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

Disclosures

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

In This Article

Results

In total, 242 KRC clients commenced DAA therapy for chronic HCV infection, 6 through early access schemes and 236 following initiation of the government-funded programme in March 2016. Demographic and clinical characteristics, stratified by inclusion in the enhanced adherence support sub-population are detailed in Table 1. Clients had a median age of 44 years, and 31% were female. Those in the enhanced adherence support sub-population (n = 79, 33%) were more likely to identify as Aboriginal (42% vs 18%, P = <.001), have experienced homelessness in the last 12 months (71% vs 36%, P < .001) and have a prior mental health diagnosis (71% vs 31% P < .001). Clients electing to receive enhanced adherence support were also more likely to have recently (within the last 6 months) injected (94% vs 65%, P < .001), to report injecting at least daily (24% vs 16% P < .001), to report poly-drug use (58% vs 47%, P < .001) and be currently enrolled in OAT (63% vs 33%, P < .01).

Major HCV genotypes were genotype 1 (55%) and genotype 3 (40%). Fibroscan® examination identified 12% (n = 29) with cirrhosis (F4 fibrosis/≥12.5 KpA). Viral co-infections were uncommon, with 7% (n = 16) HIV co-infected and 2% (n = 5) hepatitis B co-infected. DAA therapy choice and duration reflected both the distribution of genotypes and regimen availability in Australia, which occurred sequentially over the study period. In the full cohort of 242, 166 (69%) returned after 12 weeks for SVR testing, 70 (29%) were lost to follow-up by SVR12, and six (2%) died unrelated to treatment. All but two (164/166, 99%) of those tested were cured, giving an intent-to-treat SVR12 of 68%.

Treatment Support, Completion and Adherence

Amongst the 79 clients who received DAAs either daily or weekly at KRC and were included in the enhanced adherence support sub-population, the type of support provided, treatment completion, episodes of missed doses and adherence are described in Table 2. Amongst these clients, 54% (n = 43) attended daily to receive DAAs and OAT, 8% (n = 6) attended daily without receiving OAT and 38% (n = 30) attended weekly. Clients who chose daily over weekly dosing were more likely to be enrolled in OAT (84% vs 17%, P < .001), and to report poly-drug use (80% vs 53%, P = .022), there were no other significant differences between these groups. Sixty-eight per cent (n = 54) of clients completed treatment, 9% (n = 7) transferred elsewhere during treatment, 20% (n = 16) stopped attending and treatment was not fully completed, and two clients (2.5%) died unrelated to treatment. Reasons for loss to follow-up, when known, included moving from the area or clients prioritizing other needs over treatment.

Overall median adherence as prescribed was 86% (IQR: 71%-94%) during planned treatment duration and 95% (IQR: 80%-100%) incorporating extended dosing beyond the planned end of treatment date. Within the planned treatment duration, 30 clients (38%) had at least 90% adherence; with extended treatment, 52 clients (66%) had at least 90% adherence. Amongst clients who extended treatment (n = 42), the median additional days dosed was eight days (IQR: 5–11 days). Extending treatment also increased the proportion taking every intended dose from 4% to 28%. Figure 1 depicts daily adherence and treatment outcomes for each client in the enhanced adherence support sub-population. Periodic adherence over the course of treatment is described in Table 2.

Figure 1.

Daily adherence to DAAs, n = 79

Excluding doses missed after the client permanently discontinued treatment or was lost to follow-up, "on-treatment" adherence was 89% (IQR: 83%-95%).

Of the 79 clients enrolled in enhanced adherence support, 54 (68%) attended SVR12 test, of whom 52/54 (96%) were cured giving an intention-to-treat (ITT) SVR12 of 66% in this group, compared with 69% in the standard support model. The remaining 23 (29%) were lost to follow-up at the time of SVR12, and 2 (2.5%) had died. Amongst clients with SVR12 assessment, adherence <90% did not significantly impact virological outcome. There were two clients, however, with documented virological failure who received 2 and 5 weeks of treatment. Amongst all clients who discontinued therapy prior to week 4 (n = 17), 11 had no SVR12 assessment (including two who died), five were cured, and one had virological failure.

Episodes of Missed Doses

Seventy-two clients (91%) in the enhanced adherence support sub-population missed at least one dose during treatment with 39 (49%) missing a dose in the first two weeks of treatment and 17 (22%) first missing a dose during the third or fourth weeks of treatment. These 72 clients had a median of three episodes (IQR: 1–7 episodes) of missed dosing and a median length of each episode of one day (IQR: 1–2 days). The number of episodes was not significantly associated with any demographic or clinical characteristic.

Factors Associated With Adherence

Approximately one-third of clients (37%) in the enhanced adherence support sub-population had treatment adherence of at least 90% within the planned treatment duration (Table 3). In unadjusted logistic regression, months since the launch of the Australian DAA programme (1 March 2016) to treatment initiation and week of first missed dose were significantly associated with adherence of at least 90%. These factors maintained significance in adjusted analyses with later DAA initiation being associated with reduced odds of being adherent (aOR = 0.92, 95% CI: 0.84–0.99, P = .031) and first missed dose occurring after week 4 being associated with increased odds of being adherent (aOR = 4.59, 95% CI: 1.25–16.93, P = .022).

Generalized estimating equation methodology indicates that daily adherence declined over the course of treatment (per treatment week; OR 0.96, 95% CI 0.94–0.98, P < .001; Figure 2).

Figure 2.

Mean weekly adherence post DAA initiation. Data include weeks 1–8 for all participants. Week 9–12 data include only those prescribed 12 or 24 wk treatment. Post week 12 data for those prescribed 24 wk treatment are not shown due to small numbers

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