Treatment of chronic hepatitis C virus infection in Rwanda with ledipasvir-sofosbuvir (SHARED): a single-arm trial
Treatment of chronic hepatitis C virus infection in Rwanda with ledipasvir-sofosbuvir (SHARED): a single-arm trial
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DOI：
10.1016/s2468-1253(18)30382-0
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发表时间：
2019-02-01
影响因子：
35.7
通讯作者：
Grant, Philip M.
中科院分区：
文献类型：
--
作者：
Gupta, Neil;Mbituyumuremyi, Aimable;Grant, Philip M.
背景：撒哈拉以南非洲地区丙型肝炎病毒（HCV）的治疗数据有限，尤其是基因4型。我们的目的是确定ledipasvir-sofosbuvir治疗卢旺达成人慢性HCV基因型1或4感染的安全性和有效性。方法：我们在单一研究地点（卢旺达基加利卢旺达军事医院）进行了一项单组试验，以评估ledipasvir-sofosbuvir治疗慢性HCV感染的卢旺达成人的安全性和有效性。我们招募了年龄在18岁或以上的HCV基因型1或4感染患者，筛查时血浆HCV RNA浓度大于1000 IU/mL。所有参与者服用雷地帕韦（90毫克）和索非布韦（400毫克）的单片联合片剂，每天一次，持续12周。我们使用雅培平台确定HCV基因型，并通过PCR扩增确定HCV亚型。主要终点是治疗后12周持续病毒学应答的参与者比例（SVR12）。所有参与研究的患者都纳入了主要终点分析。本研究已在ClinicalTrials.gov注册，注册号为NCT02964091。在2017年2月6日至9月18日期间招募了300名参与者，随访期于2018年3月1日结束。在基因分型方面，248名（83%）参与者报告为基因4型，4名（1%）为基因1型，48名（16%）为基因1型和基因4型。随后的病毒测序显示，所有参与者实际上都有基因4型感染，其中亚型4k（134[45%]）、亚型4r（48[16%]）、亚型4q（42[14%]）和亚型4v（24[8%]）占主导地位。总体而言，261名（87%,95% CI 83-91）参与者达到SVR12。在基因型4r的参与者中，27名（56%,95% CI 41-71）参与者中观察到SVR12，而234名（93%,90-96）其他亚型的参与者中观察到SVR12。没有因使用ledipasvir-sofosbuvir而导致药物相关治疗中断。最常见的不良事件是高血压（97例[32%]）、头痛（78例[26%]）、头晕（61例[20%]）和疲劳（56例[19%]）。有6例严重不良事件；没有评估是由研究药物引起的。296名参与者在第4周和第8周有药片计数数据；271例（92%）的依从性为100%，只有1例(
Background Limited treatment data are available for hepatitis C virus (HCV) in sub-Saharan Africa, especially for genotype 4. Our objective was to establish the safety and efficacy of ledipasvir-sofosbuvir for chronic HCV genotype 1 or 4 infection in adults in Rwanda.Methods We did a single-arm trial to evaluate the safety and efficacy of ledipasvir-sofosbuvir in Rwandan adults with chronic HCV infection at a single study site (Rwanda Military Hospital, Kigali, Rwanda). We enrolled individuals aged 18 years or older with HCV genotype 1 or 4 infection and a plasma HCV RNA concentration of more than 1000 IU/mL at screening. All participants were given ledipasvir (90 mg) and sofosbuvir (400 mg) in a single combination tablet once daily for 12 weeks. We established HCV genotype using an Abbott platform, and HCV subtype with PCR amplification. The primary endpoint was the proportion of participants with a sustained virological response 12 weeks after therapy (SVR12). All patients enrolled in the study were included in the primary endpoint analyses. This study is registered with ClinicalTrials.gov , number NCT02964091.Findings 300 participants were enrolled between Feb 6, 2017, and Sept 18, 2017, and the follow-up period was completed on March 1, 2018. On genotyping, 248 (83%) participants were reported as having genotype 4, four (1%) genotype 1, and 48 (16%) both genotype 1 and genotype 4. Subsequent viral sequencing showed all participants actually had genotype 4 infection with subtype 4k (134 [45%]), subtype 4r (48 [16%]), subtype 4q (42 [14%]), and subtype 4v (24 [8%]) predominating. Overall, 261 (87%, 95% CI 83-91) participants achieved SVR12. In participants with genotype 4r, SVR12 was observed in 27 (56%, 95% CI 41-71) participants versus 234 (93%, 90-96) individuals with other subtypes. There were no drug-related treatment discontinuations due to ledipasvir-sofosbuvir. The most common adverse events were hypertension (97 [32%]), headache (78 [26%]), dizziness (61 [20%]), and fatigue (56 [19%]). There were six serious adverse events; none were assessed to be due to the study drug. 296 participants had data for pill counts at week 4 and 8; 271 (92%) had 100% adherence and only one (