Treatment Adherence and Support for People Who Inject Drugs Taking Direct-Acting Antiviral Therapy for Hepatitis C Infection

Phillip Read; Rosie Gilliver; John Kearley; Rebecca Lothian; Evan B. Cunningham; Karen J. Chronister; Gregory J. Dore


J Viral Hepat. 2019;26(11):1301-1310. 

In This Article


This study presents real-world data regarding adherence to DAA therapy amongst a highly marginalized population, with a majority (77%) currently injecting drugs or homeless. One-third of clients elected to receive daily or weekly enhanced adherence support. This support resulted in equivalent SVR12 testing and cure rates in the enhanced adherence support sub-population to the overall cohort of patients initiating treatment, despite of an over-representation of factors such as homelessness, Aboriginal identification, mental health diagnoses and daily injecting. The extension of therapy beyond the planned treatment duration in many clients with sub-optimal adherence improved overall adherence. These findings support the potential utility of this pragmatic model for enhancing DAA adherence amongst highly marginalized populations. The extremely low documented virological failure rate amongst clients with SVR12 assessment despite considerable doses missed and early discontinuations suggests relative "forgiveness" in relation to intermittent adherence.

Initial clinical trials have demonstrated high treatment adherence amongst people receiving OAT and those with recent injecting drug use.[11–14,24] Detailed analyses of adherence amongst recent PWID in the international SIMPLIFY study demonstrated high adherence to once-daily DAA therapy, although recent injecting of stimulants prior to and during treatment and variable timing of daily doses were associated with non-adherence.[25] These studies, however, are limited by the more structured clinical trial settings and methods to monitor adherence such as electronic blister packs may have acted as adherence support tools. DAA therapy broadens real-world and community-based studies of treatment adherence and outcomes amongst marginalized populations are crucial, particularly in the context of HCV elimination strategies.

In the enhanced adherence support sub-population of clients receiving daily or weekly dosing, median DAA adherence, as prescribed (86%) and with continued treatment (95%), was high. On-treatment adherence was 89%. This level of adherence is similar to clinical trial-based studies of recent PWID, although treatment completion (68%) was lower than the SIMPLIFY trial (97%).[24] The PREVAIL study conducted in OAT settings in the Bronx region of the United States randomized 51 participants to directly observed DAA therapy and demonstrated a similar adherence (86%) in this sub-group.[26]

In our study, high adherence (≥90%) was associated with earlier initiation of DAA therapy following launch of the Australian programme in March 2016. A very high uptake of DAA therapy was seen in the initial six months of the programme related to large "warehoused" populations in major liver disease and hepatitis tertiary care clinics,[27] but marginalized populations also clearly contain "early adopters" of DAA therapy who may be more motivated and/or have greater capacity to optimize adherence. Missing a dose within the initial four weeks of DAA therapy was associated with poorer adherence and therefore could allow early identification of clients who may benefit from enhanced adherence support. A large majority of clients in our study (91%) missed one of more doses during DAA therapy. The pattern of missed doses was variable, although episodes of missed doses were relatively short (median 1, IQR 1–2) and more likely to occur during the latter stages of planned treatment. In clients with sub-optimal adherence, the extension of therapy beyond the planned treatment duration increased overall on-treatment adherence from 86% to 95% and treatment completion of every tablet from 4% to 28%. Thus, a pragmatic and supportive approach enhanced adherence and no client with therapy completion (within the planned or extended duration) had documented virological failure. In fact, the only two clients with virological failure discontinued at weeks 2 and 5. Of interest, 5 of 6 clients who discontinued DAA therapy prior to week 4 and had SVR12 assessment were cured. Although other clients who discontinued prior to week 4 but without SVR12 assessment (n = 11) may have had virological failure, it does support evaluation of shorter duration therapeutic strategies. Higher levels of adherence in the early weeks of DAA therapy is further encouragement for such evaluation.

High loss to follow-up (29%) both during treatment and between treatment completion and SVR testing reflect challenges in this population. This loss to follow-up rate for SVR12 testing is similar to a larger sample of current PWID initiating DAA therapy in the Australian REACH-C study network (27%-35%),[28] but lower than reported in other real-world community cohorts in New York and the District of Columbia in the United States.[29–31] Further research and novel interventions are needed to identify effective ways to identify, engage and support clients during and after HCV treatment. Despite the potential individual health benefit of knowledge of treatment outcome, the population-level benefit of rapid DAA scale-up should be balanced against additional resources for contact and linkage to care post-treatment. Extremely high treatment efficacy amongst individuals who complete DAA therapy suggests efforts to optimize treatment completion are a priority, along with strategies to monitor high-risk individuals for HCV reinfection.

This study has several limitations. First, our measurement of adherence relied on the assumption that those clients (n = 30/79, 38%) who attended each week had been adherent for that week. As a result, adherence for these clients is likely overestimated. Conversely, doses while a client was in custody or hospital were only considered as having been taken if this could be confirmed with documentation included in the client's health record for all clients (daily or weekly dosing). Accordingly, adherence measurements for some clients may be lower than the actual adherence if documentation could not be obtained. Indeed, adherence in the self-managed sub-population could not be ascertained reliably to compare with those in the enhanced adherence support sub-population. Furthermore, this study was observational, and therefore, factors associated with enhanced adherence support may be subject to selection bias. Finally, this study was limited in relation to evaluation of the impact of extended therapy on virological outcome as there was no control group. In fact, favourable outcomes in several clients with very early discontinuation could argue against need for therapy extension.

In summary, we have demonstrated that amongst a highly marginalized population, a majority currently injecting drugs or homeless, there is a role for daily or weekly dosing support to enhance adherence and optimize treatment outcomes. Concerns that this population might have insufficient adherence to treatment to ensure virological cure appear unfounded, but overall adherence does decline over time in treatment. Despite this support, a high proportion of those treated did not test for cure at SVR12, and further efforts are required to understand and intervene in this scenario.

We recommend that individualized adherence support assessment is incorporated into HCV treatment programmes serving similar marginalized populations in order to optimize treatment outcomes and consequent HCV elimination.