未经证实:直接抗病毒(DAA)方案可治愈>95%的慢性HCV感染患者。然而,在一些治疗失败的患者中,抗性相关取代(RAS)可以发展,限制再治疗选择,并冒着继续传播抗药性病毒的风险。在这项研究中,我们评估了RAS的患病率和分布,包括新型NS5ARAS和与RAS选择相关的临床因素,在经历DAA治疗失败的患者中。
未经批准:SHARED是一个由临床医生和科学家组成的研究HCV耐药性的国际联盟。收集了来自22个国家的3,355名患者的HCV序列相关元数据。NS3、NS5A、和病毒逻辑故障中的NS5BRAS,包括新颖的NS5A替换,进行了检查。研究了临床和人口统计学特征与RAS选择的关联。
未经评估:在DAA暴露后,RAS的频率从其自然患病率增加:在NS3中为37%至60%,在NS5A中为29%至80%,在NS5B中,索非布韦的15%到22%,dasabuvir的NS5B为24%至37%。在730个病毒学故障中,大多数人都用第一代DAAs治疗,94%的人在≥1个DAA类别中耐药:31%的人在单一类别中耐药,42%的双重抗性(主要针对蛋白酶和NS5A抑制剂),和21%的三重阻力。含有≥2个高抗性RAS的不同模式很常见。在基因型1a中发现了新的潜在NS5ARAS和适应性变化,3和4。DAA故障后,RAS选择在患有肝硬化的老年人和感染基因型1b和4的人群中更为频繁。
未经证实:在DAA治疗失败后,HCV的耐药性很常见。以前未被识别的替代继续出现并且仍然没有特征。
未经证实:尽管直接作用的抗病毒药物可有效治愈大多数患者的丙型肝炎,有时治疗选择耐药病毒,导致抗病毒药物无效或仅部分有效。多药耐药性在DAA治疗失败的患者中很常见。老年患者和晚期肝病患者更容易选择耐药病毒。需要国际社会和各国政府的集体努力,以制定管理耐药性和防止耐药病毒传播的最佳方法。
UNASSIGNED: Direct-acting antiviral (DAA) regimens provide a cure in >95% of patients with chronic HCV infection. However, in some patients in whom therapy fails, resistance-associated substitutions (RASs) can develop, limiting retreatment options and risking onward resistant virus transmission. In this study, we evaluated RAS prevalence and distribution, including novel NS5A RASs and clinical factors associated with RAS selection, among patients who experienced DAA treatment failure.
UNASSIGNED: SHARED is an international consortium of clinicians and scientists studying HCV drug resistance. HCV sequence linked metadata from 3,355 patients were collected from 22 countries. NS3, NS5A, and NS5B RASs in virologic failures, including novel NS5A substitutions, were examined. Associations of clinical and demographic characteristics with RAS selection were investigated.
UNASSIGNED: The frequency of RASs increased from its natural prevalence following DAA exposure: 37% to 60% in NS3, 29% to 80% in NS5A, 15% to 22% in NS5B for sofosbuvir, and 24% to 37% in NS5B for dasabuvir. Among 730 virologic failures, most were treated with first-generation DAAs, 94% had drug resistance in ≥1 DAA class: 31% single-class resistance, 42% dual-class resistance (predominantly against protease and NS5A inhibitors), and 21% triple-class resistance. Distinct patterns containing ≥2 highly resistant RASs were common. New potential NS5A RASs and adaptive changes were identified in genotypes 1a, 3, and 4. Following DAA failure, RAS selection was more frequent in older people with cirrhosis and those infected with genotypes 1b and 4.
UNASSIGNED: Drug resistance in HCV is frequent after DAA treatment failure. Previously unrecognized substitutions continue to emerge and remain uncharacterized.
UNASSIGNED: Although direct-acting antiviral medications effectively cure hepatitis C in most patients, sometimes treatment selects for resistant viruses, causing antiviral drugs to be either ineffective or only partially effective. Multidrug resistance is common in patients for whom DAA treatment fails. Older patients and patients with advanced liver diseases are more likely to select drug-resistant viruses. Collective efforts from international communities and governments are needed to develop an optimal approach to managing drug resistance and preventing the transmission of resistant viruses.