AASLD2014: 替诺福韦单药治疗基因验证耐药性

StephenW

1899
Tenofovir Montherapy in Chronic Hepatitis B Patients with Genotypic Resistance to Previous Antiviral Therapy - a Cohort Study

Jihyun An, Young-Suk Lim, Gi Ae Kim, Hyung-Don Kim, Ju Hyun Shim, Kang Mo Kim, Han Chu Lee, Young-Hwa Chung, Danbi Lee, Yung Sang Lee, Dong Jin Suh;
Department of Gatroenterology and Liver Center, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea

Background/Aims: The antiviral effect of monotherapy with tenofovir disoproxil fumarate (TDF) is controversial for patients with hepatitis B virus (HBV) resistant to nucloes(t)ide analogues.

Methods: Patients who were treated with TDF monotherapy for HBV with documented genotypic resistance mutations were included.

Results: At baseline, 325 (81%) patients had mono-resistance to lamivudine, while others had multi-drug resistance to lamivudine and adefovir (n=43, 10%) or lamivudine and entecavir (n=32, 8%). Most (287, 72%) were being treated with combination therapies including lamivudine, adefovir, and entecavir. Their mean HBV DNA level was 2.5 +/− 2.0 log10 IU/mL. During 1 year of TDF monotherapy, 378 (95%) patients cumulatively achieved virological response (VR, HBV DNA <60 IU/mL) by modified intention-to-treat analysis. The rates of VR were not different between patients with mono-resistance to lamivudine and those with multi-drug resistance (95.2% vs. 92.0%, P =0.27). Sixteen patients who did not achieve VR also showed a significant reduction in their mean HBV DNA levels from baseline (-3.42 log10 IU/mL, P <0.01). Five patients experienced viral breakthrough, and all were related with low adherence to medication. The rate of HBV DNA undetectabil-ity was not influenced by the degree of previous resistance mutations (P >0.05). Four patients discontinued TDF because of gastrointestinal symptoms (n=3) or for pregnancy (n=1). Otherwise, no significant clinical or laboratory adverse event was reported.

Conclusions: In this cohort study, most patients infected with HBV that has genotypic resistance mutations to lamivudine, adefovir, or entecavir rapidly achieved VR within 48 weeks of TDF monotherapy, regardless of the nature of previous resistance mutations. No patient developed additional resistance mutations.

Disclosures:

Young-Suk Lim - Advisory Committees or Review Panels: Bayer Healthcare, Gilead Sciences; Grant/Research Support: Bayer Healthcare, BMS, Gilead Sciences, Novartis

Han Chu Lee - Grant/Research Support: Medigen Biotechnology Co., Novartis, Roche, Bayer HealthCare, Bristol-Myers Squibb, INC research, Boehringer Ingelheim, Taiho Pharmaceutical Co., Yuhan Co.

The following people have nothing to disclose: Jihyun An, Gi Ae Kim, Hyung-Don Kim, Ju Hyun Shim, Kang Mo Kim, Young-Hwa Chung, Danbi Lee, Yung Sang Lee, Dong Jin Suh

StephenW

1899年
替诺福韦单药治疗慢性乙型肝炎患者的基因型抗上​​抗病毒治疗 - 队列研究

Jihyun安，英淑林，GI阂金亨唐金，李惠英沉康默金，韩楚利扬华涌，丹陛李榕生李，董迹嗯徐;
Gatroenterology和肝病中心，峨山医学中心，医学蔚山大学，首尔，韩国系

背景/目的：单药与富马酸替诺福韦酯（TDF）的抗病毒效果是有争议的患者乙型肝炎病毒（HBV）耐药nucloes（）类似物。

方法：谁是病人与TDF单药治疗HBV归档的基因型耐药突变都包括在内。

结果：在基线，325（81％）患者的单耐拉米夫定，而其他人多药耐药拉米夫定和阿德福韦（43例，10％）或拉米夫定和恩替卡韦（32例，8％）。大多数（287，72％）正在接受治疗与联合治疗，包括拉米夫定，阿德福韦和恩替卡韦。他们的平均HBV DNA水平为2.5±2.0日志10国际单位/毫升。 1年内TDF单药治疗，378（95％）的患者累计达到病毒学应答（VR，HBV DNA<60 IU/ mL）的改良意向治疗分析。 VR的速率不是患者的单电阻拉米夫定和那些与多药耐药性（95.2％对92.0％，P =0.27）之间的不同。 16例患者谁没有达到VR也显示，从基线的平均HBV DNA水平显著降低（-3.42日志10 IU/ mL时，P <0.01）。 5例患者发生病毒突破，并全部获得低坚持服药有关。 HBV DNA的速度undetectabil-性不是由以前的耐药突变（P> 0.05）程度的影响。四名病人停止，因为胃肠道症状的TDF（N=3）或妊娠（N=1）。否则，报道没有显著的临床或实验室不良事件。

结论：在此队列研究中，大多数患者感染HBV具有基因型耐药突变拉米夫定，阿德福韦，恩替卡韦或48周TDF单药治疗的内迅速实现虚拟现实，无论前面的耐药突变的性质。没有病人额外的耐药突变。

披露：

英淑林 - 咨询委员会或审查小组：拜耳医药保健，Gilead Sciences公司;格兰特/研究支持：拜耳医药保健，拜耳，Gilead Sciences公司，诺华公司

韩楚李 - 格兰特/研究支持：基亚生物科技有限公司，诺华，罗氏，拜耳医药保健，施贵宝，INC研究，勃林格殷格翰公司，大鹏药业有限公司，遇寒有限公司

下面的人都没有透露：Jihyun的，GI阂金亨唐金，李惠英沉康默金，年轻的华涌，丹陛李榕生李，董机嗯徐