RESUMO
Background & Aims: EASL guidelines recommend 8 weeks of treatment with sofosbuvir plus velpatasvir (SOF/VEL) for the treatment of acute or recently acquired HCV infection, but only 6- and 12-week data are available. Therefore, the aim of this study was to evaluate the safety and efficacy of a shortened 8-week SOF/VEL treatment for acute HCV monoinfection. Methods: In this investigator-initiated, prospective, multicentre, single-arm study, we recruited 20 adult patients with acute HCV monoinfection from nine centers in Germany. Patients received SOF/VEL (400/100 mg) as a fixed-dose combination tablet once daily for 8 weeks. The primary efficacy endpoint was the proportion of patients with sustained virological response 12 weeks after the end of treatment (SVR12). Results: The median HCV RNA viral load at baseline was 104,307 IU/ml; the distribution of HCV genotypes was as follows: GT1a/1b/2/3/4: n = 12/1/1/3/3. Thirteen (65%) of the 20 patients were taking medication for HIV pre-exposure prophylaxis. SVR12 was achieved in all patients who complied with the study protocol (n = 18/18 [100%], per protocol analysis), but the primary endpoint was not met in the intention-to-treat analysis (n = 18/20 [90%]) because two patients were lost to follow-up. One serious adverse event (unrelated to study drug) occurred during 12 weeks of post-treatment follow-up. Conclusions: The 8-week treatment with SOF/VEL was well tolerated and highly effective in all adherent patients with acute HCV monoinfection. Early treatment of hepatitis C might effectively prevent the spread of HCV in high-risk groups. Clinical Trial Number: NCT03818308. Impact and implications: The HepNet acute HCV-V study (NCT03818308), an investigator-initiated, single-arm, multicenter pilot study, demonstrates the efficacy and safety of 8 weeks of daily treatment with the fixed-dose combination sofosbuvir/velpatasvir (400/100 mg) in patients with acute hepatitis C virus (HCV) infection. All patients who completed therapy and were followed-up achieved sustained virologic response. Thus, early treatment with SOF/VEL which might effectively prevent the spread of HCV in high-risk groups can be recommended for patients with acute HCV monoinfection.
RESUMO
BACKGROUND: No published randomized controlled data on the use of direct-acting antivirals (DAA) in acute hepatitis C (AHC) coinfection exist. However, with the AHC epidemic ongoing among men who have sex with men (MSM) these are urgently needed. METHODS: The CHAT study is a randomized controlled trial of pegylated interferon + ribavirin (PR) plus telaprevir (TVR) for 12-24 weeks versus PR alone for 24-48 weeks in the response-guided treatment of patients with AHC genotype (GT) 1 infection and HIV-1 coinfection in Germany and Great Britain. RESULTS: 34 patients were included: 15 were randomized to the PR arm (arm 1), 19 to the TVR + PR arm (arm 2). All patients were MSM, median age was 40 years. 55% had IL28B C/C GT. Median baseline HCV RNA was 291,227 IU/ml, median alanine aminotransferase was 105 U/l. 85% received cART, all had baseline HIV RNA <40 copies/ml. Overall sustained virological response (SVR12) rate was 79.4% (27/34). SVR12 was seen in 12/15 (80%) in arm 1 and in 15/19 (79.8%) in arm 2. Of the four patients without SVR in arm 2, one experienced viraI breakthrough, two were non-responders; in one case HCV protease inhibitor (PI)-associated mutations were selected under TVR (V36M, R155K). CONCLUSIONS: Due to moderate response rates and additional toxicities 1st generation HCV PIs should not be used in treating acute HCV. While not being licensed, recent study data and guidelines support the use of dual DAA therapy but optimal treatment duration in acute HCV needs further investigation.
