波普瑞韦可用于HIV/HCV共感染的治疗

一项为期44周的多中心Ⅱ期研究显示，在合并感染HIV和丙型肝炎病毒(HCV)的成年患者中，在聚乙二醇干扰素/利巴韦林联合治疗基础上追加波普瑞韦，与加用安慰剂相比可显著提高持续病毒学应答率(SVR)。

Mark S. Sulkowski博士

主要研究者、约翰霍普金斯大学的Mark S. Sulkowski博士说，“在聚乙二醇干扰素/利巴韦林基础上追加1种HCV蛋白酶抑制剂（波普瑞韦或特拉匹韦），已成为单纯HCV基因1型感染的标准治疗。但由于缺乏安全性和疗效数据，在合并感染HIV和HCV的患者中应用HCV蛋白酶抑制剂受到限制。”

这项研究于2010年1月~2010年12月期间在30个研究中心开展，将99例未经治疗的HCV基因1型感染且HIV感染已得到控制的成年患者按照1:2的比例随机分组，给予聚乙二醇干扰素1.5 mcg/kg每周和基于体重的利巴韦林(600~1,400 mg/d)治疗4周，之后在聚乙二醇干扰素/利巴韦林基础上加用安慰剂（对照组）或波普瑞韦800 mg每日3次（波普瑞韦组），治疗44周(Lancet Infect. Dis. 2013;13:597-605)。主要终点为治疗结束后24周随访时的持续病毒学应答（定义为血浆中检测不到HCV RNA）。

结果显示，在99例患者中有98例至少接受了1次治疗用药。其中，64例来自波普瑞韦组，34例来自安慰剂组。研究者报告，在24周随访时，波普瑞韦组和安慰剂组分别有63%和29%的患者达到SVR，差异为33.1%，具有统计学意义(P=0.0008)。与对照组相比，波普瑞韦组发生不良事件的患者比例较高，包括贫血（41% vs. 26%）、发热（36% vs. 21%）、食欲减退（34% vs. 18%）、味觉障碍（28% vs. 15%）、呕吐（28% vs. 15%）以及中性粒细胞减少（19% vs. 6%）。并且，对照组的4例患者和波普瑞韦组的3例患者发生HIV病毒学突破，定义为连续2次HIV RNA数值≥50个拷贝/ml。

“在与聚乙二醇干扰素/利巴韦林联合使用时，波普瑞韦似乎不会显著增加风险，且未报告任何新的不良事件。在同时接受波普瑞韦和HIV蛋白酶抑制剂治疗的患者中，HIV控制的维持情况良好。波普瑞韦与HIV蛋白酶抑制剂之间的药物相互作用对该研究中HCV应答或HIV控制无明显影响。”

研究者总结认为，从HIV/HCV共感染患者24周随访时与SVR相关的肝脏和肝外获益的角度看，波普瑞韦联合聚乙二醇干扰素/利巴韦林治疗可能成为此类合并感染患者的重要治疗选择。

默克公司是商品名为Victrelis的波普瑞韦的销售商。默克公司发起并资助了这项研究。Sulkowski博士及多名合著者披露接受了该公司提供的顾问费和研究资金。

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By: DOUG BRUNK, Ob.Gyn. News Digital Network

Among adults infected with both HIV and hepatitis C virus, the addition of boceprevir to a combination of peginterferon and ribavirin significantly increased the rate of sustained virological response compared with those who received placebo, results from a 44-week, multicenter phase II study demonstrated.

"Rates of SVR at follow-up week 24 were increased with boceprevir in all subgroups of patients, irrespective of demographic or baseline characteristics," researchers led by Dr. Mark S. Sulkowski of Johns Hopkins University, Baltimore, reported in the July issue of the Lancet Infectious Diseases. Although SVR after treatment with peginterferon and ribavirin has been associated with improved survival, "this regimen has been relatively ineffective (SVR, 25%-30%) in patients with HIV and HCV genotype 1 infection," they wrote.
 
"Addition of an HCV protease inhibitor (boceprevir or telaprevir) to peginterferon-ribavirin has emerged as the standard of care for the treatment of HCV genotype 1 infection alone. Use of HCV protease inhibitors in patients infected with HIV and HCV has been restricted by the dearth of available safety and efficacy data."

For the study, which was conducted between Jan. 15 and Dec. 29, 2010, at 30 academic and nonacademic study sites, 99 adults with untreated HCV type 1 genotype infection and controlled HIV were randomized in 1:2 fashion to receive peginterferon 1.5 mcg/kg per week with weight-based ribavirin (600-1,400 mg/day) for 4 weeks, followed by peginterferon-ribavirin plus either placebo (control group) or 800 mg of boceprevir three times daily (boceprevir group) for 44 weeks (Lancet Infect. Dis. 2013;13:597-605).

The primary endpoint of interest was sustained virological response (defined as undetectable plasma HCV RNA) at follow-up week 24 after the end of treatment.

Of the 99 patients, 98 received at least one treatment dose. Of these, 64 were in the boceprevir group and 34 were in the control group. The researchers reported that at follow-up week 24, 63% of patients in the boceprevir group achieved SVR, compared with 29% of controls, a difference of 33.1% that reached significance (P = .0008). Compared with controls, a higher proportion of the boceprevir group experienced adverse events, including anemia (41% vs. 26%, respectively), pyrexia (36% vs. 21%), decreased appetite (34% vs. 18%), dysgeusia (28% vs. 15%), vomiting (28% vs. 15%), and neutropenia (19% vs. 6%). In addition, 4 patients in the control group and 3 in the boceprevir group had HIV viral breakthrough, defined as two consecutive HIV RNA values of at least 50 copies/mL.

"Boceprevir did not seem to add significant risk when used in combination with peginterferon-ribavirin therapy, and no new adverse events were reported," the researchers wrote. "HIV control was well maintained in patients taking boceprevir and HIV protease inhibitors. Drug interactions between boceprevir and HIV protease inhibitors did not have a clinically significant effect on HCV response or HIV control in this study. In view of the hepatic and extrahepatic benefits associated with SVR at follow-up week 24 in patients infected with HIV and HCV, boceprevir in combination with peginterferon-ribavirin might be an important therapeutic option for patients with such coinfection."

Merck markets boceprevir under the brand name Victrelis. Merck sponsored and funded the study. Dr. Sulkowski and numerous other coauthors disclosed having received consulting fees and research grants from the company.