Boceprevir 联合聚乙二醇干扰素 α-2b 和利巴韦林与安慰剂联合聚乙二醇干扰素 α-2b 和利巴韦林治疗 HIV 合并 HCV 基因 1 型感染：一项随机、双盲、对照的 2 期临床试验。
Boceprevir versus placebo with pegylated interferon alfa-2b and ribavirin for treatment of hepatitis C virus genotype 1 in patients with HIV: a randomised, double-blind, controlled phase 2 trial.
机构信息
Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA.
出版信息
Lancet Infect Dis. 2013 Jul;13(7):597-605. doi: 10.1016/S1473-3099(13)70149-X. Epub 2013 Jun 12.
BACKGROUND
Rates of sustained virological response (SVR) to peginterferon-ribavirin are low in patients with hepatitis C virus (HCV) genotype 1 and HIV. We aimed to assess efficacy and safety of triple therapy with boceprevir plus pegylated interferon alfa-2b (peginterferon) and ribavirin, which increases rates of SVR in patients with HCV alone.
METHODS
In our double-blind, randomised controlled phase 2 trial, we enrolled adults (18-65 years) with untreated HCV genotype 1 infection and controlled HIV (HIV RNA <50 copies per mL) at 30 academic and non-academic study sites. We randomly allocated patients (1:2) according to a computer generated sequence, stratified by Metavir score and baseline HCV RNA level, to receive peginterferon 1·5 μg/kg per week with weight-based ribavirin (600-1400 mg per day) for 4 weeks, followed by peginterferon-ribavirin plus either placebo (control group) or 800 mg boceprevir three times per day (boceprevir group) for 44 weeks. Non-nucleoside reverse-transcriptase inhibitors, zidovudine, and didanosine were not permitted. The primary efficacy endpoint was SVR (defined as undetectable plasma HCV RNA) at follow-up week 24 after end of treatment. We assessed efficacy and safety in all patients who received at least one dose of study drug. This study is registered with ClinicalTrials.gov, number NCT00959699.
FINDINGS
From Jan 15, 2010, to Dec 29, 2010, we enrolled 99 patients, 98 of whom received at least one treatment dose. 40 (63%) of 64 patients in the boceprevir group had an SVR at follow-up week 24, compared with ten (29%) of 34 control patients (difference 33·1%, 95% CI 13·7-52·5; p=0·0008). Adverse events were more common in patients who received boceprevir than in control patients: 26 (41%) versus nine (26%) had anaemia, 23 (36%) versus seven (21%) pyrexia, 22 (34%) versus six (18%) decreased appetite, 18 (28%) versus five (15%) dysgeusia, 18 (28%) versus five (15%) vomiting, and 12 (19%) versus two (6%) neutropenia. Three patients who received boceprevir plus peginterferon-ribavirin and four controls had HIV virological breakthrough.
INTERPRETATION
Boceprevir in combination with peginterferon-ribavirin could be an important therapeutic option for patients with HCV and HIV.
FUNDING
Merck.
背景
聚乙二醇干扰素-α-2b（peginterferon）联合利巴韦林治疗丙型肝炎病毒（HCV）基因型 1 合并 HIV 感染患者的持续病毒学应答（SVR）率较低。我们旨在评估 boceprevir 联合聚乙二醇干扰素-α-2b 和利巴韦林三联疗法治疗 HCV 的疗效和安全性，该疗法可提高单纯 HCV 患者的 SVR 率。
方法
在我们的这项双盲、随机对照 2 期临床试验中，我们在 30 家学术和非学术研究机构招募了未经治疗的 HCV 基因型 1 感染且 HIV 得到控制（HIV RNA<50 拷贝/ml）的成年人（18-65 岁）。我们根据计算机生成的序列，按照 Metavir 评分和基线 HCV RNA 水平，将患者（1:2）随机分配，接受每周 1.5 μg/kg 的 peginterferon 联合基于体重的利巴韦林（600-1400mg/天）治疗 4 周，然后接受 peginterferon-ribavirin 联合安慰剂（对照组）或 800mg 博赛泼维每日 3 次（博赛泼维组）治疗 44 周。不允许使用非核苷类逆转录酶抑制剂、齐多夫定和地丹诺辛。主要疗效终点是治疗结束后随访 24 周时的 SVR（定义为不可检测的血浆 HCV RNA）。我们在至少接受一剂研究药物的所有患者中评估了疗效和安全性。这项研究在 ClinicalTrials.gov 注册，编号为 NCT00959699。
结果
从 2010 年 1 月 15 日至 2010 年 12 月 29 日，我们共纳入了 99 例患者，其中 98 例至少接受了一剂治疗药物。博赛泼维组 64 例患者中有 40 例（63%）在随访 24 周时达到 SVR，而对照组 34 例患者中有 10 例（29%）（差异 33.1%，95%CI 13.7-52.5；p=0.0008）。与对照组相比，接受博赛泼维的患者更常出现不良反应：贫血分别为 26 例（41%）和 9 例（26%），发热分别为 23 例（36%）和 7 例（21%），食欲减退分别为 22 例（34%）和 6 例（18%），味觉障碍分别为 18 例（28%）和 5 例（15%），呕吐分别为 18 例（28%）和 5 例（15%），中性粒细胞减少分别为 12 例（19%）和 2 例（6%）。接受博赛泼维联合 peginterferon-ribavirin 和 4 例对照组的 3 例患者出现 HIV 病毒学突破。
结论
博赛泼维联合 peginterferon-ribavirin 可能是 HCV 和 HIV 合并感染患者的重要治疗选择。
资金来源
默克公司。
Zotero 插件