Adefovir dipivoxil alone or in combination with lamivudine in patients with lamivudine-resistant chronic hepatitis B 1 1The Adefovir Dipivoxil International 461 Study Group includes the following: N. Afdhal (Beth Israel Deaconess Medical Center, Boston, MA); P. Angus (Austin and Repatriation Medical Centre, Melbourne, Australia); Y. Benhamou (Hopital La Pitie Salpetriere, Paris, France); M. Bourliere (Hopital Saint Joseph, Marseille, France); P. Buggisch (Universitaetsklinikum Eppendorf, Department of Medicine, Hamburg, Germany); P. Couzigou (Hopital Haut Leveque, Pessac, France); P. Ducrotte and G. Riachi (Hopital Charles Nicolle, Rouen, France); E. Jenny Heathcote (Toronto Western Hospital, Toronto, Ontario, Canada); H. W. Hann (Jefferson Medical College, Philadelphia, PA); I. Jacobson (New York Presbyterian Hospital, New York, NY); K. Kowdley (University of Washington Hepatology Center, Seattle, WA); P. Marcellin (Hopital Beaujon, Clichy, France); P. Martin (Cedars-Sinai Medical Center, Los Angeles, CA); J. M. Metreau (Centre Hospitalier Universitaire Henri Mondor, Creteil, France); M. G. Peters (University of California, San Francisco, San Francisco, CA); R. Rubin (Piedmont Hospital, Atlanta, GA); S. Sacks (Viridae Clinical Sciences, Inc., Vancouver, Canada); H. Thomas (St. Mary’s Hospital, London, England); C. Trepo (Hopital Hôtel Dieu, Lyon, France); D. Vetter (Hopital Civil, Strasbourg, France); C. L. Brosgart, R. Ebrahimi, J. Fry, C. Gibbs, K. Kleber, J. Rooney, M. Sullivan, P. Vig, C. Westland, M. Wulfsohn, and S. Xiong (Gilead Sciences, Inc., Foster City, CA); D. F. Gray (GlaxoSmithKline, Greenford, Middlesex, England); R. Schilling and V. Ferry (Parexel International, Waltham, MA); and D. Hunt (Covance Laboratories, Princeton, NJ)

Autor: Christian Trepo, Carol L. Brosgart, E. Jenny Heathcote, Mark Sullivan, Paul J. Martin, Robert H. Rubin, D. F. Gray, Ramin Ebrahimi, Marc Bourlière, Kristin Kleber, Peter Buggisch, Shelly Xiong, Marion G. Peters, Kris V. Kowdley, Hie-Won Hann
Rok vydání: 2004
Předmět:
Zdroj: Gastroenterology. 126:91-101
ISSN: 0016-5085
Popis: 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 log 10 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; DAVG 16 was −0.07 in the lamivudine group compared with −2.45 and −2.46 log 10 copies/mL in the adefovir dipivoxil/lamivudine and adefovir dipivoxil monotherapy groups, respectively ( P 10 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.
Databáze: OpenAIRE
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