Hepatitis C Treatment As Prevention Pilot Study with Ledipasvir-Sofosbuvir Among People Actively Injecting Drugs (TasP-C Pilot)

Public Health Foundation Enterprises, City Of Industry CA

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Abstract

? DESCRIPTION (provided by applicant): This project is a randomized trial of two strategies to treat persons who currently inject drugs (PWIDs) with ledipasvir-sofosbuvir (LDV-SOF) for genotype 1 HCV. HCV is a major public health problem as infected persons are at risk of severe liver disease including fibrosis, cirrhosis and liver cancer, and incidence among PWIDs is as high as 26/100 person-years. High-quality syringe exchange and related activities may delay but have failed to substantially reduce HCV transmission. LDV-SOF is a once daily oral HCV medication with minimal toxicity and sustained viral response rate (SVR, equivalent to cure) of 94-100% for 8 weeks of treatment among treatment-naïve patients with genotype 1 HCV and no evidence of cirrhosis. This regimen obviates many of the barriers to HCV treatment for PWIDs, including regimen toxicity, duration, and dosing complexity, raising the prospect of Treatment as Prevention (TasP)-whereby PWIDs with chronic HCV infection could be treated to reduce forward HCV transmission. The potential impact of HCV therapy on HCV transmission in PWIDs has been explored in mathematical models demonstrating that treatment of chronic infection in PWIDs could reduce HCV prevalence and transmission. However, the feasibility of delivering HCV therapy to PWIDs who are actively injecting - the ideal target for a TasP initiative - is largely unknown. We propose to evaluate the feasibility and acceptability of modified directly observed treatment (mDOT) versus weekly dispensing with unobserved dosing of once daily LDV-SOF for 8 weeks to treat HCV among treatment- naïve, non-cirrhotic PWIDs with genotype 1 HCV. We will assess, through in-depth, semi-structured qualitative interviews, the challenges with time intensity required for mDOT and unobserved dosing interventions, and identify key factors affecting treatment adherence. We will randomize 30 treatment-naïve, non-cirrhotic PWIDs with genotype 1 HCV treated with once daily LDV-SOF to either mDOT or unobserved dosing, both with MI- based adherence support at weeks 0 and 4 of treatment, with 44 weeks of follow-up. Participants in the mDOT arm will be seen Mondays-Fridays during the first 8 weeks, while those in the unobserved dosing arm will be seen once a week. At first 8 weeks, serum samples will be collected and stored for sofosbuvir level testing for both arms, weekly. MI to enhance medication adherence will be administered at enrollment and week 4 for both conditions during first 8 weeks. Retention rates to visits, participation rates, and LDV-SOF adherence, therapy completion and sofosbuvir levels will be evaluated at week 8 (Aims 1 and 2). Qualitative interviews will be conducted at week 8 visit to evaluate challenges associated with treatment adherence and DOT / weekly dispensing procedures (Aim 3). HCV RNA testing will be conducted at weeks 4, 8, 20, and 44 to evaluate SVR, HCV relapse, and HCV reinfection, overall and by arm (Exploratory Aims). Audio Computer Administered Self Interview (ACASIs) will be conducted at enrollment, weeks 4, 8, 20, and 44 to collect social network and behavioral risk data (Exploratory Aims).