抗性相关替代率不影响HBV治疗反应

StephenW

November 16, 2018
Rate of Resistance-Related Substitutions Does Not Affect HBV Treatment Response

Results of this study provide a theoretical basis to support the use nucleoside/nucleotide analogues with a high barrier to resistance, such as entecavir or tenofovir, as first-line therapy. Results of this study provide a theoretical basis to support the use nucleoside/nucleotide analogues with a high barrier to resistance, such as entecavir or tenofovir, as first-line therapy.

For patients with hepatitis B virus (HBV), the presence of resistance-associated substitutions does not affect the outcome of therapy if treatments with a high barrier to resistance are used, according to results published in the Journal of Viral Hepatology.

The study included treatment-naive participants with chronic HBV infection (n=232). The researchers used deep sequencing to sequence the nearly full-length HBV reverse transcriptase. They then analyzed the sequences to evaluate the prevalence of resistance-associated substitutions and fitness-associated substitutions at baseline of nucleoside and nucleotide analogues therapy, as well as their effect on treatment responses.


The researchers detected resistance-associated substitutions in 25.0% (n=58) of participants, most commonly at positions involved in lamivudine, telbivudine, and adefovir resistance. Among these participants, 29.3% (n=17) also had fitness-associated substitutions. An additional 53 participants had detectable fitness-associated substitutions not associated with resistance-associated substitutions.

Of the 58 participants with detectable resistance-associated substitutions at baseline, 22 were treated. Follow-up was available for 14 of these participants, all of whom achieved virologic response (undetectable HBV DNA 48-96 weeks after the start of treatment).

"Although [resistance-associated substitutions] were generally present in low proportions in the viral quasispecies, those conferring resistance to lamivudine, adefovir or telbivudine were often found in high proportions, as a result of their good fitness as compared to wild-type viruses," the researchers wrote. "This provides a theoretical basis to support the use [of] nucleoside/nucleotide analogues with a high barrier to resistance, such as entecavir or tenofovir, as first-line therapy, as recommended by international guidelines."


Reference

Chevaliez S, Rodriguez C, Poiteau L, et al. Primary resistance of hepatitis B virus to nucleoside and nucleotide analogues [published online October 19, 2018]. J Viral Hepat. doi: 10.1111/jvh.13025

StephenW

2018年11月16日
抗性相关替代率不影响HBV治疗反应

该研究的结果为支持使用具有高抗性屏障的核苷/核苷酸类似物（例如恩替卡韦或替诺福韦）作为一线治疗提供了理论基础。该研究的结果为支持使用具有高抗性屏障的核苷/核苷酸类似物（例如恩替卡韦或替诺福韦）作为一线治疗提供了理论基础。

根据发表在病毒性肝病学杂志上的结果，对于乙型肝炎病毒（HBV）患者，如果使用具有高抗药性的治疗，那么抗药相关替代的存在不会影响治疗结果。

该研究包括慢性HBV感染的初治患者（n = 232）。研究人员使用深度测序对几乎全长的HBV逆转录酶进行测序。然后，他们分析了这些序列，以评估核苷和核苷酸类似物治疗基线时耐药相关替换和适应性相关替代的流行程度，以及它们对治疗反应的影响。


研究人员在25.0％（n = 58）的参与者中检测到与阻力相关的替代，最常见的是涉及拉米夫定，替比夫定和阿德福韦耐药的位置。在这些参与者中，29.3％（n = 17）也有健身相关替代。另外53名参与者具有可检测的与健康相关的替代，其与抗性相关的替代无关。

在基线时具有可检测的抗性相关取代的58名参与者中，22名被治疗。对这些参与者中的14名进行随访，所有参与者均达到病毒学应答（在治疗开始后48-96周检测不到HBV DNA）。

“尽管[抗性相关取代]通常以较低的比例存在于病毒准种中，但由于与野生型病毒相比具有良好的适应性，因此通常可以高比例地发现对拉米夫定，阿德福韦或替比夫定具有抗性的那些。 “研究人员写道。 “这为支持使用具有高抗性屏障的核苷/核苷酸类似物（例如恩替卡韦或替诺福韦）作为一线治疗提供了理论基础，如国际指南所推荐的那样。”


参考

Chevaliez S，Rodriguez C，Poiteau L，et al。乙型肝炎病毒对核苷和核苷酸类似物的初级耐药性[在线发表于2018年10月19日]。 J病毒肝病。 doi：10.1111 / jvh.13025