对 HCV/HIV 合并感染患者 HCV NS5A 耐药相关替换进行超高深度基因组测序。
Ultra-Deep Genomic Sequencing of HCV NS5A Resistance-Associated Substitutions in HCV/HIV Coinfected Patients.
机构信息
University of Cincinnati College of Medicine, 231 Albert Sabin Way, Cincinnati, OH, 45267-0595, USA.
Department of Environmental Health, University of Cincinnati, Cincinnati, OH, 45267, USA.
出版信息
Dig Dis Sci. 2018 Mar;63(3):645-652. doi: 10.1007/s10620-017-4895-1. Epub 2018 Jan 12.
BACKGROUND AND AIMS
The prevalence of naturally occurring HCV-NS5A resistance-associated substitutions (RAS) to DAA drugs might affect the response to treatment in HCV/HIV coinfected subjects. There are limited data on the frequency of HCV-NS5A naturally occurring drug-RAS at baseline in HCV/HIV coinfected patients when ultra-deep sequencing methodologies are applied.
METHODS
HCV-NS5A-RAS were evaluated among 25 subjects in each group. Patients were matched by age, gender, and hepatic fibrosis stage category to control for selection bias.
RESULTS
Within subtype 1a, RAS were observed in 28% of HCV monoinfected and 48% of HCV/HIV coinfected subjects. More patients in the HCV/HIV coinfected group had clinically relevant mutations to DAA directed at NS5A.
CONCLUSION
While the clinical significance of this observation may be limited in highly drug adherent populations, some HCV/HIV coinfected persons may be at greater risk of viral resistance if suboptimal dosing occurs.
背景和目的
自然发生的 HCV-NS5A 耐药相关取代（RAS）对 DAA 药物的流行可能会影响 HCV/HIV 合并感染患者的治疗反应。在应用超深度测序方法时，关于 HCV/HIV 合并感染患者基线时 HCV-NS5A 自然发生的药物-RAS 的频率，数据有限。
方法
在每个组中评估了 25 名患者的 HCV-NS5A-RAS。通过年龄、性别和肝纤维化分期类别对患者进行匹配，以控制选择偏倚。
结果
在 1a 亚型内，HCV 单感染患者中有 28%和 HCV/HIV 合并感染患者中有 48%观察到 RAS。HCV/HIV 合并感染组中更多的患者具有针对 NS5A 的 DAA 治疗的临床相关突变。
结论
虽然在高度药物依从性人群中，这种观察的临床意义可能有限，但如果剂量不足，一些 HCV/HIV 合并感染患者可能面临更大的病毒耐药风险。
Zotero 插件