Title: Evaluating the Population Impact of Hepatitis C Direct Acting Antivral Treatment as Prevention for People Who Inject Drugs (EPIToPe)
Funder: Department of Health and Social Care

Abstract: Our primary aim is to generate UK empirical evidence on the effectiveness of HCV &ldquo;Treatment as Prevention&ldquo; (TasP) in people who inject drugs (PWID). In Work-Stream (WS1) we will demonstrate that rapid large-scale HCV treatment can be delivered to PWID through community services. In WS2 we will enhance HCV surveillance among PWID to measure the population impact of the intervention. Through record-linkage, we will assess if HCV treatment leads to improved addiction treatment outcomes. In WS3 we will undertake a qualitative study to understand the barriers and facilitators to scaling-up community-based HCV treatment and patients accounts of addiction treatment that will form basis of a manual of how to scale-up HCV treatment for WS5. In WS4 we will develop synthetic control methods to quantify the TasP intervention effect and use dynamic transmission models to determine cost-effectiveness in the NHS. In WS5 we will co-design a trial of HCV TasP in PWID in England to provide definitive evidence for patients, clinicians and policy-makers. Background:- HCV is the second most important cause of liver cirrhosis in the UK and injecting drug use is the major risk factor among 200,000 people infected currently. Chronic HCV is still 40% among PWID, despite effective opioid substitution treatment (OST) and needle and syringe programmes (NSP). Modelling suggests that HCV treatment is essential to achieve substantial reductions in HCV prevalence and incidence among PWID. TasP is now possible with newer DAA therapies combining high cure rates (>90%) and short treatment duration (8-12 weeks). We have conducted a successful pilot study that showed we can increase case-finding and successfully treat PWID in the community. HCV treatment is expensive (&pound;12-40,000) so current NHS strategies restrict HCV treatment to people with moderate/severe disease, consequently few PWID (predominantly having mild disease) are treated. Therefore, we can evaluate HCV TasP in two ways. Firstly, we can conduct a non-randomised study of the impact of scaling-up HCV treatment to PWID (WS1-4). Secondly, if the current cost of HCV treatment falls, we will support HCV clinical leads to undertake a larger definitive evaluation of HCV TasP among PWID (WS5). Research plan:- In WS1 we scale-up HCV DAA treatment among PWID in NHS Tayside through existing services (NSP, OST centres, pharmacies and prisons) facilitated by community HCV nurse specialists. We will treat 500 PWID in two years which is projected to reduce chronic HCV prevalence from 29% to 10% (65% reduction) and incidence from 5% to 1.6%. Treatment response and re-infection rates will be monitored. In WS2 we support an extra Needle Exchange Surveillance Initiative (NESI) survey in Scotland (n=2500) and historical PCR testing (n=8000) of Unlinked Anonymous Monitoring Programme (UAM) in England to generate trends in chronic HCV outcomes in PWID from 2010 to 2021/22 for WS4&5. We use Multiple Parameter Evidence Synthesis methods to generate better estimates of PWID prevalence for WS4&5. We create a virtual cohort of 3600 PWID with information on HCV treatment, addiction treatment, and prison to test whether DAA treatment improves drug treatment outcomes and compare to WS3. In WS3 interviews with PWID (36-45) and focus groups (4) with service providers will explore perspectives on TasP; identify barriers and facilitators; and support a manual of how to scale-up HCV treatment in the community for WS5. Longitudinal interviews with 30-35 PWID successfully treated for HCV will assess whether their perspectives on addiction treatment and recovery alter. Trained peer researchers will be involved in data collection, analysis and dissemination. In WS4 we will model the effectiveness of the intervention in WS1, using outcomes measured in WS2. We will extend synthetic control methods to test for an intervention effect in NHS Tayside, with controls from the rest of the UK. Simulation exercises have shown that we have sufficient power to detect a 40% reduction in chronic HCV. We develop a dynamic transmission model using information collected in WS1 and WS2 to evaluate HCV TasP cost-effectiveness using real-world data, and estimate contribution of OST and NSP to TasP intervention effect. In WS5 we will support 22 HCV clinical networks to design and conduct an evaluation of HCV TasP in England. For example, a cluster RCT with 8600 extra HCV treatments randomised to 11 networks would have sufficient power to detect a reduction in chronic HCV of 25% which can be measured through the UAM in WS2. Strategies to increase scale-up will be assessed, informed by WS1 and WS3, and cost-effectiveness estimated using models from WS4. Patient and public involvement is integral to our Programme s design, conduct and dissemination. Our findings will have direct relevance to NHS and patients:- supporting services to prioritise PWID for early HCV treatment or focus more on minimising re-infection risk. We will generate multiple academic papers, present findings to practitioners and policy makers, and change and inform clinical guidance.

Lay abstract: Background: An estimated 200,000 people in the UK have been infected with the Hepatitis C Virus (HCV), which is an important cause of liver disease, cancer and death. Most HCV infections in the UK are in people who inject drugs. New HCV drugs cure over 90% of patients within 12 weeks with few side-effects, but are expensive (over &pound;20,000) and currently restricted to people with moderate or severe liver disease. Mathematical models suggest that HCV &ldquo;Treatment as Prevention&rdquo;, i.e. treating people who inject drugs and have mild liver disease for HCV, can reduce the overall number of new HCV infections in the population, even though some people who inject drugs may also become re-infected. Further, if HCV treatment is increased sufficiently, then HCV will eventually be &ldquo;eliminated&rdquo; from the UK population. However, the findings from these models need to be tested out in patients. &ndash; This is what we aim to address. Design: In the first study, our target is to treat at least 500 people who inject drugs in Dundee/ NHS Tayside over two years. This large rapid increase in HCV treatment will be delivered across multiple sites in the community, including pharmacies, addiction services, and prisons. We estimate that this will reduce chronic HCV in people who inject drugs in Dundee by two-thirds from nearly 30% to less than 10%. To measure changes in HCV in the population, we need to increase the data available from surveys of people who inject drugs in Tayside and the rest of the UK, and develop novel statistical methods that can provide unbiased estimates of whether HCV has changed over time. We will interview services providers in Dundee/NHS Tayside to identify key barriers and facilitators that can help other sites successfully scale-up HCV treatment. We will interview patients following treatment, and link to administrative databases to assess if being cured from HCV also helps people who inject drugs stay in specialist drug treatment and recover from addiction. We also will estimate whether the increase in HCV treatment to people who inject drugs is cost-effective to the NHS. Finally, as the number of HCV treatments increase in England, we will co-design a second and larger evaluation of HCV &ldquo;Treatment as Prevention&rdquo; with regional HCV clinical services. We will use evidence gathered from our first study to show how we can scale-up HCV treatment in the community, and determine whether HCV infections reduce more in sites with greater scale-up than in sites with less intense scale-up of HCV treatment. Dissemination: Our results will guide clinical practice and policy, and support decision-making by the NHS on whether people who inject drugs with mild liver disease should receive early treatment.

Research activity codes: 6.1 PHARMACEUTICALS;3.2 INTERVENTIONS TO ALTER PHYSICAL AND BIOLOGICAL ENVIRONMENTAL RISKS
Health categories: INFECTION;MENTAL HEALTH