Evaluating the population impact of hepatitis C direct acting antiviral treatment as prevention for people who inject drugs (EPIToPe) - a natural experiment (protocol).

INTRODUCTION: Hepatitis C virus (HCV) is the second largest contributor to liver disease in the UK, with injecting drug use as the main risk factor among the estimated 200 000 people currently infected. Despite effective prevention interventions, chronic HCV prevalence remains around 40% among people who inject drugs (PWID). New direct-acting antiviral (DAA) HCV therapies combine high cure rates (>90%) and short treatment duration (8 to 12 weeks). Theoretical mathematical modelling evidence suggests HCV treatment scale-up can prevent transmission and substantially reduce HCV prevalence/incidence among PWID. Our primary aim is to generate empirical evidence on the effectiveness of HCV 'Treatment as Prevention' (TasP) in PWID. METHODS AND ANALYSIS: We plan to establish a natural experiment with Tayside, Scotland, as a single intervention site where HCV care pathways are being expanded (including specialist drug treatment clinics, needle and syringe programmes (NSPs), pharmacies and prison) and HCV treatment for PWID is being rapidly scaled-up. Other sites in Scotland and England will act as potential controls. Over 2 years from 2017/2018, at least 500 PWID will be treated in Tayside, which simulation studies project will reduce chronic HCV prevalence among PWID by 62% (from 26% to 10%) and HCV incidence will fall by approximately 2/3 (from 4.2 per 100 person-years (p100py) to 1.4 p100py). Treatment response and re-infection rates will be monitored. We will conduct focus groups and interviews with service providers and patients that accept and decline treatment to identify barriers and facilitators in implementing TasP. We will conduct longitudinal interviews with up to 40 PWID to assess whether successful HCV treatment alters their perspectives on and engagement with drug treatment and recovery. Trained peer researchers will be involved in data collection and dissemination. The primary outcome - chronic HCV prevalence in PWID - is measured using information from the Needle Exchange Surveillance Initiative survey in Scotland and the Unlinked Anonymous Monitoring Programme in England, conducted at least four times before and three times during and after the intervention. We will adapt Bayesian synthetic control methods (specifically the Causal Impact Method) to generate the cumulative impact of the intervention on chronic HCV prevalence and incidence. We will use a dynamic HCV transmission and economic model to evaluate the cost-effectiveness of the HCV TasP intervention, and to estimate the contribution of the scale-up in HCV treatment to observe changes in HCV prevalence. Through the qualitative data we will systematically explore key mechanisms of TasP real world implementation from provider and patient perspectives to develop a manual for scaling up HCV treatment in other settings. We will compare qualitative accounts of drug treatment and recovery with a 'virtual cohort' of PWID linking information on HCV treatment with Scottish Drug treatment databases to test whether DAA treatment improves drug treatment outcomes. ETHICS AND DISSEMINATION: Extending HCV community care pathways is covered by ethics (ERADICATE C, ISRCTN27564683, Super DOT C Trial clinicaltrials.gov: NCT02706223). Ethical approval for extra data collection from patients including health utilities and qualitative interviews has been granted (REC ref: 18/ES/0128) and ISCRCTN registration has been completed (ISRCTN72038467). Our findings will have direct National Health Service and patient relevance; informing prioritisation given to early HCV treatment for PWID. We will present findings to practitioners and policymakers, and support design of an evaluation of HCV TasP in England.

Association between universal hepatitis B prison vaccination, vaccine uptake and hepatitis B infection among people who inject drugs.

BACKGROUND AND AIMS: In Scotland, hepatitis B virus (HBV) vaccination for all prisoners was introduced in 1999; here, we examine the impact of this programme among people who inject drugs (PWID) in the community. This study aimed to compare rates of HBV vaccine uptake before and after implementation of the prison programme and to estimate the determinants of vaccine uptake, the levels of ever/current HBV infection and the associations between vaccine uptake and ever/current HBV infection. DESIGN: Data collected via serial cross-sectional surveys were used to compare the proportion who reported being vaccinated over time. For the 2013-14 survey, rates of ever/current HBV infection were calculated and the associations between vaccine uptake and ever/current HBV infection were examined using logistic regression. SETTING: Services providing injecting equipment and drug treatment and street sites in Glasgow (1993-2002) and throughout Scotland (2008-14). PARTICIPANTS: More than 10 000 PWID in total were recruited in the surveys. MEASUREMENTS: Participants completed a questionnaire (all years) to ascertain self-reported vaccine uptake and provided a blood spot (in 2013-14), tested for HBV core antibodies (anti-HBc) and surface antigen (HBsAg). FINDINGS: Among recent-onset PWID in Glasgow, vaccine uptake increased from 16% in 1993 to 59% in 2008-14 (P < 0.001). Among all PWID in Scotland, uptake increased further from 71% in 2008-09 to 77% in 2013-14 (P < 0.001) and was associated with incarceration [adjusted odds ratio (aOR) = 2.91, 95% confidence interval (CI) = 2.23-3.79]. The prevalence of anti-HBc and HBsAg in Scotland was 2.6 and 0.3%, respectively, among PWID who had commenced injecting in the decade since the programme's introduction. Vaccination was associated with reduced odds of ever (aOR = 0.60, CI = 0.37-0.97) and current (aOR = 0.40, CI = 0.16-0.97) HBV infection. CONCLUSIONS: In Scotland, uptake of hepatitis B virus (HBV) vaccination among people who inject drugs (PWID) in the community has increased since the 1999 introduction of universal prison vaccination, and current levels of HBV infection among PWID are low compared with other European countries.

Expansion of HCV treatment access to people who have injected drugs through effective translation of research into public health policy: Scotland's experience.

Seven years have elapsed since the Scottish Government launched its Hepatitis C Action Plan - a Plan to improve services to prevent transmission of infection, particularly among people who inject drugs (PWID), identify those infected and ensure those infected receive optimal treatment. The Plan was underpinned by industrial scale funding (around £100 million, in addition to the general NHS funding, will have been invested by 2015), and a web of accountable national and local multi-disciplinary multi-agency networks responsible for the planning, development and delivery of services. Initiatives ranged from the introduction of testing in specialist drug services through finger-prick blood sampling by non-clinical staff, to the setting of government targets to ensure rapid scale-up of antiviral therapy. The Plan was informed by comprehensive national monitoring systems, indicating the extent of the problem not just in terms of numbers infected, diagnosed and treated but also the more penetrative data on the number advancing to end-stage liver disease and death, and also through compelling modelling work demonstrating the potential beneficial impact of scaling-up therapy and the mounting cost of not acting. Achievements include around 50% increase in the proportion of the infected population diagnosed (38% to 55%); a sustained near two-and-a-half fold increase in the annual number of people initiated onto therapy (470 to 1050) with more pronounced increases among PWID (300 to 840) and prisoners (20 to 140); and reversing of an upward trend in the overall number of people living with chronic infection. The Action Plan has demonstrated that a Government-backed, coordinated and invested approach can transform services and rapidly improve the lives of thousands. Cited as "an impressive example of a national strategy" by the Global Commission on Drug Policy, the Scottish Plan has also provided fundamental insights of international relevance into the management of HCV among PWID.