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

Abstract

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.

Keywords: Epidemiology; Hepatology; INFECTIOUS DISEASES; Infection control; PUBLIC HEALTH; Public health.

Figure 1

Overview of HCV testing and treatment pathways for the PWID population in NHS Tayside. DBS, dried blood spot; HCV, hepatitis C virus; NHS, National Health Service; OST, opioid substitution treatment; PWID, people who inject drugs.

Figure 2

Trends in HCV antibody prevalence among PWID in Scotland and England 2010/2011 to 2016. HCV, hepatitisC virus; PWID, people who inject drugs.

Figure 3

Projected chronic HCV prevalence and incidence among PWID in Tayside with and without the intervention. Blue shaded area denotes the 95% credibility intervals of the model projections with and without the intervention. HCV, hepatitisC virus; PWID, people who inject drugs; py, person-years.

Figure 4

Causal impact synthetic control method (CIM) simulation and estimated intervention effects and 95% credible intervals for a range of assumed effects. Footnote: Illustration of CIM. First subplot shows a single data set, where solid lines represent the simulated prevalence in the absence of the intervention, and the dashed lines represent the outcome of treated site in the post-intervention period under different intervention magnitude scenarios. For each one of the three scenarios, we calculate the estimated average intervention effect along with credible intervals. These are shown in subplots 2 to 4. We see that as the effect increases, the intervals tend to move away for zero. However, the intervention effect only becomes significant in scenario 3, where zero is not included in any of the post-intervention time points.

Figure 5

Preliminary logic model HCV treatment as prevention (EPIToPe). HCPs, healthcare providers; HCV, hepatitis C virus; HCWs, healthcare workers; Hep-C, hepatitis C; NHS, National Health Service; NSP, needle and syringe programmes; TasP, Treatment as Prevention; PWID, people who inject drugs.