Adherence to sofosbuvir and velpatasvir among people with chronic HCV infection and recent injection drug use:The SIMPLIFY study

BACKGROUND:This study investigated treatment adherence among people with recent injecting drug use in a study of sofosbuvir/velpatasvir therapy for HCV infection. METHODS:SIMPLIFY is an international open-label, single-arm multicentre study that recruited participants with recent injecting drug use (previous six months) and chronic HCV genotype (G) 1-6 infection between March and October 2016 in seven countries (19 sites). Participants received sofosbuvir/velpatasvir once-daily for 12 weeks administered in a one-week electronic blister pack (records the time and date of each dose) for 12 weeks. We evaluated non-adherence (<90% adherent) as measured by electronic blister-pack assessed using logistic regression and generalised estimating equations (continuous) with detailed analyses of dosing dynamics. RESULTS:Among 103 participants, 97% (n = 100) completed treatment. Median adherence to therapy was 94%. Overall, 32% (n = 33) were considered non-adherent (<90% adherence). Adherence significantly decreased over the course of therapy. Recent stimulant injecting (cocaine and/or amphetamines) at treatment initiation and during treatment was independently associated with non-adherence. Inconsistent dose timing (standard deviation of daily dose timing of ≥240 min) was also independently associated with non-adherence to therapy. Factors associated with inconsistent dose timing included lower levels of education and recent stimulant injecting. SVR was similar among adherent and non-adherent populations (94% vs. 94%, P = 0.944). CONCLUSION:This study demonstrated high adherence to once-daily sofosbuvir/velpatasvir therapy among a population of people with recent injecting drug use. Recent stimulant injecting prior to and during DAA therapy and inconsistent dose-timing during treatment was associated with non-adherence. However, there was no impact of non-adherence on response to therapy, suggesting that adherence is not a significant barrier to successful DAA therapy in people with recent injecting drug use.Evan B.Cunningham, Janaki Amin, Jordan J.Feld, Julie Bruneau, Olav Dalgard, Jeff Powis ... et al

How to build trustworthy hepatitis C services in an opioid treatment clinic? A qualitative study of clients and health workers in a co-located setting

Background: Given the increasing burden of hepatitis C (HCV) related liver disease, innovative health care models are required to extend the reach of HCV care and treatment. Opioid substitution treatment (OST) clinics are places of high HCV prevalence. The OST clinic is a complex environment, quite distinct to other health care settings, with punitive regulations and practices, and a client population likely to be mistrustful of systems of authority. Nonetheless, trust is widely documented as essential to effective therapeutic encounters. This paper examines what is required to develop a trustworthy service in a place, the OST clinic, described by some critics as a site of "social control". Methods: In-depth interviews were conducted with 57 clients and 19 staff from four NSW pilot clinics participating in the Australian ETHOS study. Results: Interview data were examined using Hall's framework of trust, involving five principle domains: fidelity, competence, honest, confidentiality and global trust. 'Honesty' was found to be key to participants' establishing trust in the co-located service and its staff. However, the clinic site was also found to be a place of rationed trust, in which the themes of OST as "ruling peoples' lives" and the fear of repercussions resulting from perceived transgressions against clinic rules, threatened to over-ride or undermine the development of trust in HCV services. Client participants described trusting health workers "to a point". They expressed concerns about the fidelity of co-located HCV and OST services and described fears of "institutionalised lies" and breaches of confidentiality. Anxieties around the latter revealed a sense of "us and them" held by some clients, one in which health workers were perceived to "stick together" by putting their own interests before those of the clients. Discussion: Although the co-location of HCV and opioid treatments makes intuitive policy sense, HCV health workers in the OST space may be seen as representatives of a deeply mistrusted system. For the effective development of a trustworthy HCV care service, policy and practice activities are required to engender trust through clearly articulated explanations of service boundaries and the promotion of "success stories" through trusted peer networks

Adherence to response-guided pegylated interferon and ribavirin for people who inject drugs with hepatitis C virus genotype 2/3 infection: The ACTIVATE study

Background The aims of this analysis were to investigate treatment completion and adherence among people with ongoing injecting drug use or receiving opioid substitution therapy (OST) in a study of response-guided therapy for chronic HCV genotypes 2/3 infection. Methods ACTIVATE was a multicenter clinical trial recruited between 2012 and 2014. Participants with genotypes 2/3 were treated with directly observed peg-interferon alfa-2b (PEG-IFN) and self-administered ribavirin for 12 (undetectable HCV RNA at week 4) or 24 weeks (detectable HCV RNA at week 4). Outcomes included treatment completion, PEG-IFN adherence, ribavirin adherence, and sustained virological response (SVR, undetectable HCV RNA >12 weeks post-treatment). Results Among 93 people treated, 59% had recently injected drugs (past month), 77% were receiving OST and 56% injected drugs during therapy. Overall, 76% completed treatment. Mean on-treatment adherence to PEG-IFN and ribavirin were 98.2% and 94.6%. Overall, 6% of participants missed >1 dose of PEG-IFN and 31% took <95% of their prescribed ribavirin., Higher treatment completion was observed among those receiving 12 vs. 24 weeks of treatment (97% vs. 46%, P < 0.001) while the proportion of participants with 95% on-treatment ribavirin adherence was similar between groups (67% vs. 72%, P = 0.664). Receiving 12 weeks of therapy was independently associated with treatment completion. No factors were associated with 95% RBV adherence. Neither recent injecting drug use at baseline nor during therapy was associated with treatment completion or adherence to ribavirin. In adjusted analysis, treatment completion was associated with SVR (aOR 23.9, 95% CI 2.9–193.8). Conclusions This study demonstrated a high adherence to directly observed PEG-IFN and self-administered ribavirin among people with ongoing injecting drug use or receiving OST. These data also suggest that shortening therapy from 24 to 12 weeks can lead to improved treatment completion. Treatment completion was associated with improved response to therapy