在接受过治疗的hiv - hcv -基因型-1共感染患者中，在peg -干扰素/利巴韦林的基础上添加博昔普韦:来自ANRS HC27研究的疗效、安全性和药代动力学数据

Q2 Medicine HIV Clinical Trials Pub Date : 2016-03-01 Epub Date: 2016-02-11 DOI:10.1080/15284336.2015.1135553

Isabelle Poizot-Martin, Eric Bellissant, Rodolphe Garraffo, Philippe Colson, Lionel Piroth, Caroline Solas, Alain Renault, Marc Bourlière, Philippe Halfon, Jade Ghosn, Laurent Alric, Alissa Naqvi, Patrizia Carrieri, Jean-Michel Molina

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引用次数: 5

摘要

背景:关于聚乙二醇化干扰素/利巴韦林/博昔普韦方案对聚乙二醇化干扰素/利巴韦林治疗无效的HIV/ hcv合并感染患者的有效性和安全性的数据很少。目的:评估该药物方案的有效性和安全性，以及在亚组患者中添加博昔普韦(BOC)对阿扎那韦(ATV)或雷替格拉韦(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 -基因型-1共感染患者单独接受聚乙二醇干扰素α2b (1.5 μg/kg/周)+利巴韦林(800-1400 mg/天)治疗至W4，并与BOC(800 mgTID)联合治疗至W48。根据W8时的病毒学反应，停用三种药物或继续单独使用聚乙二醇干扰素/利巴韦林至W72。主要终点是停药后24小时的SVR (SVR24)。结果:共纳入64例患者。53%的患者(CI90%: 43-63%)和90%的既往复发患者达到了SVR24。在单因素分析中，SVR24与先前HCV治疗的反应、HCV-1b亚型、HCV- rna下降、W4时的利巴韦林-穿透率和W8时的HCV- rna有关，但与纤维化评分、IL28B基因型或W8时的boceprevir-穿透率无关。在多变量分析中，SVR24仍然与先前HCV治疗的反应相关[无反应者与无反应者:OR=5.0(1.3-20.0);复发者与无应答者:OR=28.8(4.9-169.5)]。17%的患者因不良事件而停止丙肝治疗。ATV/r-AUC0-8 h降低51%(结论:boceprevir为基础的方案在治疗经历的HIV-HCV基因型1合并感染的复发患者中显示出较高的SVR24率。

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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.

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.

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来源期刊

HIV Clinical Trials 医学-传染病学

CiteScore

1.76

自引率

0.00%

发文量

审稿时长

>12 weeks

期刊介绍： HIV Clinical Trials is devoted exclusively to presenting information on the latest developments in HIV/AIDS clinical research. This journal enables readers to obtain the most up-to-date, innovative research from around the world.