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

StephenW

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

StephenW

远期疗效恩曲他滨加替诺福韦DF和安全性与替诺福韦单药阿德福韦经验的慢性乙肝患者

    托马斯·贝尔加，通讯作者的联系信息，电子邮件通讯作者，
    法比安Zoulimb ，
    伯纳德Moellerc ，
    伊Trinhd ，
    帕特里克Marcelline ，
    唱钱夫，
    凯瑟琳M. Kitrinosg ，
    菲利普Dinhg ，
    约翰·弗莱厄蒂Jr.g ，
    约翰G McHutchisong ，
    迈克尔Mannsh

    一个Sektion Hepatologie ， KLINIK UND Poliklinik献给Gastroenterologie UND RheumatologieUniversitätsklinikum莱比锡，莱比锡，德国
    b INSERM U1052和收容所Civils里昂，里昂，法国
    Ç私人执业，柏林，德国
    ð私人执业，圣何塞，加利福尼亚州，美国
    E服务D' Hepatologie和INSERM CRB3 ，巴黎大学总医院Beaujon ， Pavillon酒店Abrami ，巴黎，法国
    f私人执业，法拉盛，纽约州，美国
    克吉利德科学公司，福斯特城，加利福尼亚州，美国
    胃肠病，肝病和内分泌，汉诺威，德国汉诺威医学院的H系


摘要
背景及目的

次优的病毒学应答对核苷（酸）类似物可能代表了显著危险因素发展的阻力在慢性乙肝病毒感染;治疗方案还没有得到很好的研究。我们评估长期疗效和替诺福韦单独或与恩曲他滨联合在一项前瞻性，安慰剂对照试验中谁留在病毒血症阿德福韦治疗的患者的安全。
方法

乙肝e抗原阳性和阴性患者乙肝病毒DNA ⩾ 1000拷贝/毫升，尽管高达96周阿德福韦被随机双盲替诺福韦或恩曲他滨/替诺福韦168周。患者的乙肝病毒DNA ⩾ 400拷贝/ ml （ ⩾ 69国际单位/毫升）或24周后可以转开放标签恩曲他滨/替诺福韦。
结果

总体而言，90/ 105（ 86 ％ ）的患者（ 53分之46替诺福韦和52分之44恩曲他滨/替诺福韦）完成了168周的研究期间，包括105分之74 （ 70 ％ ）的患者（ 53分之35替诺福韦和52分之39恩曲他滨/替诺福韦）谁完成了研究，他们最初的随机治疗。长期抑制病毒（乙肝病毒DNA < 400拷贝/ ml ）维持在168周的84 ％和82％的患者接受任何恩曲他滨/替诺福韦组合或替诺福韦单药治疗，分别为（非完成者等于故障分析） 。基线病毒载量以及拉米夫定和/或阿德福韦耐药相关突变在基线的存在下，对长期治疗的反应没有影响。替诺福韦无电阻是通过168周观察。两种治疗有良好的安全性。
结论

替诺福韦单药治疗一样有效，恩曲他滨/替诺福韦联合治疗对维持长期抑制病毒在患者对阿德福韦疗效欠佳，且耐受性良好，在这个人口。
缩略语

    乙型肝炎病毒，乙型肝炎病毒;
    大三阳，乙肝e抗原;
    TDF ，富马酸替诺福韦酯;
    美国联邦贸易委员会，恩曲他滨;
    ALT ，丙氨酸氨基转移酶;
    ULN ，正常上限;
    FTC / TDF ，恩曲他滨/富马酸替诺福韦酯;
    乙肝表面抗原，乙肝表面抗原;
    POL / RT ，聚合酶/逆转录酶;
    NC = F ，非完成者等于失败;
    NC / S = F ，非完成者或切换等于失败;
    自动曝光，不良事件