Five-year efficacy and safety of tenofovir-based salvage therapy for patients with chronic hepatitis B who previously failed LAM/ADV therapy

Lucy Lim, Alexander Thompson, Scott Patterson, Jacob George, Simone Strasser, Alice Lee, William Sievert, Amanda Nicoll, Paul Desmond, Stuart Roberts, Kaye Marion, Scott Bowden, Stephen Locarnini, Peter Angus

Research output: Contribution to journalArticleResearchpeer-review

Abstract

Background: 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. Methods: 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: 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. Conclusions: 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.

Original languageEnglish
Pages (from-to)827-835
Number of pages9
JournalLiver International
Volume37
Issue number6
DOIs
Publication statusPublished - Jun 2017
Externally publishedYes

Keywords

  • Antiviral therapy
  • Hepatitis B
  • Hepatology
  • Viral hepatitis

Cite this

Lim, Lucy ; Thompson, Alexander ; Patterson, Scott ; George, Jacob ; Strasser, Simone ; Lee, Alice ; Sievert, William ; Nicoll, Amanda ; Desmond, Paul ; Roberts, Stuart ; Marion, Kaye ; Bowden, Scott ; Locarnini, Stephen ; Angus, Peter. / Five-year efficacy and safety of tenofovir-based salvage therapy for patients with chronic hepatitis B who previously failed LAM/ADV therapy. In: Liver International. 2017 ; Vol. 37, No. 6. pp. 827-835.
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title = "Five-year efficacy and safety of tenofovir-based salvage therapy for patients with chronic hepatitis B who previously failed LAM/ADV therapy",
abstract = "Background: 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. Methods: 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: 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. Conclusions: 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.",
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Five-year efficacy and safety of tenofovir-based salvage therapy for patients with chronic hepatitis B who previously failed LAM/ADV therapy. / Lim, Lucy; Thompson, Alexander; Patterson, Scott; George, Jacob; Strasser, Simone; Lee, Alice; Sievert, William; Nicoll, Amanda; Desmond, Paul; Roberts, Stuart; Marion, Kaye; Bowden, Scott; Locarnini, Stephen; Angus, Peter.

In: Liver International, Vol. 37, No. 6, 06.2017, p. 827-835.

Research output: Contribution to journalArticleResearchpeer-review

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T1 - Five-year efficacy and safety of tenofovir-based salvage therapy for patients with chronic hepatitis B who previously failed LAM/ADV therapy

AU - Lim, Lucy

AU - Thompson, Alexander

AU - Patterson, Scott

AU - George, Jacob

AU - Strasser, Simone

AU - Lee, Alice

AU - Sievert, William

AU - Nicoll, Amanda

AU - Desmond, Paul

AU - Roberts, Stuart

AU - Marion, Kaye

AU - Bowden, Scott

AU - Locarnini, Stephen

AU - Angus, Peter

PY - 2017/6

Y1 - 2017/6

N2 - Background: 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. Methods: 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: 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. Conclusions: 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.

AB - Background: 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. Methods: 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: 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. Conclusions: 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.

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KW - Hepatology

KW - Viral hepatitis

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