Adefovir Dipivoxil Alone or in Combination with Lamivudine in Patients with Lamivudine-Resistant Chronic Hepatitis B

Marion G. Peters, H. W. Hann, Paul Martin, E. Jenny Heathcote, P. Buggisch, R. Rubin, M. Bourliere, K. Kowdley, C. Trepo, D. F. Gray, M. Sullivan, K. Kleber, R. Ebrahimi, S. Xiong, Carol L. Brosgart

Research output: Contribution to journalArticle

543 Citations (Scopus)

Abstract

Background & Aims: Adefovir dipivoxil possesses potent in vitro and in vivo antiviral activity in wild-type hepatitis B. This study assessed the safety and efficacy of adefovir dipivoxil alone and in combination with lamivudine compared with ongoing lamivudine therapy in patients with chronic hepatitis B with compensated liver disease and lamivudine-resistant hepatitis B virus (HBV). Methods: Fifty-nine hepatitis B e antigen (HBeAg)-positive patients with genotypic evidence of lamivudine-resistant HBV, serum alanine aminotransferase (ALT) level ≥1.2 times the upper limit of normal, and serum HBV DNA level ≥6 log10 copies/mL despite ongoing treatment with lamivudine were randomized to adefovir dipivoxil 10 mg, lamivudine 100 mg, or addition of adefovir dipivoxil to ongoing lamivudine daily. The primary end point was the time-weighted average change from baseline in serum HBV DNA level (DAVG) up to week 16. Results: Rapid reductions in serum HBV DNA level were seen by 4 weeks in all recipients of adefovir dipivoxil; DAVG16 was -0.07 in the lamivudine group compared with -2.45 and -2.46 log10 copies/mL in the adefovir dipivoxil/lamivudine and adefovir dipivoxil monotherapy groups, respectively (P < 0.001). Median change from baseline in serum HBV DNA level at week 48 was 0.0, -3.59, and -4.04 log10 copies/mL in the lamivudine, adefovir dipivoxil/lamivudine, and adefovir dipivoxil groups, respectively. ALT level normalized in 10 of 19 (53%) and 9 of 18 (47%) recipients of adefovir dipivoxil/lamivudine and adefovir dipivoxil, respectively, compared with 1 of 19 (5%) recipients of lamivudine. Three patients receiving adefovir dipivoxil or adefovir dipivoxil/lamivudine and none receiving lamivudine monotherapy were HBeAg negative at week 48 and one became hepatitis B surface antigen negative. Conclusions: These data, limited to patients with compensated liver disease, indicate that adefovir dipivoxil alone or in combination with ongoing lamivudine therapy provides effective antiviral therapy in patients with lamivudine-resistant HBV.

Original languageEnglish
Pages (from-to)91-101
Number of pages11
JournalGastroenterology
Volume126
Issue number1 SUPPL. 1
DOIs
StatePublished - Jan 1 2004
Externally publishedYes

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Lamivudine
Chronic Hepatitis B
Hepatitis B virus
Serum
adefovir dipivoxil
Hepatitis B e Antigens
DNA
Alanine Transaminase
Antiviral Agents
Liver Diseases
Therapeutics
Hepatitis B Surface Antigens

ASJC Scopus subject areas

  • Gastroenterology

Cite this

Peters, M. G., Hann, H. W., Martin, P., Heathcote, E. J., Buggisch, P., Rubin, R., ... Brosgart, C. L. (2004). Adefovir Dipivoxil Alone or in Combination with Lamivudine in Patients with Lamivudine-Resistant Chronic Hepatitis B. Gastroenterology, 126(1 SUPPL. 1), 91-101. https://doi.org/10.1053/j.gastro.2003.10.051

Adefovir Dipivoxil Alone or in Combination with Lamivudine in Patients with Lamivudine-Resistant Chronic Hepatitis B. / Peters, Marion G.; Hann, H. W.; Martin, Paul; Heathcote, E. Jenny; Buggisch, P.; Rubin, R.; Bourliere, M.; Kowdley, K.; Trepo, C.; Gray, D. F.; Sullivan, M.; Kleber, K.; Ebrahimi, R.; Xiong, S.; Brosgart, Carol L.

In: Gastroenterology, Vol. 126, No. 1 SUPPL. 1, 01.01.2004, p. 91-101.

Research output: Contribution to journalArticle

Peters, MG, Hann, HW, Martin, P, Heathcote, EJ, Buggisch, P, Rubin, R, Bourliere, M, Kowdley, K, Trepo, C, Gray, DF, Sullivan, M, Kleber, K, Ebrahimi, R, Xiong, S & Brosgart, CL 2004, 'Adefovir Dipivoxil Alone or in Combination with Lamivudine in Patients with Lamivudine-Resistant Chronic Hepatitis B', Gastroenterology, vol. 126, no. 1 SUPPL. 1, pp. 91-101. https://doi.org/10.1053/j.gastro.2003.10.051
Peters, Marion G. ; Hann, H. W. ; Martin, Paul ; Heathcote, E. Jenny ; Buggisch, P. ; Rubin, R. ; Bourliere, M. ; Kowdley, K. ; Trepo, C. ; Gray, D. F. ; Sullivan, M. ; Kleber, K. ; Ebrahimi, R. ; Xiong, S. ; Brosgart, Carol L. / Adefovir Dipivoxil Alone or in Combination with Lamivudine in Patients with Lamivudine-Resistant Chronic Hepatitis B. In: Gastroenterology. 2004 ; Vol. 126, No. 1 SUPPL. 1. pp. 91-101.
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abstract = "Background & Aims: Adefovir dipivoxil possesses potent in vitro and in vivo antiviral activity in wild-type hepatitis B. This study assessed the safety and efficacy of adefovir dipivoxil alone and in combination with lamivudine compared with ongoing lamivudine therapy in patients with chronic hepatitis B with compensated liver disease and lamivudine-resistant hepatitis B virus (HBV). Methods: Fifty-nine hepatitis B e antigen (HBeAg)-positive patients with genotypic evidence of lamivudine-resistant HBV, serum alanine aminotransferase (ALT) level ≥1.2 times the upper limit of normal, and serum HBV DNA level ≥6 log10 copies/mL despite ongoing treatment with lamivudine were randomized to adefovir dipivoxil 10 mg, lamivudine 100 mg, or addition of adefovir dipivoxil to ongoing lamivudine daily. The primary end point was the time-weighted average change from baseline in serum HBV DNA level (DAVG) up to week 16. Results: Rapid reductions in serum HBV DNA level were seen by 4 weeks in all recipients of adefovir dipivoxil; DAVG16 was -0.07 in the lamivudine group compared with -2.45 and -2.46 log10 copies/mL in the adefovir dipivoxil/lamivudine and adefovir dipivoxil monotherapy groups, respectively (P < 0.001). Median change from baseline in serum HBV DNA level at week 48 was 0.0, -3.59, and -4.04 log10 copies/mL in the lamivudine, adefovir dipivoxil/lamivudine, and adefovir dipivoxil groups, respectively. ALT level normalized in 10 of 19 (53{\%}) and 9 of 18 (47{\%}) recipients of adefovir dipivoxil/lamivudine and adefovir dipivoxil, respectively, compared with 1 of 19 (5{\%}) recipients of lamivudine. Three patients receiving adefovir dipivoxil or adefovir dipivoxil/lamivudine and none receiving lamivudine monotherapy were HBeAg negative at week 48 and one became hepatitis B surface antigen negative. Conclusions: These data, limited to patients with compensated liver disease, indicate that adefovir dipivoxil alone or in combination with ongoing lamivudine therapy provides effective antiviral therapy in patients with lamivudine-resistant HBV.",
author = "Peters, {Marion G.} and Hann, {H. W.} and Paul Martin and Heathcote, {E. Jenny} and P. Buggisch and R. Rubin and M. Bourliere and K. Kowdley and C. Trepo and Gray, {D. F.} and M. Sullivan and K. Kleber and R. Ebrahimi and S. Xiong and Brosgart, {Carol L.}",
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T1 - Adefovir Dipivoxil Alone or in Combination with Lamivudine in Patients with Lamivudine-Resistant Chronic Hepatitis B

AU - Peters, Marion G.

AU - Hann, H. W.

AU - Martin, Paul

AU - Heathcote, E. Jenny

AU - Buggisch, P.

AU - Rubin, R.

AU - Bourliere, M.

AU - Kowdley, K.

AU - Trepo, C.

AU - Gray, D. F.

AU - Sullivan, M.

AU - Kleber, K.

AU - Ebrahimi, R.

AU - Xiong, S.

AU - Brosgart, Carol L.

PY - 2004/1/1

Y1 - 2004/1/1

N2 - Background & Aims: Adefovir dipivoxil possesses potent in vitro and in vivo antiviral activity in wild-type hepatitis B. This study assessed the safety and efficacy of adefovir dipivoxil alone and in combination with lamivudine compared with ongoing lamivudine therapy in patients with chronic hepatitis B with compensated liver disease and lamivudine-resistant hepatitis B virus (HBV). Methods: Fifty-nine hepatitis B e antigen (HBeAg)-positive patients with genotypic evidence of lamivudine-resistant HBV, serum alanine aminotransferase (ALT) level ≥1.2 times the upper limit of normal, and serum HBV DNA level ≥6 log10 copies/mL despite ongoing treatment with lamivudine were randomized to adefovir dipivoxil 10 mg, lamivudine 100 mg, or addition of adefovir dipivoxil to ongoing lamivudine daily. The primary end point was the time-weighted average change from baseline in serum HBV DNA level (DAVG) up to week 16. Results: Rapid reductions in serum HBV DNA level were seen by 4 weeks in all recipients of adefovir dipivoxil; DAVG16 was -0.07 in the lamivudine group compared with -2.45 and -2.46 log10 copies/mL in the adefovir dipivoxil/lamivudine and adefovir dipivoxil monotherapy groups, respectively (P < 0.001). Median change from baseline in serum HBV DNA level at week 48 was 0.0, -3.59, and -4.04 log10 copies/mL in the lamivudine, adefovir dipivoxil/lamivudine, and adefovir dipivoxil groups, respectively. ALT level normalized in 10 of 19 (53%) and 9 of 18 (47%) recipients of adefovir dipivoxil/lamivudine and adefovir dipivoxil, respectively, compared with 1 of 19 (5%) recipients of lamivudine. Three patients receiving adefovir dipivoxil or adefovir dipivoxil/lamivudine and none receiving lamivudine monotherapy were HBeAg negative at week 48 and one became hepatitis B surface antigen negative. Conclusions: These data, limited to patients with compensated liver disease, indicate that adefovir dipivoxil alone or in combination with ongoing lamivudine therapy provides effective antiviral therapy in patients with lamivudine-resistant HBV.

AB - Background & Aims: Adefovir dipivoxil possesses potent in vitro and in vivo antiviral activity in wild-type hepatitis B. This study assessed the safety and efficacy of adefovir dipivoxil alone and in combination with lamivudine compared with ongoing lamivudine therapy in patients with chronic hepatitis B with compensated liver disease and lamivudine-resistant hepatitis B virus (HBV). Methods: Fifty-nine hepatitis B e antigen (HBeAg)-positive patients with genotypic evidence of lamivudine-resistant HBV, serum alanine aminotransferase (ALT) level ≥1.2 times the upper limit of normal, and serum HBV DNA level ≥6 log10 copies/mL despite ongoing treatment with lamivudine were randomized to adefovir dipivoxil 10 mg, lamivudine 100 mg, or addition of adefovir dipivoxil to ongoing lamivudine daily. The primary end point was the time-weighted average change from baseline in serum HBV DNA level (DAVG) up to week 16. Results: Rapid reductions in serum HBV DNA level were seen by 4 weeks in all recipients of adefovir dipivoxil; DAVG16 was -0.07 in the lamivudine group compared with -2.45 and -2.46 log10 copies/mL in the adefovir dipivoxil/lamivudine and adefovir dipivoxil monotherapy groups, respectively (P < 0.001). Median change from baseline in serum HBV DNA level at week 48 was 0.0, -3.59, and -4.04 log10 copies/mL in the lamivudine, adefovir dipivoxil/lamivudine, and adefovir dipivoxil groups, respectively. ALT level normalized in 10 of 19 (53%) and 9 of 18 (47%) recipients of adefovir dipivoxil/lamivudine and adefovir dipivoxil, respectively, compared with 1 of 19 (5%) recipients of lamivudine. Three patients receiving adefovir dipivoxil or adefovir dipivoxil/lamivudine and none receiving lamivudine monotherapy were HBeAg negative at week 48 and one became hepatitis B surface antigen negative. Conclusions: These data, limited to patients with compensated liver disease, indicate that adefovir dipivoxil alone or in combination with ongoing lamivudine therapy provides effective antiviral therapy in patients with lamivudine-resistant HBV.

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