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Background  Government policy has precipitated recent changes in the provision of harm reduction interventions – injecting equipment provision (IEP) and opiate substitution therapy (OST) – for people who inject drugs (PWID) in Scotland. We sought to examine the potential impact of these changes on hepatitis C virus (HCV) transmission among PWID.    Methods and Findings  We used a framework to triangulate different types of evidence: ‘group-level/ecological’ and ‘individual-level’. Evidence was primarily generated from bio-behavioural cross-sectional surveys of PWID, undertaken during 2008-2012. Individuals in the window period (1–2 months) where the virus is present, but antibodies have not yet been formed, were considered to have recent infection. The survey data were supplemented with service data on the provision of injecting equipment and OST. Ecological analyses examined changes in intervention provision, self-reported intervention uptake, self-reported risk behaviour and HCV incidence; individual-level analyses investigated relationships within the pooled survey data. Nearly 8,000 PWID were recruited in the surveys. We observed a decline in HCV incidence, per 100 person-years, from 13.6 (95% CI: 8.1–20.1) in 2008–09 to 7.3 (3.0–12.9) in 2011–12; a period during which increases in the coverage of OST and IEP, and decreases in the frequency of injecting and sharing of injecting equipment, were observed. Individual-level evidence demonstrated that combined high coverage of needles/syringes and OST were associated with reduced risk of recent HCV in analyses that were unweighted (AOR 0.29, 95%CI 0.11–0.74) and weighted for frequency of injecting (AOR w  0.05, 95%CI 0.01–0.18). We estimate the combination of harm reduction interventions may have averted 1400 new HCV infections during 2008–2012.    Conclusions  This is the first study to demonstrate that impressive reductions in HCV incidence can be achieved among PWID over a relatively short time period through high coverage of a combination of interventions.

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Rapid Decline in HCV Incidence among People Who Inject Drugs Associated with National Scale-Up in Coverage of a Combination of Harm Reduction Interventions