在接受过治疗的HIV-HCV-1型合并感染患者中，在聚乙二醇干扰素/利巴韦林治疗方案中添加博赛匹韦：来自法国国家艾滋病和病毒性肝炎研究机构（ANRS）HC27研究的疗效、安全性和药代动力学数据
Addition of boceprevir to PEG-interferon/ribavirin in HIV-HCV-Genotype-1-coinfected, treatment-experienced patients: efficacy, safety, and pharmacokinetics data from the ANRS HC27 study.
作者信息
Poizot-Martin Isabelle, Bellissant Eric, Garraffo Rodolphe, Colson Philippe, Piroth Lionel, Solas Caroline, Renault Alain, Bourlière Marc, Halfon Philippe, Ghosn Jade, Alric Laurent, Naqvi Alissa, Carrieri Patrizia, Molina Jean-Michel
机构信息
a Aix-Marseille University, AP-HM Sainte-Marguerite, Service d'Immuno-Hématologie Clinique , Marseille , France.
b INSERM, UMR 912 (SESSTIM) , Marseille , France.
出版信息
HIV Clin Trials. 2016 Mar;17(2):63-71. doi: 10.1080/15284336.2015.1135553. Epub 2016 Feb 11.
BACKGROUND
Scarce data exist on the efficacy and safety of the PEGylated-interferon/ribavirin/boceprevir regimen in HIV/HCV-coinfected patients who failed to respond to PEGylated-interferon/ribavirin treatment.
OBJECTIVES
To evaluate the efficacy and safety of this drug regimen and the impact of the addition of boceprevir(BOC) on atazanavir (ATV) or raltegravir (RAL) pharmacokinetic parameters in a subgroup of patients.
METHODS
In this single-arm phase 2 trial, HIV-1/HCV-genotype-1-coinfected patients received PEGylated-interferonα2b (1.5 μg/kg/week)+ ribavirin (800-1400 mg/day) alone until W4 and with BOC(800 mgTID) until W48. Based on virologic response at W8, the three drugs were stopped or PEGylated-interferon/ribavirin was continued alone until W72. The primary endpoint was SVR at W24 off-therapy (SVR24).
RESULTS
64 patients were included. SVR24 was achieved in 53% of patients (CI90%: 43-63%) and in 90% of previous relapsers. In univariate analysis, SVR24 was associated with response to previous HCV treatment, HCV-1b subtype, HCV-RNA decline, ribavirin-Ctrough at W4, and HCV-RNA at W8 but not to fibrosis score, IL28B genotype, or boceprevir-Ctrough at W8. In multivariate analysis, SVR24 remained associated with response to previous HCV treatment [non-responders versus null responders: OR=5.0(1.3-20.0); relapsers vs. null responders: OR=28.8(4.9-169.5)]. HCV treatment was discontinued for adverse events in 17% of patients. A 51% decrease in ATV/r-AUC0-8 h (p<0.01) and a 57% increase in RAL-AUC0-8 h (p<0.01) were observed, although atazanavir/r or raltegravir did not affect BOC-AUC0-8 h significantly. The ATV mean Cthrough fell from 763.8 ng/mL (CI 95%: 230.3-1297.3) without BOC to 507.7 ng/mL (CI 95%: 164-851.4) with BOC.
CONCLUSIONS
Boceprevir-based regimen demonstrated a high SVR24 rate in treatment-experienced HIV-HCV genotype-1-coinfected relapsers.
背景
关于聚乙二醇化干扰素/利巴韦林/博赛匹韦方案在对聚乙二醇化干扰素/利巴韦林治疗无反应的HIV/HCV合并感染患者中的疗效和安全性的数据稀缺。
目的
评估该药物方案的疗效和安全性，以及在一组患者中添加博赛匹韦（BOC）对阿扎那韦（ATV）或拉替拉韦（RAL）药代动力学参数的影响。
方法
在这项单臂2期试验中，HIV-1/HCV-1基因型合并感染患者单独接受聚乙二醇化干扰素α2b（1.5μg/kg/周）+利巴韦林（800 - 1400mg/天）直至第4周，并联合BOC（800mg每日三次）直至第48周。根据第8周的病毒学反应，停用这三种药物或单独继续使用聚乙二醇化干扰素/利巴韦林直至第72周。主要终点是停药后第24周的持续病毒学应答（SVR24）。
结果
纳入64例患者。53%的患者实现了SVR24（90%置信区间：43 - 63%），既往复发患者中这一比例为90%。在单因素分析中，SVR24与既往HCV治疗反应、HCV-1b亚型、HCV-RNA下降、第4周时利巴韦林的谷浓度以及第8周时的HCV-RNA相关，但与纤维化评分、IL28B基因型或第8周时博赛匹韦的谷浓度无关。在多因素分析中，SVR24仍然与既往HCV治疗反应相关[无反应者与无应答者相比：比值比（OR）=5.0（1.3 - 20.0）；复发者与无应答者相比：OR = 28.8（4.9 - 169.5）]。17%的患者因不良事件停用HCV治疗。观察到ATV/r的药时曲线下面积（AUC0 - 8 h）降低了51%（p<0.01），RAL的AUC0 - 8 h增加了5
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