标题: 恩曲他滨加替诺 v 替诺单药远期疗效和安全性阿德福韦经验 [打印本页] 作者: StephenW 时间: 2013-12-9 14:16 标题: 恩曲他滨加替诺 v 替诺单药远期疗效和安全性阿德福韦经验
Long-term efficacy and safety of emtricitabine plus tenofovir DF vs tenofovir DF monotherapy in adefovir-experienced chronic hepatitis B patients
Thomas Berga, Corresponding author contact information, E-mail the corresponding author,
Fabien Zoulimb,
Bernard Moellerc,
Huy Trinhd,
Patrick Marcelline,
Sing Chanf,
Kathryn M. Kitrinosg,
Phillip Dinhg,
John F. Flaherty Jr.g,
John G. McHutchisong,
Michael Mannsh
a Sektion Hepatologie, Klinik und Poliklinik für Gastroenterologie und RheumatologieUniversitätsklinikum Leipzig, Leipzig, Germany
b INSERM U1052 and Hospices Civils de Lyon, Lyon, France
c Private practice, Berlin, Germany
d Private practice, San Jose, California, USA
e Service d’Hepatologie and INSERM CRB3, University of Paris, Hopital Beaujon, Pavillon Abrami, Paris, France
f Private practice, Flushing, New York, USA
g Gilead Sciences, Inc., Foster City, California, USA
h Department of Gastroenterology, Hepatology and Endocrinology, Medical School of Hannover, Hannover, Germany
Abstract
Background & aims
Suboptimal virologic response to nucleos(t)ide analogs may represent a significant risk factor for resistance development in patients with chronic hepatitis B virus infection; treatment options have not been well studied. We evaluated long-term efficacy and safety of tenofovir alone and in combination with emtricitabine in a prospective, placebo-controlled trial in patients who remained viremic on adefovir therapy.
Methods
Hepatitis B e antigen-positive and -negative patients with hepatitis B virus DNA ⩾1000 copies/mL despite up to 96 weeks of adefovir were randomized to double-blind tenofovir or emtricitabine/tenofovir for 168 weeks. Patients with hepatitis B virus DNA ⩾400 copies/mL (⩾69 IU/mL) at or after week 24 could switch to open-label emtricitabine/tenofovir.
Results
Overall, 90/105 (86%) patients (46/53 tenofovir and 44/52 emtricitabine/tenofovir) completed the 168-week study period, including 74/105 (70%) patients (35/53 tenofovir and 39/52 emtricitabine/tenofovir) who completed the study on their initial randomized treatment. Long-term viral suppression (hepatitis B virus DNA <400 copies/mL) was maintained at week 168 in 84% and 82% of patients receiving either emtricitabine/tenofovir combination or tenofovir monotherapy, respectively (non-completer equal to failure analysis). Baseline viral load as well as the presence of lamivudine and/or adefovir resistance–associated mutations at baseline had no impact on long-term treatment response. No resistance to tenofovir was observed through 168 weeks. Both treatments had a favorable safety profile.
Conclusions
Tenofovir monotherapy is as effective as emtricitabine/tenofovir combination therapy in maintaining long-term viral suppression in patients with a suboptimal response to adefovir, and is well tolerated in this population.
Abbreviations
HBV, hepatitis B virus;
HBeAg, hepatitis B e antigen;
TDF, tenofovir disoproxil fumarate;
FTC, emtricitabine;
ALT, alanine aminotransferase;
ULN, upper limit of normal;
FTC/TDF, emtricitabine/tenofovir disoproxil fumarate;
HBsAg, hepatitis B surface antigen;
pol/RT, polymerase/reverse transcriptase;
NC = F, non-completer equal to failure;
NC/S = F, non-completer or switch equal to failure;
AE, adverse even 作者: StephenW 时间: 2013-12-9 14:16