Effectiveness of Ledipasvir-Sofosbuvir Combination in Patients With Hepatitis C Virus Infection and Factors Associated With Sustained Virologic Response

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• 作者：Norah A. Terrault¹ ; ^{norah.terrault@ucsf.edu} ; Stefan Zeuzem² ; Adrian M. Di Bisceglie³ ; Joseph K. Lim⁴ ; Paul J. Pockros⁵ ; Lynn M. Frazier⁶ ; Alexander Kuo⁷ ; Anna S. Lok⁸ ; Mitchell L. Shiffman⁹ ; Ziv Ben Ari¹⁰ ; Lucy Akushevich¹¹ ; Monika Vainorius¹¹ ; Mark S. Sulkowski¹² ; Michael W. Fried¹¹ ; David R. Nelson¹³ ; for the HCV-TARGET Study GroupDavid R. Nelson ; Michael W. Fried
• 关键词：DAA ; NS5A Inhibitor ; NS5B Inhibitor ; Antiviral
• 刊名：Gastroenterology
• 出版年：2016
• 出版时间：December 2016
• 年：2016
• 卷：151
• 期：6
• 页码：1131-1140.e5
• 全文大小：1460 K
• 卷排序：151

文摘

The combination of ledipasvir and sofosbuvir has been approved for treatment of genotype 1 hepatitis C virus (HCV) infection, including an 8-week regimen for treatment-naïve patients without cirrhosis and a baseline level of HCV RNA <6 million IU/mL. We analyzed data from a multicenter, prospective, observational study to determine real-world sustained virologic responses 12 weeks after treatment (SVR12) with regimens containing ledipasvir and sofosbuvir and identify factors associated with treatment failure.MethodsWe collected data from 2099 participants in the HCV-TARGET study with complete virologic data (per-protocol population). We analyzed data from 1788 patients receiving ledipasvir-sofosbuvir (282 for 8 weeks, 910 for 12 weeks, 510 for 24 weeks, and 86 for a different duration) and 311 receiving ledipasvir-sofosbuvir plus ribavirin (212 for 12 weeks and 81 for 24 weeks, 18 for other duration) to estimate SVR12 (with 95% confidence interval [CI]), and logistic regression methods to identify factors that predicted an SVR12.ResultsThe overall study population was 25% black, 66% with HCV genotype 1A infection, 41% with cirrhosis, 50% treatment-experienced, and 30% receiving proton pump inhibitors at start of treatment. In the per-protocol population, SVR12s were achieved by 96% of patients receiving ledipasvir-sofosbuvir for 8 weeks (95% CI, 93%−98%), 97% receiving the drugs for 12 weeks (95% CI, 96%−98%), and 95% receiving the drugs for 24 weeks (95% CI, 93%−97%). Among patients also receiving ribavirin, SVR12 was achieved by 97% of the patients receiving the drugs for 12 weeks (95% CI, 94%−99%) and 95% receiving the drugs for 24 weeks (95% CI, 88%−99%). Of the 586 patients who qualified for 8 weeks of treatment, only 255 (44%) received the drugs for 8 weeks. The rate of SVR12 among those who qualified for and received 8 weeks of therapy was similar in those who qualified for 8 weeks but received 12 weeks therapy (96%; 95% CI, 92%−99% vs 98%; 95% CI, 95%−99%). Factors that predicted SVR12 were higher albumin (≥3.5 g/dL), lower total bilirubin (≤1.2 g/dL), absence of cirrhosis, and absence of proton pump inhibitor use.ConclusionsRegimens containing ledipasvir and sofosbuvir are highly effective for a broad spectrum of patients with HCV genotype 1 infection treated in different clinical practice settings. Expanded use of 8-week treatment regimens for eligible patients is supported by these real-world results. Modification of proton pump inhibitor use may increase rates of SVR. ClinicalTrials.gov no. NCT01474811.