From the University of California, San Diego, La Jolla (D.L.W.), Ruane Medical and Liver Health Institute (P.J.R.), the Jeffrey Goodman Clinic, Los Angeles LGBT Center (C.H.), and Southern California Men's Medical Group-Men's Health Foundation (A.M.), Los Angeles, the University of California, San Francisco, San Francisco (A.L.), Veterans Affairs Long Beach Healthcare System, Long Beach (T.R.M.), and Pacific Oaks Medical Group, Beverly Hills (A.S.) - all in California; Johns Hopkins University, Lutherville, MD (M.S.S.); Icahn School of Medicine at Mount Sinai, New York (D.D.); University of Cincinnati College of Medicine, Cincinnati (K.E.S.); Infectious Disease Specialists of Atlanta, Decatur, GA (R.D.); MedStar Washington Hospital Center (D.F.), Whitman-Walker Health (S.H.), and Capital Medical Associates (B.R.) - all in Washington, DC; the Cure C Consortium, Houston (J.C.G.), and Tarrant County Infectious Disease Associates, Fort Worth (C.M.) - both in Texas; Orlando Immunology Center, Orlando (F.H.), and Midway Immunology and Research Center, Fort Pierce (M.R.) - both in Florida; the University of Alabama at Birmingham, Birmingham (E.T.O.); the University of Colorado, Denver (G.R.); Lehigh Valley Health Network, Allentown, PA (J.Y.); and Bristol-Myers Squibb, Wallingford, CT (F.M., P.D.Y., P.A.), and Princeton, NJ (Z.L., E.H., S.N.).
N Engl J Med. 2015 Aug 20;373(8):714-25. doi: 10.1056/NEJMoa1503153. Epub 2015 Jul 21.
The combination of daclatasvir, a hepatitis C virus (HCV) NS5A inhibitor, and the NS5B inhibitor sofosbuvir has shown efficacy in patients with HCV monoinfection. Data are lacking on the efficacy and safety of this combination in patients coinfected with human immunodeficiency virus type 1 (HIV-1).
This was an open-label study involving 151 patients who had not received HCV treatment and 52 previously treated patients, all of whom were coinfected with HIV-1. Previously untreated patients were randomly assigned in a 2:1 ratio to receive either 12 weeks or 8 weeks of daclatasvir at a standard dose of 60 mg daily (with dose adjustment for concomitant antiretroviral medications) plus 400 mg of sofosbuvir daily. Previously treated patients were assigned to undergo 12 weeks of therapy at the same doses. The primary end point was a sustained virologic response at week 12 after the end of therapy among previously untreated patients with HCV genotype 1 who were treated for 12 weeks.
Patients had HCV genotypes 1 through 4 (83% with genotype 1), and 14% had compensated cirrhosis; 98% were receiving antiretroviral therapy. Among patients with genotype 1, a sustained virologic response was reported in 96.4% (95% confidence interval [CI], 89.8 to 99.2) who were treated for 12 weeks and in 75.6% (95% CI, 59.7 to 87.6) who were treated for 8 weeks among previously untreated patients and in 97.7% (95% CI, 88.0 to 99.9) who were treated for 12 weeks among previously treated patients. Rates of sustained virologic response across all genotypes were 97.0% (95% CI, 91.6 to 99.4), 76.0% (95% CI, 61.8 to 86.9), and 98.1% (95% CI, 89.7 to 100), respectively. The most common adverse events were fatigue, nausea, and headache. There were no study-drug discontinuations because of adverse events. HIV-1 suppression was not compromised.
Among previously untreated HIV-HCV coinfected patients receiving daclatasvir plus sofosbuvir for HCV infection, the rate of sustained virologic response across all genotypes was 97.0% after 12 weeks of treatment and 76.0% after 8 weeks. (Funded by Bristol-Myers Squibb; ALLY-2 ClinicalTrials.gov number, NCT02032888.).
达卡他韦是一种丙型肝炎病毒（HCV）NS5A 抑制剂，与 NS5B 抑制剂索非布韦联合使用，已显示出对 HCV 单感染患者的疗效。然而，在 HIV-1 合并感染的患者中，联合使用这两种药物的疗效和安全性数据尚缺乏。
这是一项开放性标签研究，纳入了 151 例未接受 HCV 治疗的患者和 52 例既往接受治疗的 HIV-1 合并感染患者。所有患者均接受了达卡他韦（每日标准剂量 60mg，同时根据合并使用的抗逆转录病毒药物进行剂量调整）加索非布韦（每日 400mg）联合治疗。既往未接受治疗的患者随机按 2:1 的比例接受 12 周或 8 周的治疗。主要终点为初治患者接受 12 周治疗后，HCV 基因 1 型患者在治疗结束后第 12 周的持续病毒学应答率。
患者的 HCV 基因型为 1 至 4 型（83%为基因型 1），14%合并代偿性肝硬化；98%正在接受抗逆转录病毒治疗。在基因型 1 患者中，接受 12 周治疗的患者中，有 96.4%（95%置信区间 [CI]，89.8%至 99.2%）和接受 8 周治疗的患者中有 75.6%（95% CI，59.7%至 87.6%）达到持续病毒学应答，而既往接受治疗的患者中，接受 12 周治疗的患者有 97.7%（95% CI，88.0%至 99.9%）达到持续病毒学应答。所有基因型的持续病毒学应答率分别为 97.0%（95% CI，91.6%至 99.4%）、76.0%（95% CI，61.8%至 86.9%）和 98.1%（95% CI，89.7%至 100%）。最常见的不良反应是疲劳、恶心和头痛。没有因不良反应而停止使用研究药物。HIV-1 抑制不受影响。
在接受达卡他韦联合索非布韦治疗 HCV 感染的初治 HIV-HCV 合并感染患者中，所有基因型患者接受 12 周治疗的持续病毒学应答率为 97.0%，接受 8 周治疗的持续病毒学应答率为 76.0%。（由 Bristol-Myers Squibb 公司资助；ALLY-2 临床试验.gov 编号，NCT02032888。）
