Tenofovir Disoproxil Fumarate versus Adefovir Dipivoxil for Chronic Hepatitis B

被引：1046

作者：

Marcellin, Patrick ^{[2
,3
]}

Heathcote, E. Jenny ^{[4
]}

Buti, Maria ^{[7
]}

Gane, Ed ^{[8
]}

de Man, Robert A. ^{[10
]}

Krastev, Zahary ^{[11
]}

Germanidis, George ^{[14
]}

Lee, Sam S. ^{[5
]}

Flisiak, Robert ^{[15
]}

Kaita, Kelly ^{[6
]}

Manns, Michael ^{[16
]}

Kotzev, Iskren ^{[12
]}

Tchernev, Konstantin ^{[13
]}

Buggisch, Peter ^{[17
]}

Weilert, Frank ^{[9
]}

Kurdas, Oya Ovung ^{[18
]}

Shiffman, Mitchell L. ^{[19
]}

Trinh, Huy ^{[20
]}

Washington, Mary Kay ^{[21
]}

Sorbel, Jeff ^{[1
]}

Anderson, Jane ^{[1
]}

Snow-Lampart, Andrea ^{[1
]}

Mondou, Elsa ^{[1
]}

Quinn, Joe ^{[1
]}

Rousseau, Franck ^{[1
]}

机构：

[1] Gilead Sci Inc, Durham, NC USA

[2] Univ Paris 07, Hop Beaujon, Assistance Publ Hop Paris, Clichy, France

[3] Hop Beaujon, INSERM, Unite 773, Ctr Rech Claude Bernard Hepatites Virales, Clichy, France

[4] Univ Toronto, Toronto, ON, Canada

[5] Univ Calgary, Calgary, AB, Canada

[6] Univ Manitoba, John Buhler Res Ctr, Winnipeg, MB, Canada

[7] Hosp Gen Valle Hebron, Barcelona, Spain

[8] Middlemore Hosp, Auckland 6, New Zealand

[9] Waikato Hosp, Hamilton, New Zealand

[10] Erasmus Univ, Ctr Med, Rotterdam, Netherlands

[11] Univ Hosp St Ivan Rilsky, Sofia, Bulgaria

[12] Univ Hosp Sveta Marina, Varna, Bulgaria

[13] Med Univ Sofia, Sofia, Bulgaria

[14] Papageorgiou Gen Hosp Thessaloniki, Thessaloniki, Greece

[15] Med Univ Bialystok, Bialystok, Poland

[16] Hannover Med Sch, D-30623 Hannover, Germany

[17] Med Univ Klin Eppendorf, Hamburg, Germany

[18] Haydarpasa Numune Hosp, Istanbul, Turkey

[19] Virginia Commonwealth Univ, Med Ctr, Richmond, VA USA

[20] San Jose Gastroenterol, San Jose, CA USA

[21] Vanderbilt Univ, Med Ctr, Nashville, TN USA

来源：

NEW ENGLAND JOURNAL OF MEDICINE | 2008年 / 359卷 / 23期

关键词：

D O I：

10.1056/NEJMoa0802878

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

Background: Tenofovir disoproxil fumarate (DF) is a nucleotide analogue and a potent inhibitor of human immunodeficiency virus type 1 reverse transcriptase and hepatitis B virus (HBV) polymerase. Methods: In two double-blind, phase 3 studies, we randomly assigned patients with hepatitis B e antigen (HBeAg)-negative or HBeAg-positive chronic HBV infection to receive tenofovir DF or adefovir dipivoxil (ratio, 2:1) once daily for 48 weeks. The primary efficacy end point was a plasma HBV DNA level of less than 400 copies per milliliter (69 IU per milliliter) and histologic improvement (i.e., a reduction in the Knodell necroinflammation score of 2 or more points without worsening fibrosis) at week 48. Secondary end points included viral suppression (i.e., an HBV DNA level of <400 copies per milliliter), histologic improvement, serologic response, normalization of alanine aminotransferase levels, and development of resistance mutations. Results: At week 48, in both studies, a significantly higher proportion of patients receiving tenofovir DF than of those receiving adefovir dipivoxil had reached the primary end point (P<0.001). Viral suppression occurred in more HBeAg-negative patients receiving tenofovir DF than patients receiving adefovir dipivoxil (93% vs. 63%, P<0.001) and in more HBeAg-positive patients receiving tenofovir DF than patients receiving adefovir dipivoxil (76% vs. 13%, P<0.001). Significantly more HBeAg-positive patients treated with tenofovir DF than those treated with adefovir dipivoxil had normalized alanine aminotransferase levels (68% vs. 54%, P=0.03) and loss of hepatitis B surface antigen (3% vs. 0%, P=0.02). At week 48, amino acid substitutions within HBV DNA polymerase associated with phenotypic resistance to tenofovir DF or other drugs to treat HBV infection had not developed in any of the patients. Tenofovir DF produced a similar HBV DNA response in patients who had previously received lamivudine and in those who had not. The safety profile was similar for the two treatments in both studies. Conclusions: Among patients with chronic HBV infection, tenofovir DF at a daily dose of 300 mg had superior antiviral efficacy with a similar safety profile as compared with adefovir dipivoxil at a daily dose of 10 mg through week 48. (ClinicalTrials.gov numbers, NCT00116805 and NCT00117676.).

引用

页码：2442 / 2455

页数：14

共 44 条

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