Ledipasvir plus sofosbuvir fixed-dose combination for 6 weeks in patients with acute hepatitis C virus genotype 1 monoinfection (HepNet Acute HCV IV): an open-label, single-arm, phase 2 study

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• 作者：Katja Deterding ; MD^a ; ^c ; Christoph D Spinner ; MD^d ; Prof Eckart Schott ; MD^e ; Tania M Welzel ; MD^f ; Prof Guido Gerken ; MD^g ; Prof Hartwig Klinker ; MD^h ; Prof Ulrich Spengler ; MDⁱ ; Johannes Wiegand ; MD^j ; Julian Schulze zur Wiesch ; MD^k ; Anita Pathil ; MD^l ; Prof Markus Cornberg ; MD^a ; ^c ; ^m ; Andreas Umgelter ; MD^d ; Caroline Zö ; llner ; MD^e ; Prof Stefan Zeuzem ; MD^f ; Armin Papkalla ; PhDⁿ ; Kristina Weber ; PhD^b ; Svenja Hardtke ; PhD^c ; ^m ; Prof Heiko von der Leyen ; MDⁿ ; Prof Armin Koch ; PhD^b ; Dorothee von Witzendorff ; PhD^c ; Prof Michael P Manns ; MD^a ; ^c ; ^m ; ^{manns.michael@mh-hannover.de} ; Prof Heiner Wedemeyer ; MD^a ; ^c ; ^m ; ^{wedemeyer.heiner@mh-hannover.de} ; the HepNet Acute HCV IV Study Group^&dagger ;
• 刊名：The Lancet Infectious Diseases
• 出版年：2017
• 出版时间：February 2017
• 年：2017
• 卷：17
• 期：2
• 页码：215-222
• 全文大小：274 K
• 卷排序：17

文摘

Early treatment of acute hepatitis C virus (HCV) infection with interferon alfa is highly effective, but can be associated with frequent side-effects. We investigated the safety and efficacy of an interferon-free regimen for treatment of acute HCV infection.MethodsIn this prospective, open-label, multicentre, single-arm pilot study, we enrolled adults (≥18 years) with acute HCV genotype 1 monoinfection from ten centres in Germany. Patients were given ledipasvir (90 mg) plus sofosbuvir (400 mg) as a fixed-dose combination tablet once daily for 6 weeks. The primary efficacy outcome was the proportion of patients with sustained virological response (defined as undetectable HCV RNA 12 weeks after the end of treatment; other primary outcomes were safety and tolerability of ledipasvir plus sofosbuvir. The primary analysis population consisted of all patients who received at least one dose of study drug. Safety was also assessed in all patients who received at least one dose of the study drug. This trial is registered with ClinicalTrials.gov, number NCT02309918.FindingsBetween Nov 19, 2014, and Nov 10, 2015, we enrolled 20 patients. Median HCV RNA viral load at baseline was 4·04 log10 IU/mL (1·71–7·20); 11 patients were infected with HCV genotype 1a and nine patients with genotype 1b. All patients achieved a sustained virological response 12 weeks after the end of treatment (20 [100%] of 20 patients). Treatment was well tolerated; there were no drug-related serious adverse events. Up to 12 weeks after treatment, 22 possible or probable drug-related adverse events were reported. There was one serious adverse event, which was judged unrelated to the study drug; one patient was admitted to hospital for surgery of a ruptured cruciate ligament.InterpretationTreatment for 6 weeks with ledipasvir plus sofosbuvir was well tolerated and highly effective in patients with acute HCV genotype 1 monoinfection. Short-duration treatment of acute hepatitis C might prevent the spread of HCV in high-risk populations.FundingGilead Sciences, HepNet Study-House/German Liver Foundation, and German Centre for Infection Research (DZIF).