在接受基因型耐药检测指导下，使用格拉瑞韦/依巴司韦联合或不联合利巴韦林治疗，人类免疫缺陷病毒/丙型肝炎病毒合并感染的男男性行为者获得高治愈率。
High Cure Rates With Grazoprevir-Elbasvir With or Without Ribavirin Guided by Genotypic Resistance Testing Among Human Immunodeficiency Virus/Hepatitis C Virus-coinfected Men Who Have Sex With Men.
机构信息
Division of Infectious Diseases and Hospital Epidemiology, University Hospital Zurich, University of Zurich, Switzerland.
Institute of Medical Virology, University of Zurich.
出版信息
Clin Infect Dis. 2019 Feb 1;68(4):569-576. doi: 10.1093/cid/ciy547.
BACKGROUND
This study was performed to investigate the efficacy and safety of grazoprevir-elbasvir guided by baseline resistance-associated substitutions (RASs) in the Swiss HCVree Trial.
METHODS
We performed hepatitis C virus (HCV) RNA screening among all men who have sex with men (MSM) enrolled in the Swiss HIV Cohort Study. Individuals with replicating HCV genotype 1 or 4 infection were eligible for grazoprevir-elbasvir treatment. Genotype 1a-infected individuals with baseline RASs and genotype 4-infected individuals with prior failure of HCV treatment received 16 weeks of grazoprevir-elbasvir combined with ribavirin. All other individuals received 12 weeks of grazoprevir-elbasvir alone. Patients reporting unprotected sex with occasional partners were offered a HCV risk reduction-oriented behavioral intervention.
RESULTS
We screened 3722 MSM and identified 177 (4.8%) with replicating infection. A total of 122 individuals (3.3%) were eligible for study treatment. Six of 76 patients infected with genotype 1a (7.3%) harbored baseline RASs. Sustained virological response after 12 weeks of follow-up was achieved in 121 patients (99%), including all with genotype 1a infection. Overall, 8 serious adverse events occurred, none of which was related to the study drug. Seventy-five percent of eligible MSM participated in the risk counseling program.
CONCLUSIONS
Grazoprevir-elbasvir for 12 or 16 weeks, with or without ribavirin, achieved high cure rates and had an excellent safety profile. Unique to other studies, the treatment duration was guided by the presence of baseline RASs among genotype 1a-infected individuals, and the treatment phase was accompanied by an HCV risk reduction-oriented behavioral intervention. This successful population-wide treatment approach lays the groundwork to achieve HCV elimination in coinfected MSM.
CLINICAL TRIALS REGISTRATION
NCT02785666.
背景
本研究旨在调查瑞士 HCVree 试验中基于基线耐药相关替代（RAS）的格拉瑞韦-艾尔巴韦治疗的疗效和安全性。
方法
我们对瑞士艾滋病毒队列研究中所有男男性行为者（MSM）进行了丙型肝炎病毒（HCV）RNA 筛查。具有复制性 HCV 基因型 1 或 4 感染的个体符合格拉瑞韦-艾尔巴韦治疗条件。基因型 1a 感染且基线存在 RAS 的个体以及既往 HCV 治疗失败的基因型 4 感染个体接受 16 周的格拉瑞韦-艾尔巴韦联合利巴韦林治疗。所有其他个体接受 12 周的格拉瑞韦-艾尔巴韦单药治疗。报告与偶尔性伴发生无保护性行为的患者接受 HCV 风险降低为导向的行为干预。
结果
我们筛查了 3722 名 MSM，发现 177 名（4.8%）具有复制性感染。共有 122 名个体（3.3%）符合研究治疗条件。76 名基因型 1a 感染患者中有 6 名（7.3%）存在基线 RAS。12 周随访后，121 名患者（99%）获得持续病毒学应答，包括所有基因型 1a 感染患者。总的来说，发生了 8 例严重不良事件，均与研究药物无关。75%的符合条件的 MSM 参加了风险咨询计划。
结论
格拉瑞韦-艾尔巴韦治疗 12 或 16 周，联合或不联合利巴韦林，实现了高治愈率，且具有极好的安全性。与其他研究不同的是，在基因型 1a 感染患者中，基于基线 RAS 确定治疗时间，且在治疗阶段伴随 HCV 风险降低为导向的行为干预。这种成功的全人群治疗方法为在合并感染的 MSM 中实现 HCV 消除奠定了基础。
临床试验注册
NCT02785666。
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