多种直接作用抗病毒(DAA)方案可用于治疗HCV基因型1感染。然而,目前尚无DAA方案随机对照试验的比较有效性.
我们进行了一项实用的随机对照试验(NCT02786537),以比较DAA对HCV基因型1a或1b对病毒反应的有效性。安全,耐受性,和药物不依从性。成人代偿性肝病,HCV基因型1,未怀孕或母乳喂养,与健康保险可能涵盖ledipasvir/sofosbuvir(LDV/SOF)从34个美国病毒性肝炎诊所招募。参与者被随机(±利巴韦林)接受LDV/SOF,elbasvir/grazoprevir(EBR/GZR),和paritaprevir/ritonavir/ombitasvir+dasabuvir(PrOD;治疗早期停止)。主要结果包括12周时持续的病毒应答(SVR12),临床医生记录的不良事件,患者报告的症状,和药物不依从性。在2016年6月至2018年3月之间,有1,609名参与者被随机分配。在1,128名接受≥1剂EBR/GZR或LDV/SOF(±利巴韦林)的参与者中,SVR12为95.2%(95%CI,92.8%-97.6%)和97.4%(95%CI,95.5%-99.2%),分别,差异估计为2.2%(-0.5%至4.7%),落在“等价”区间内(-5%至5%)。虽然大多数(56%)参与者经历了不良事件,少数为严重(4.2%)或严重(1.8%)。在没有利巴韦林的情况下,由于不良事件导致的停药很少见.患者报告的症状和药物依从性相似。研究的局限性是由于保险拒绝和治疗后随访的损失而退出。限制测量SVR12的能力。
这项实用试验表明,EBR/GZR和LDV/SOF治疗的参与者SVR12高,不良反应少。总的来说,两种方案的疗效相当.结果支持当前的HCV指南,该指南不区分无利巴韦林的EBR/GZR和LDV/SOF。
Multiple direct-acting antiviral (DAA) regimens are available to treat HCV genotype 1 infection. However, comparative effectiveness from randomized controlled trials of DAA regimens is unavailable.
We conducted a pragmatic randomized controlled
trial (NCT02786537) to compare the effectiveness of DAAs for HCV genotype 1a or 1b on viral response, safety, tolerability, and medication nonadherence. Adults with compensated liver disease, HCV genotype 1, not pregnant or breastfeeding, and with health insurance likely to cover ledipasvir/sofosbuvir (LDV/SOF) were recruited from 34 US viral hepatitis clinics. Participants were randomized (± ribavirin) to LDV/SOF, elbasvir/grazoprevir (EBR/GZR), and paritaprevir/ritonavir/ombitasvir+dasabuvir (PrOD; treatment arm stopped early). Primary outcomes included sustained viral response at 12 weeks (SVR12), clinician-recorded adverse events, patient-reported symptoms, and medication nonadherence. Between June 2016 and March 2018, 1,609 participants were randomized. Among 1,128 participants who received ≥1 dose of EBR/GZR or LDV/SOF (± ribavirin), SVR12 was 95.2% (95% CI, 92.8%-97.6%) and 97.4% (95% CI, 95.5%-99.2%), respectively, with a difference estimate of 2.2% (-0.5% to 4.7%), falling within the \"equivalence\" interval (-5% to 5%). While most (56%) participants experienced adverse events, few were serious (4.2%) or severe (1.8%). In the absence of ribavirin, discontinuations due to adverse events were rare. Patient-reported symptoms and medication nonadherence were similar.
Study limitations were dropout due to insurance denial and loss to follow-up after treatment, limiting the ability to measure SVR12.
This pragmatic
trial demonstrated high SVR12 for participants treated with EBR/GZR and LDV/SOF with few adverse effects. Overall, the two regimens were equivalent in effectiveness. The results support current HCV guidelines that do not distinguish between ribavirin-free EBR/GZR and LDV/SOF.