Initial outcomes of integrated community-based hepatitis C treatment for people who inject drugs: Findings from the Queensland Injectors’ Health Network

BackgroundIntegrated treatment and harm reduction services provide a unique opportunity to facilitate direct-acting antiviral (DAA) therapy for hepatitis C virus (HCV)-infected people who inject drugs (PWID). We examine outcomes of community-based delivery of DAA therapy for PWID.MethodsThe Queensland Injectors’ Health Network (QuIHN) is a community-based agency providing harm reduction and treatment services. Data (including current injecting, involvement in opioid substitution therapy and other treatment, level of case management support) for participants initiating DAA therapy were collected. The primary endpoint was sustained virological response at 12 weeks (SVR) after the end of therapy.ResultsBy the end of February 2017, 127 treatment clients who consented for research had completed therapy and were due for post-treatment sustained virological response (SVR) testing. In an intent-to-treat analysis, 96% completed their course of prescribed treatment, 80% had confirmed SVR and 92% adhered to treatment. There were no confirmed cases of treatment non-response. The clients without confirmed SVR (20%) had not attended their post-treatment test. No client characteristics, including involvement in less-than-daily (odds ratio (OR) 0.27, 95% confidence interval (CI): 0.06–1.17) or daily injecting drug use (OR 0.65, 95% CI: 0.17–2.43) were associated with non-attendance at the SVR test.ConclusionPWID can be effectively treated for HCV and comply with DAA therapy in an integrated community-based service. However, strategies are required to support client retention until SVR is confirmed.     

Interventions to prevent HIV and Hepatitis C in people who inject drugs: A review of reviews to assess evidence of effectiveness

BackgroundInjecting drug use is a major risk factor for the acquisition and transmission of HIV and Hepatitis C virus (HCV). Prevention of these infections among people who inject drugs (PWID) is critical to reduce ongoing transmission, morbidity and mortality.MethodsA review of reviews was undertaken involving systematic literature searches of Medline, Embase, CINAHL, PsychINFO, IBSS and the Cochrane Library (2000–2011) to identify English language reviews regarding the effectiveness of harm reduction interventions in relation to HIV transmission, HCV transmission and injecting risk behaviour (IRB). Interventions included needle and syringe programmes (NSP); the provision of injection paraphernalia; opiate substitution treatment (OST); information, education and counselling (IEC); and supervised injecting facilities (SIFs). Reviews were classified into ‘core’ or ‘supplementary’ using critical appraisal criteria, and the strength of review-level evidence was assessed.ResultsTwelve core and thirteen supplementary reviews were included. From these reviews we identified: (i) for NSP: tentative review-level evidence to support effectiveness in reducing HIV transmission, insufficient review-level evidence relating to HCV transmission, but sufficient review-level evidence in relation to IRB; (ii) for OST: sufficient review-level evidence of effectiveness in relation to HIV transmission and IRB, but tentative review-level evidence in relation to HCV transmission; (iii) for IEC, the provision of injection paraphernalia and SIFs: tentative review-level evidence of effectiveness in reducing IRB; and either insufficient or no review-level evidence for these interventions in relation to HIV or HCV transmission.ConclusionReview-level evidence indicates that harm reduction interventions can reduce IRB, with evidence strongest for OST and NSP. However, there is comparatively little review-level evidence regarding the effectiveness of these interventions in preventing HCV transmission among PWID. Further studies are needed to assess the effectiveness and impact of scaling up comprehensive packages of harm reduction interventions to minimise HIV and HCV transmission among PWID.     

Initiating HCV treatment with direct acting agents in opioid agonist treatment: When to start for people co-infected with HIV?

BackgroundDirect acting antivirals (DAA) raise the possibility of eliminating Hepatitis C virus (HCV) among people who inject drugs (PWID). However, concerns regarding treatment retention and reinfection challenge implementation efforts. Opioid agonist treatment (OAT) provides an opportunity to engage HCV-positive PWID into DAA-based treatment. Our objective was to identify when OAT adherence sufficiently improved to inform DAA initiation in OAT settings, assuming continuous OAT retention for at least twelve weeks is necessary to complete the DAA treatment course.MethodsThis was a retrospective cohort study of HCV/HIV co-infected PWID from a population-level linked administrative database of people diagnosed and living with HIV in British Columbia, Canada between 01/1996 and 12/2013. We used monthly follow-up data after initial OAT entry and considered the effects of demographics, disease severity, and HIV and OAT treatment characteristics over time on the probability of subsequent OAT retention of ≥12 weeks, and ≥8 weeks for sensitivity analysis. We fit a generalized linear mixed model to the overall study population, and on stratified samples of those continuously engaged on combination antiretroviral therapy (≥95% ART adherence). A set of monthly indicator variables (months 1, …, 7, >7) were included to fulfil the study objective.ResultsOur study included 1427 HCV/HIV co-infected PWID (39.0% female, 68.8% OAT-naïve). The odds of subsequent twelve-week retention in OAT were statistically significantly greater in month 3 versus month 1 (adjusted odds ratio: 1.18; 95% confidence interval: 1.02, 1.37); and the odds of subsequent 8-week retention in OAT were statistically significantly greater in month 2 versus month 1 (1.15, 95% CI: 1.02, 1.31). Among continuously ART-adherent individuals, the odds of subsequent twelve-week retention were not statistically significantly greater than in month 1 (month 2: 1.12 (0.82, 1.51); month 3: 1.08 (0.79, 1.47); month 4: 1.24 (0.91, 1.71)).ConclusionWe provide evidence that among HCV/HIV co-infected PWID, those retained in OAT for three or more months had higher odds of completing an additional twelve weeks of OAT, compared to no difference in those already receiving ART. These data may have implications for adherence to DAA therapy and further studies are needed to understand the optimal timing of DAA therapy in PWID receiving and not receiving OAT.     

Delivering direct acting antiviral therapy for hepatitis C to highly marginalised and current drug injecting populations in a targeted primary health care setting

BackgroundThe Kirketon Road Centre (KRC) is a community-based public health facility in Sydney, Australia, that provides healthcare to people who inject drugs (PWID), including hepatitis C virus (HCV) treatment. From March 2016, the Australian Government has provided access to direct-acting antivirals (DAA) for adults with chronic HCV, without liver disease stage or drug and alcohol use restrictions. The aim of this study was to report DAA treatment outcomes among highly marginalised PWID treated at KRC.MethodsAll individuals initiating DAA treatment at KRC and due for sustained virological response (SVR12) testing by end 2016 were included. Demographic, drug use behaviour, clinical parameters, adherence support and HCV treatment outcomes, including SVR12 were recorded. Factors associated with SVR12, loss-to-follow-up (LTFU) and delayed SVR12 testing (>SVR16) were assessed by multivariate analysis. SVR12 was assessed by intention-to-treat (ITT) and modified ITT, the latter excluding individuals with an end-of-treatment response (ETR) but no SVR12 assessment, or who postponed their SVR12 date due to treatment interruption.ResultsA total of 72 individuals commencing DAAs were included, of whom 67% were male, 30% homeless, and 32% Aboriginal. All had a lifetime history of injecting drug use, with 75% having injected within the last six months, and 44% injecting at least weekly; 25% were also enrolled in opioid substitution therapy. Twenty-five (35%) individuals elected to receive an enhanced adherence-support package. Fifty-nine of 72 (82%) individuals due for SVR12 attended for testing, of whom 59/59 (100%) achieved SVR, providing an ITT SVR of 82%. A further six individuals had undetectable HCV RNA at ETR, but no SVR12 assessment, and one interrupted treatment, providing a mITT SVR of 91%. Homelessness was associated with delayed SVR12 testing (OR 24.9 95%CI 2.9–212.8, p = 0.003). There was no association between LTFU and frequency of drug injection, last drug injected, or planned treatment duration.ConclusionThis study confirms that PWID can be successfully treated for HCV in a real-world setting using an integrated primary health care model. It also demonstrates feasibility to upscale DAA therapy in high-risk PWID populations, with potential individual and population-level public health benefits. Enhanced efforts are required to optimise post-treatment follow-up.     

Does informing people who inject drugs of their hepatitis C status influence their injecting behaviour? Analysis of the Networks II study

BackgroundPeople who inject drugs (PWID) are at risk of hepatitis C virus (HCV). It is plausible that PWID who receive a diagnosis of HCV will reduce their injecting risk out of concern for their injecting partners, although evidence for this is currently limited. The aim of this study was to investigate whether informing PWID of their HCV diagnosis was associated with a change in injecting behaviour.MethodsProspective, longitudinal study of PWID recruited from street drug markets across Melbourne, Australia. Interviews and HCV testing were conducted at 3-monthly intervals. The association between receiving a diagnosis of HCV and (i) injecting frequency and (ii) injecting equipment borrowing, was examined using generalized estimating equations (GEE) analysis.ResultsThirty-five individuals received a diagnosis of HCV during the study period. Receiving a diagnosis of HCV was associated with a decrease of 0.35 injections per month (p = 0.046) but there was no change in injecting equipment borrowing (p = 0.750).ConclusionsA small reduction in injecting frequency was observed in PWID who received a diagnosis of HCV. This finding should be investigated further in larger studies examining a wider range of injecting risk behaviours.     

Safety and efficacy of glecaprevir/pibrentasvir in patients with chronic hepatitis C genotypes 1–6 receiving opioid substitution therapy

BackgroundInternational guidelines recommend treatment of hepatitis C virus (HCV) infection in people who inject drugs (PWID), including those on opioid substitution therapy (OST). The pangenotypic combination of glecaprevir and pibrentasvir has shown high sustained virologic response at post-treatment Week 12 (SVR12) in clinical trials. Herein, we evaluate the safety and efficacy of glecaprevir/pibrentasvir in patients receiving OST.MethodsPooled data from patients with HCV genotypes 1–6 who were treated with glecaprevir/pibrentasvir for 8, 12, or 16 weeks in eight Phase 2 and 3 trials were categorized by use of OST. Treatment completion, treatment adherence, SVR12, adverse events (AEs), and laboratory abnormalities were evaluated for patients receiving and not receiving OST.ResultsAmong 2256 patients, 157 (7%) were receiving OST. Compared with patients not receiving OST, OST patients were younger (mean age, 46.8 vs 52.8 years), male (69% vs 54%), white (93% vs 80%), HCV treatment-naïve (86% vs 72%), had HCV genotype 3 (60% vs 26%), and had a history of depression or bipolar disorder (43% vs 19%). Most patients completed (OST: 98% [n/N = 154/157]; non-OST: 99% [n/N = 2070/2099]) and were adherent (received ≥90% of study drug doses) to glecaprevir/pibrentasvir treatment (OST: 98% [n/N = 121/123]; non-OST: 99% [n/N = 1884/1905] among patients with available data). In the intention-to-treat population, SVR12 rates in OST and non-OST patients were 96.2% (n/N = 151/157; 95% CI 93.2–99.2) and 97.9% (n/N = 2055/2099; 95% CI 97.3–98.5), respectively. For OST patients, reasons for nonresponse included virologic relapse (<1%; n = 1), premature study drug discontinuation (<1%; n = 1), and loss to follow-up (3%; n = 4). AEs occurring in ≥10% of OST patients were headache, fatigue, and nausea. Drug-related serious AEs, AEs leading to study drug discontinuation, and Grade 3 or higher laboratory abnormalities were infrequent in both groups (<1%). No HCV reinfections occurred through post-treatment Week 12.ConclusionGlecaprevir/pibrentasvir is highly efficacious and well tolerated in HCV-infected patients receiving OST.     

Changes in risk behaviours during and following treatment for hepatitis C virus infection among people who inject drugs: The ACTIVATE study

BackgroundThe risk of hepatitis C virus (HCV) reinfection due to continued injecting risk behaviours might remain a barrier to HCV treatment among people who inject drugs. We aimed to evaluate changes in risk behaviours during and following HCV treatment among people with ongoing injecting drug use or receiving opioid substitution treatment (OST).MethodsACTIVATE was an international multicentre clinical trial conducted between 2012 and 2014. Participants with HCV genotypes 2/3 infection were treated with peg-interferon/ribavirin for 12 or 24 weeks and completed a self-administered behavioural questionnaire at each study visit. The impact of time in treatment and follow-up on longitudinally measured recent (past month) behavioural outcomes was evaluated using generalized estimating equations.ResultsAmong 93 enrolled participants (83% male, median age 41 years), 55 (59%) had injected in the past month. Any injecting drug use decreased during HCV treatment and follow-up (OR 0.89 per incremental study visit; 95% CI 0.83–0.95). No significant changes were found in ≥daily injecting (OR 0.98; 95% CI 0.89–1.07), use of non-sterile needles (OR 0.94; 95% CI 0.79–1.12), sharing of injecting paraphernalia (OR 0.87; 95% CI 0.70–1.07) or non-injecting drug use (OR 1.01; 95% CI 0.92–1.10). Hazardous alcohol use decreased throughout (OR 0.56; 95% CI 0.40–0.77) and OST increased between enrolment and end of treatment (OR 1.48; 95% CI 1.07–2.04).ConclusionsRecent injecting drug use and hazardous alcohol use decreased, while OST increased during and following HCV treatment among participants with ongoing injecting drug use. These findings support further expansion of HCV care among PWID.     

Client and staff experiences of a co-located service for hepatitis C care in opioid substitution treatment settings in New South Wales,Australia

Background

Internationally, there are ongoing efforts to increase access to hepatitis C (HCV) assessment and treatment to counter a generally low uptake of treatment among people with a history of injecting drug use. The aim of this qualitative study was to examine client and staff attitudes towards and experience of co-location of HCV and opioid substitution treatment (OST) services.

Methods

In-depth interviews were conducted with 57 clients and 19 staff from four NSW clinics participating in the Australian ETHOS study.

Results

Client and staff participants typically welcomed integrated treatment, citing issues of convenience, reduced travel time and costs, persistent cues to engagement and immediacy of access to care. Positive attitudes towards the initiative were expressed even by clients who had not engaged with HCV care. Providing co-located care largely avoided the negative, stigmatising or discriminatory experiences that participants reported encountering in settings less familiar with people who use drugs. A minority of client participants expressed concerns about the lack of privacy and/or confidentiality available in the co-located model, preferring to seek HCV care elsewhere.

Conclusions

The co-location of HCV care in OST clinics was welcomed by the large majority of participants in this study. Besides issues of convenience, the appeal of the co-located service centred on the familiarity of existing relationships between clients and staff in the OST setting. While some clients remained distrustful of OST and chose not to take up HCV care in this setting, the co-located treatment model was overwhelmingly successful amongst both client and staff participants.