Efficacy and Safety of Ledipasvir/Sofosbuvir With and Without Ribavirin in Patients With Chronic HCV Genotype 1 Infection Receiving Opioid Substitution Therapy: Analysis of Phase 3 ION Trials
Efficacy and Safety of Ledipasvir/Sofosbuvir With and Without Ribavirin in Patients With Chronic HCV Genotype 1 Infection Receiving Opioid Substitution Therapy: Analysis of Phase 3 ION Trials
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DOI：
10.1093/cid/ciw580
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发表时间：
2016-12-01
影响因子：
11.8
通讯作者：
Dore, Gregory J.
中科院分区：
文献类型：
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作者：
Grebely, Jason;Mauss, Stefan;Dore, Gregory J.
背景基于干扰素的丙型肝炎病毒（HCV）治疗在接受阿片类药物替代治疗（OST）的人群中是安全有效的，但治疗吸收率仍然很低。我们的目的是评估治疗期间OST和药物使用对ledipasvir/sofosbuvir +/-利巴韦林的完成、依从性、持续病毒学应答（SVR 12）和安全性的影响。III期ION研究评估了ledipasvir/sofosbuvir +/-利巴韦林的固定剂量组合在慢性HCV基因型1患者中给药8、12或24周。具有临床意义的药物使用（前12个月）或在筛选时通过尿液药物检测检测到的非大麻素（未通过处方解释）的人不合格。储存的样品可从ION-1通过酶联免疫吸附测定法进行非法药物的回顾性检测。在入组ION研究的1952例患者中，4%（n = 70）接受OST。在接受（n = 70）和未接受OST的患者中（n = 1882），治疗完成情况无差异（97%对98%; P = 0.40），>= 80%的依从性（93%对92%; P = 1.00），SVR 12（94%对97%; P = 0.28）和严重不良事件（4%对3%; P = 0.43）。在ION-1试验的参与者中，23%（n = 196）在治疗期间使用非法药物（15%单独使用大麻素; 8%其他非法药物+/-大麻素）。与使用大麻素和/或其他非法药物的患者相比，治疗期间未使用药物的患者在治疗完成、>= 80%依从性、SVR 12或严重AE方面没有差异。在治疗后24周内未观察到HCV再感染病例。HCV治疗期间的OST和药物使用不影响治疗完成、依从性、SVR 12或安全性。
Background. Interferon-based hepatitis C virus (HCV) therapy is safe and effective among people receiving opioid substitution therapy (OST), but treatment uptake remains low. Our aim was to evaluate the impact of OST and drug use during therapy on completion, adherence, sustained virologic response (SVR12), and safety of ledipasvir/sofosbuvir +/- ribavirin.Methods. The phase 3 ION studies evaluated a fixed-dose combination of ledipasvir/sofosbuvir +/- ribavirin administered for 8, 12, or 24 weeks in patients with chronic HCV genotype 1. People with clinically significant drug use (prior 12 months) or noncannabinoids detected at screening by urine drug tests (not explained by prescriptions) were ineligible. Stored samples were available from ION-1 for retrospective testing for illicit drugs by enzyme-linked immunosorbent assay.Results. Among 1952 patients enrolled in the ION studies, 4% (n = 70) were receiving OST. Among those receiving (n = 70) and not receiving OST (n = 1882), there was no difference in treatment completion (97% vs 98%; P = .40), >= 80% adherence (93% vs 92%; P = 1.00), SVR12 (94% vs 97%; P = .28), and serious adverse events (4% vs 3%; P = .43), respectively. Among participants in the ION-1 trial, 23% (n = 196) used illicit drugs during therapy (15% cannabinoids alone; 8% other illicit drugs +/- cannabinoids). There was no difference in treatment completion, >= 80% adherence, SVR12, or serious AEs in those with no drug use during treatment compared with those who used cannabinoids and/or other illicit drugs. No cases of HCV reinfection were observed in the 24 weeks following treatment.Conclusions. OST and drug use during HCV therapy did not impact treatment completion, adherence, SVR12, or safety.