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首页> 外文期刊>Hepatology: Official Journal of the American Association for the Study of Liver Diseases >No resistance to tenofovir disoproxil fumarate detected after up to 144 weeks of therapy in patients monoinfected with chronic hepatitis B virus.
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No resistance to tenofovir disoproxil fumarate detected after up to 144 weeks of therapy in patients monoinfected with chronic hepatitis B virus.

机译：在单次感染慢性乙型肝炎病毒的患者中，经过长达144周的治疗，未检测到对替诺福韦酯富马酸盐的抗药性。

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摘要

Tenofovir disoproxil fumarate (TDF) is a nucleotide analogue with potent activity against human immunodeficiency virus type 1 and hepatitis B virus (HBV). To date, no reports of HBV clinical resistance to TDF have been confirmed. In two phase 3 studies (GS-US-174-0102 and GS-US-174-0103), 375 hepatitis B e antigen-negative (HBeAg(-) ) patients and 266 HBeAg(+) patients with chronic hepatitis B (some nucleoside-naive and some lamivudine-experienced) were randomized 2:1 to receive TDF (n = 426) or adefovir dipivoxil (ADV; n = 215) for 48 weeks. After week 48, eligible patients received open-label TDF with no interruption. The studies are being continued through week 384/year 8; week 144 data are presented here. Per protocol, viremic patients (HBV DNA level >/= 400 copies/mL or 69 IU/mL) had the option of adding emtricitabine (FTC) at or after week 72. Resistance analyses of HBV polymerase/reverse transcriptase (pol/RT) were based on population dideoxy sequencing. Phenotypic analyses were conducted in HepG2 cells with recombinant HBV derived from patient serum. Most patients maintained TDF monotherapy treatment across both studies (607/641, 95%). A resistance analysis of HBV pol/RT was performed at the baseline for all patients, for viremic patients at week 144 or at the last time when they were on TDF monotherapy (34 on TDF and 19 on ADV-TDF), and for patients who remained viremic after the addition of FTC (7/20 on TDF and 5/14 on ADV-TDF). No patient developed amino acid substitutions associated with resistance to TDF. Virological breakthrough on TDF monotherapy was infrequent over 144 weeks (13/426, 3%) and was attributed to documented nonadherence in most cases (11/13, 85%). Persistent viremia (>/=400 copies/mL) through week 144 was rare (5/641, 0.8%) and was not associated with virological resistance to TDF by population or clonal analyses. CONCLUSION: No nucleoside-naive or nucleoside-experienced patient developed HBV pol/RT mutations associated with TDF resistance after up to 144 weeks of exposure to TDF monotherapy.
机译：替诺福韦二富马酸富马酸酯（TDF）是一种核苷酸类似物，对人1型免疫缺陷病毒和乙型肝炎病毒（HBV）具有有效的活性。迄今为止，尚无关于HBV临床对TDF耐药的报道。在两项3期研究（GS-US-174-0102和GS-US-174-0103）中，375例乙型肝炎e抗原阴性（HBeAg（-））患者和266例HBeAg（+）慢性乙型肝炎患者（有些将未使用过核苷的患者和一些接受过拉米夫定治疗的患者按2：1的比例随机接受TDF（n = 426）或阿德福韦酯（ADV; n = 215）治疗48周。在第48周后，符合条件的患者无需中断就接受了开放标签的TDF。研究将持续到第384周/第8年;第144周的数据在这里显示。根据方案，病毒血症患者（HBV DNA水平> / = 400拷贝/ mL或69 IU / mL）可以选择在第72周或之后添加恩曲他滨（FTC）。HBV聚合酶/逆转录酶（pol / RT）的耐药性分析基于群体双脱氧测序。在HepG2细胞中用来自患者血清的重组HBV进行表型分析。在两项研究中，大多数患者维持TDF单一疗法治疗（607/641，95％）。在基线时，对所有患者，在第144周或最后一次接受TDF单药治疗的病毒血症患者（在TDF上为34，在ADV-TDF上为19）进行了HBV pol / RT耐药性分析。加入FTC后仍保持病毒血症（TDF为7/20，ADV-TDF为5/14）。没有患者出现与TDF抗性相关的氨基酸取代。 TDF单药治疗的病毒学突破在144周内很少见（13/426，3％），并且在大多数情况下归因于已记录的不依从性（11/13，85％）。到第144周的持续病毒血症（> / = 400拷贝/ mL）很少（5 / 641，0.8％），并且与人群或克隆分析对TDF的病毒学抗性无关。结论：暴露于TDF单一疗法长达144周后，未曾有过核苷治疗或无核苷经历的患者出现了与TDF耐药性相关的HBV pol / RT突变。

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