Directly observed therapy of sofosbuvir/ribavirin +/− peginterferon with minimal monitoring for the treatment of chronic hepatitis C in people with a history of drug use in Chennai, India (C-DOT)

Background and Aims We assessed the feasibility of field-based directly observed therapy (DOT) with minimal monitoring to deliver HCV treatment to people with a history of drug use in Chennai, India. Methods 50 participants were randomized 1:1 to sofosbuvir + peginterferon alfa 2a + ribavirin (SOF+PR) for 12 weeks (Arm 1) vs. sofosbuvir + ribavirin (SOF+R) for 24 weeks (Arm 2). SOF+R was delivered daily at participant chosen venues and weekly peginterferon injections at the study clinic. HCV RNA testing was done to confirm active HCV infection and sustained virologic response 12 weeks after treatment completion (SVR12). No baseline genotyping or on-treatment viral loads were performed. Results Median age was 46 years. All were male and 10% had significant fibrosis/cirrhosis. All self-reported history of injection drug use, 18% recent non-injection drug use and 38% alcohol dependence. Six discontinued treatment (88% completed treatment in each arm). Of 22 who completed SOF+PR, all achieved SVR12 (22/25 = 88%); 15 of 22 who completed SOF+R achieved SVR12 (15/25 = 60%; p=0.05). Among those completing SOF+R, SVR12 was significantly less common among reporting ongoing substance use (36% vs. 100%) and missed doses. Active substance use and missed doses did not impact SVR with SOF+PR. Conclusions Field-based DOT of HCV therapy without real-time HCV RNA monitoring was feasible; however achieving 100% adherence was challenging. SOF+PR appeared superior to SOF+R in achieving SVR12, even when doses were missed with no discontinuations due to side effects. Further exploration of short duration treatment with peginterferon plus direct acting antivirals is warranted. This article is protected by copyright. All rights reserved.