westmead Millennium Institute for Medical Research, Westmead Hospital & University of Sydney, Sydney, NSW, Australia.
authors.forename: Jacob
authors.initials: J
authors.lastname: George
authors.affiliation: AW Morrow Gastroenterology & Liver Centre, Royal Prince Alfred Hospital, Camperdown, NSW, Australia.
authors.forename: Simone
authors.initials: S
authors.lastname: Strasser
authors.affiliation: Gastroenterology Department, Concord Hospital, Sydney, NSW, Australia.
authors.forename: Alice
authors.initials: A
authors.lastname: Lee
authors.affiliation: Gastroenterology Department, Monash Medical Centre, Melbourne, VIC, Australia.
authors.forename: William
authors.initials: W
authors.lastname: Sievert
authors.affiliation: Gastroenterology & Hepatology Department, Royal Melbourne Hospital, Melbourne, VIC, Australia.|Gastroenterology Department, Eastern Health, Melbourne, VIC, Australia.
authors.forename: Amanda
authors.initials: A
authors.lastname: Nicoll
authors.affiliation: Gastroenterology Department, St Vincent's Hospital, Melbourne, VIC, Australia.|University of Melbourne, Melbourne, VIC, Australia.
authors.forename: Paul
authors.initials: P
authors.lastname: Desmond
authors.affiliation: Gastroenterology Department, Alfred Hospital, Melbourne, VIC, Australia.
authors.forename: Stuart
authors.initials: S
authors.lastname: Roberts
authors.affiliation: Mathematical & Geospatial Sciences Department, RMIT University, Melbourne, VIC, Australia.
authors.forename: Kaye
authors.initials: K
authors.lastname: Marion
authors.affiliation: Molecular Research & Development Laboratory, Victorian Infectious Diseases Reference Laboratory, Melbourne, VIC, Australia.
authors.forename: Scott
authors.initials: S
authors.lastname: Bowden
authors.affiliation: Molecular Research & Development Laboratory, Victorian Infectious Diseases Reference Laboratory, Melbourne, VIC, Australia.|University of Melbourne, Melbourne, VIC, Australia.
authors.forename: Stephen
authors.initials: S
authors.lastname: Locarnini
authors.affiliation: Liver Transplant & Gastroenterology Department, Austin Health, Melbourne, VIC, Australia.|University of Melbourne, Melbourne, VIC, Australia.
authors.forename: Peter
authors.initials: P
authors.lastname: Angus
mesh_terms: D000225:Adenine / Q000627:therapeutic use; D000328:Adult; D000998:Antiviral Agents / Q000627:therapeutic use*; D001315:Australia; D004279:DNA, Viral / Q000097:blood; D024882:Drug Resistance, Viral; D005260:Female; D006515:Hepatitis B virus; D019694:Hepatitis B, Chronic / Q000188:drug therapy*; D006801:Humans; D019259:Lamivudine / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D016016:Proportional Hazards Models; D011446:Prospective Studies; D016879:Salvage Therapy; D000068698:Tenofovir / Q000627:therapeutic use*; D016896:Treatment Outcome; D019562:Viral Load
chemical_list: D000998:Antiviral Agents; D004279:DNA, Viral; D019259:Lamivudine; D000068698:Tenofovir; D000225:Adenine
keywords: antiviral therapy; hepatitis B; hepatology; viral hepatitis