scaled-up levels of hepatitis C prevention and treatment interventions for people who inject drugs in three UK settings-what is required to achieve the WHO’s HCV elimination targets? Addiction (Abingdon,

Aims: We estimate the impact of existing high coverage needle and syringe provision (HCNSP, defined as obtaining more than one sterile needle and syringe per injection reported) and opioid substitution therapy (OST) on hepatitis C virus (HCV) transmission among people who inject drugs (PWID) in three United Kingdom (UK) settings. We determine required scale-up of interventions, including HCV treatment, needed to reach the World Health Organisation (WHO) target of reducing HCV incidence by 90% by 2030. Design HCV transmission modelling utilising UK empirical estimates for effect of OST and/or HCNSP on individual risk of HCV acquisition Setting Three UK cities with varying HCV antibody prevalence (Bristol 60%, Dundee 46%, Walsall 32%), OST (72-81%), and HCNSP coverage (28-56%). Measurements Relative change in new HCV infections over 2016-2030 if current interventions were stopped. Scale-up of HCNSP, OST and HCV treatment required to achieve the WHO elimination target. Findings Removing HCNSP or OST would increase the number of new HCV infections over 2016-2030 by 23-64% and 92-483%, respectively. Conversely, scaling-up these interventions to 80% coverage could achieve a 29% or 49% reduction in Bristol and Walsall, respectively, whereas Dundee achieves a 90% decrease in incidence with current levels of intervention because of existing high levels of HCV treatment (47-58 treatments per 1000 PWID). If OST and HCNSP are scaled-up, Walsall and Bristol can achieve the same impact by treating 14 or 40 per 1000 PWID annually, respectively (currently 1-3 and 6-12 treatments per 1000 PWID), while 18 and 43 treatments per 1000 PWID would be required if OST and HCNSP are not scaled-up. Conclusions Current opioid substitution therapy and high coverage needle and syringe provision coverage is averting substantial Hepatitis C transmission in the United Kingdom. Maintaining this coverage while initiating current injectors on treatment can reduce incidence by 90% by 2030. Introduction Hepatitis C virus (HCV) is a major cause of morbidity worldwide(1). Approximately 85% of HCV infections in the UK are acquired through injection drug use(2, 3), therefore prevention of HCV transmission among people who inject drugs (PWID) is crucial for reducing the HCV disease burden. Primary prevention interventions for HCV are opioid substitution therapy (OST) and needle and syringe programmes amongst PWID(4). OST and high coverage needle and syringe provision (HCNSP, defined as obtaining more than one sterile needle and syringe per injection) can reduce the risk of HCV acquisition by 40-80%(5-10). Although low in many settings(11, 12), UK coverage levels for OST (70%) and HCNSP (48%) are high(2). Further, the emergence of highly efficacious antiviral HCV drugs(13) has raised the possibility of scaling-up HCV treatment as a prevention strategy amongst PWID(14, 15). Consequently, the World Health Organisation (WHO) recently produced a global strategy for eliminating HCV(1). Modelling has suggested that OST and HCNSP has reduced HCV prevalence in the UK, but further scale-up will have limited impact(16), with HCV treatment being needed to markedly reduce HCV prevalence(15, 17, 18). However, no analyses have considered how the impact of OST or HCNSP may vary between regional settings, or what combined scale-up of HCV treatment with OST and HCNSP are required to achieve the WHO HCV-elimination targets. In this paper, a HCV transmission model incorporating improved empirical evidence for the effectiveness of harm reduction interventions is used to evaluate the impact of current levels of OST and HCNSP on cumulative number of incident HCV infections in three UK settings (Bristol, Dundee and Walsall), and the required scale-up of these interventions with HCV treatment to reach WHO’s targets of reducing HCV incidence by 90% by 2030(1).