Infectious Diseases Department, Centre Hospitalo-Universitaire, and Unité Mixte de Recherche (UMR)1347, Université de Bourgogne, Dijon.
Institut National de la Santé et de la Recherche Médicale (INSERM) SC10-US019, Villejuif.
Clin Infect Dis. 2015 Sep 1;61(5):817-25. doi: 10.1093/cid/civ381. Epub 2015 May 14.
Few direct anti-hepatitis C virus (HCV) agents have been studied in difficult-to-treat null responder and cirrhotic human immunodeficiency virus (HIV)-coinfected patients. Daclatasvir and asunaprevir combined with pegylated interferon/ribavirin (peg-IFN/RBV) have shown promising results in HCV-monoinfected patients.
An open-label, single-arm, phase 2 study was conducted in HIV/HCV genotype 1/4-coinfected patients who were null responders to prior peg-IFN/RBV standard therapy and on a raltegravir-based regimen with HIV RNA <400 copies/mL. They received a 4-week lead-in phase with peg-IFN/RBV, followed by 24 weeks of asunaprevir (100 mg twice daily), daclatasvir (60 mg once daily), and peg-IFN/RBV. The primary endpoint was sustained virologic response 12 weeks after the end of treatment (SVR12) using intent-to-treat analysis.
Seventy-five patients were included, of whom 27 (36%) had cirrhosis. The median baseline CD4 count was 748 (interquartile range, 481-930) cells/µL. The global SVR12 rate was 96.0% (95% confidence interval [CI], 88.8%-99.2%; n = 72/75), 92.6% (95% CI, 75.7%-99.1%; n = 25/27) in cirrhotic patients, 94.6% (95% CI, 81.8%-99.3%; n = 35/37) in genotype 1 patients, and 97.4% (95% CI, 86.2%-99.9%; n = 37/38) in genotype 4 patients. Six patients (8%) stopped HCV therapy prematurely: 2 due to HCV breakthrough, 4 to adverse events (1 lung cancer, 3 infections). One patient with cirrhosis (with baseline platelet count <150 000 platelets/µL and albuminemia <35 g/L) died from multiorgan failure. Overall, 36 serious adverse events occurred in 21 (28%) patients. No HIV breakthrough was observed.
In HIV/HCV genotype 1/4-coinfected null responders, a 24-week regimen combining daclatasvir, asunaprevir, and peg-IFN/RBV was associated with a very high cure rate. The safety profile was acceptable, even though cirrhotic patients with low albuminemia and platelets should be monitored closely. This combination is a new option in this difficult-to-treat population.
NCT01725542.
在难以治疗的无应答者和肝硬化的人类免疫缺陷病毒（HIV）合并感染患者中，很少有直接抗丙型肝炎病毒（HCV）的药物被研究。达卡他韦和asunaprevir 联合聚乙二醇干扰素/利巴韦林（peg-IFN/RBV）在 HCV 单感染患者中显示出良好的效果。
在既往 peg-IFN/RBV 标准治疗无应答且 HIV RNA <400 拷贝/mL 的 HIV/HCV 基因型 1/4 合并感染患者中进行了一项开放性、单臂、2 期研究。他们接受了 4 周的 peg-IFN/RBV 导入期，随后接受 24 周的 asunaprevir（每日 2 次，每次 100mg）、达卡他韦（每日 1 次，每次 60mg）和 peg-IFN/RBV。主要终点是使用意向治疗分析治疗结束后 12 周的持续病毒学应答 12 周（SVR12）。
共纳入 75 例患者，其中 27 例（36%）有肝硬化。中位基线 CD4 计数为 748（四分位间距，481-930）细胞/µL。全球 SVR12 率为 96.0%（95%置信区间，88.8%-99.2%；n=72/75），27 例肝硬化患者中为 92.6%（95%置信区间，75.7%-99.1%；n=25/27），37 例基因型 1 患者中为 94.6%（95%置信区间，81.8%-99.3%；n=35/37），38 例基因型 4 患者中为 97.4%（95%置信区间，86.2%-99.9%；n=37/38）。6 例（8%）患者提前停止 HCV 治疗：2 例因 HCV 突破，4 例因不良反应（1 例肺癌，3 例感染）。1 例肝硬化患者（基线血小板计数<150000 个/µL 和白蛋白<35g/L）死于多器官衰竭。共有 36 例严重不良事件发生在 21 例（28%）患者中。未观察到 HIV 突破。
在 HIV/HCV 基因型 1/4 合并感染的无应答者中，联合使用达卡他韦、asunaprevir 和 peg-IFN/RBV 的 24 周治疗方案与非常高的治愈率相关。安全性特征可接受，尽管肝硬化患者白蛋白和血小板较低时应密切监测。该联合方案为这一难以治疗的人群提供了一种新的选择。
NCT01725542。
