Determining the effectiveness of harm reduction interventions in the prevention of hepatitis C virus transmission among people who inject drugs in Scotland

The hepatitis C virus (HCV) is highly prevalent among people who inject drugs (PWID) in Scotland and the large majority of new HCV infections occurring in Scotland are within this population group. Harm reduction interventions, mainly sterile injecting equipment provision (IEP) and opioid substitution treatment (OST), to prevent the transmission of blood-borne viruses among PWID, were implemented in Scotland in the late 1980s/early 1990s. More recently, government policy initiatives, particularly the Hepatitis C Action Plan for Scotland, have stipulated the scale-up of these interventions. The overarching aim of this thesis was to investigate the impact of harm reduction interventions on the transmission of HCV among PWID in Scotland. Five secondary objectives were addressed in order to fulfil the main aim: (i) to review the international literature on the effectiveness of IEP and OST in preventing HCV transmission; (ii) to determine the association between self-reported sharing of needles/syringes and incident/prevalent HCV infection; (iii) to determine the association between sharing non-needle/syringe injecting paraphernalia and incident HCV infection; (iv) to determine the incidence of HCV among PWID in Scotland; and (v) to determine the association between self-reported uptake of IEP/OST and incident HCV infection. To address the first thesis objective, a systematic review of the literature was undertaken to identify existing international research evidence (published up to March 2007) for the effectiveness of harm reduction interventions. While HCV was the main outcome of interest, HIV and injecting risk behaviour (IRB) were also considered. A review of reviews approach identified: insufficient evidence that sterile needle and syringe provision (NSP) was effective in preventing HCV transmission; tentative evidence that NSP was effective in preventing HIV transmission; sufficient evidence to support the effectiveness of NSP in reducing self-reported IRB; and little to no evidence on needle/syringe vending machines, outreach NSP or the provision of other injecting paraphernalia (spoons, filters, water) in relation to any of the outcomes. With regard to OST, the findings were: insufficient evidence to show that OST has an impact on HCV transmission; sufficient evidence to support the effectiveness of continuous OST in reducing HIV transmission; and sufficient evidence to support the effectiveness of OST in reducing IRB by reducing the frequency of injection, the sharing of injecting equipment and injecting risk scores. An update to the review of reviews was undertaken to include literature published through March 2011, and found that little changed as a result of additional published reviews: in the main, the evidence statement for the effectiveness of OST with regard to HCV was upgraded from insufficient to tentative. The finding of weaker evidence with regard to biological outcomes (e.g. HCV, HIV), as compared with behavioural outcomes, indicated that low levels of IRB may be insufficient to reduce high levels of transmission, particularly for HCV. The subsequent chapter aimed to address the second thesis objective, by summarising, and exploring factors that explained the variation in, the measure of association between self-reported sharing of needles/syringes and HCV prevalence/incidence among PWID. A systematic review and meta-analysis were undertaken to identify and combine the results of European studies of HCV prevalence (or incidence) among those who reported ever/never (or recent/non-recent) sharing of needles/syringes. Among the 16 cross-sectional studies and four longitudinal studies identified, the pooled prevalence of HCV was 59% among PWID who reported never sharing needles/syringes and the pooled incidence of HCV was 11% among PWID who reported not recently sharing needles/syringes. Random effects meta-analysis generated a pooled odds ratio (OR) of 3.3 (95% confidence interval [CI] 2.4-4.6), comparing HCV infection among those who ever (or recently) shared needles/syringes relative to those who reported never (or not recently) sharing. Differences in pooled ORs were found when studies were stratified by recruitment setting (prison vs. drug treatment sites), recruitment method (outreach vs. non-outreach), sample HCV prevalence and sample mean/median time since onset of injecting. High incidence/prevalence rates among those who did not report sharing needles/syringes during the risk period may be a result of a combination of unmeasured risk factors (such as sharing non-needle/syringe injecting paraphernalia) and reporting bias. Study design and population were found to be modifiers of the size and strength of association between HCV and needle/syringe-sharing. To address the third thesis objective, the risk of HCV associated with sharing injecting paraphernalia (spoons, filters and water) was investigated using data from the 2008-09 and 2010 sweeps in a series of national cross-sectional surveys of PWID in Scotland, collectively called the Needle Exchange Surveillance Initiative (NESI). Logistic regression was used to examine the association between recent HCV infection (anti-HCV negative and HCV-RNA positive individuals) and self-reported measures of injecting equipment sharing in the six months preceding interview. Twelve percent of the sample reported sharing needles/syringes and 40% reported sharing paraphernalia in the previous six months. The adjusted odds ratios (AORs) for sharing needles/syringes (with or without paraphernalia) and sharing only paraphernalia in the last six months were 6.7 (95% CI 2.6-17.1) and 3.0 (95% CI 1.2-7.5), respectively. Among those who reported not sharing needles/syringes, sharing spoons and sharing filters were significantly associated with recent HCV infection (AOR 3.1, 95% CI 1.3-7.8 and 3.1, 95% CI 1.3-7.5, respectively); sharing water was not. This cross-sectional approach to the analysis of the association between sharing paraphernalia and incident HCV infection demonstrated consistent results with previous longitudinal studies. The prevalence of paraphernalia-sharing in the study population was high, potentially representing a significant source of HCV transmission. Addressing the fourth and fifth thesis objectives, a method to determine the incidence of HCV among PWID using a cross-sectional design was applied, and the associations between self-reported uptake of harm reduction interventions (OST and IEP) and recent HCV infection were examined. This was undertaken on data from the first sweep (2008-09) of NESI. Twenty-four recent HCV infections (as defined above) were detected, yielding incidence rate estimates ranging from 10.8-21.9 per 100 person-years. After adjustment for confounders, those with high needle/syringe coverage had reduced odds of recent infection (AOR 0.32, 95% CI 0.10-1.00, p=0.050). In the Greater Glasgow and Clyde region only, there were reduced odds of recent infection among those currently receiving OST, relative to those on OST in the last six months but not currently (AOR 0.04, 95% CI 0.001-1.07, p=0.055). The effect of combined uptake of OST and high needle/syringe coverage was only significant in unadjusted analyses (OR 0.34, 95% CI 0.12-0.97, p=0.043; AOR 0.48, 95% CI 0.16-1.48, p=0.203). The final analysis chapter built on the previous chapter investigating the association between uptake of harm reduction interventions and recent HCV infection, by using data from three sweeps of the NESI survey, undertaken in 2008-09, 2010 and 2011-12. A framework to triangulate different types of evidence – ‘group-level/ecological’ and ‘individual-level’ – was applied. Data on service provision (injecting equipment provision and methadone dispensation) were also collated and analysed. 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. The approach to deriving estimates for incidence, and associated uncertainty ranges, was modified from that applied to the first sweep of NESI. A decline in HCV incidence, per 100 person-years, from 13.6 (95% CI 8.1-20.1) in 2008-09 to 7.3 (95% CI 3.0-12.9) in 2011-12 was observed, 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 also seen. Individual-level evidence demonstrated that combined OST and high coverage of needles/syringes 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 (AORw 0.05, 95% CI 0.01-0.18). There was no additional effect found for high paraphernalia coverage. The combination of harm reduction interventions may have averted an estimated 1,400 new HCV infections and 1,000 new chronic infections between 2008 and 2012. The body of work in this thesis represents a novel contribution to the evidence base: it was the first large-scale, national application of a method designed to determine incidence of HCV using a cross-sectional design, and the first study to apply a framework to triangulate the evidence from different designs in order to investigate the association between harm reduction interventions and HCV transmission. This thesis does not propose to be able to establish a definitive causal link between IEP/OST and the prevention of HCV transmission. It does, however, provide sufficiently plausible evidence that the scale-up of a combination of harm reduction interventions in Scotland between 2008 and 2012 contributed to the reduction in HCV incidence observed. Components of the thesis have already influenced existing policy and practice in Scotland and internationally. Regarding future policy in this area, the evidence generated and presented here supports, at least, the maintenance of the HCV prevention investment in Scotland, and certainly the consideration of further scale-up

Increased risk of HIV and other drug-related harms associated with injecting in public places: national bio-behavioural survey of people who inject drugs

Background: Whilst injecting drugs in public places is considered a proxy for high risk behaviour among people who inject drugs (PWID), studies quantifying its relationship with multiple drug-related harms are lacking and none have examined this in the context of an ongoing HIV outbreak (located in Glasgow, Scotland). We aimed to: 1) estimate the prevalence of public injecting in Scotland and associated risk factors; and 2) estimate the association between public injecting and HIV, current HCV, overdose, and skin and soft tissue infections (SSTI). Methods: Cross-sectional, bio-behavioural survey (including dried blood spot testing to determine HIV and HCV infection) of 1469 current PWID (injected in last 6 months) recruited by independent interviewers from 139 harm reduction services across Scotland during 2017–18. Primary outcomes were: injecting in a public place (yes/no); HIV infection; current HCV infection; self-reported overdose in the last year (yes/no) and SSTI the last year (yes/no). Multi-variable logistic regression was used to determine factors associated with public injecting and to estimate the association between public injecting and drug-related harms (HIV, current HCV, overdose and SSTI). Results: Prevalence of public injecting was 16% overall in Scotland and 47% in Glasgow city centre. Factors associated with increased odds of public injecting were: recruitment in Glasgow city centre (aOR=5.45, 95% CI 3.48–8.54, p<0.001), homelessness (aOR=3.68, 95% CI 2.61–5.19, p<0.001), high alcohol consumption (aOR=2.42, 95% CI 1.69–3.44, p<0.001), high injection frequency (≥4 per day) (aOR=3.16, 95% CI 1.93–5.18, p<0.001) and cocaine injecting (aOR=1.46, 95% CI 1.00 to 2.13, p = 0.046). Odds were lower for those receiving opiate substitution therapy (OST) (aOR=0.37, 95% CI 0.24 to 0.56, p<0.001) and older age (per year increase) (aOR=0.97, 95% CI 0.95 to 0.99, p = 0.013). Public injecting was associated with an increased risk of HIV infection (aOR=2.11, 95% CI 1.13–3.92, p = 0.019), current HCV infection (aOR=1.49, 95% CI 1.01–2.19, p = 0.043), overdose (aOR=1.59, 95% CI 1.27–2.01, p<0.001) and SSTI (aOR=1.42, 95% CI 1.17–1.73, p<0.001). Conclusions: These findings highlight the need to address the additional harms observed among people who inject in public places and provide evidence to inform proposals in the UK and elsewhere to introduce facilities that offer safer drug consumption environments

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

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 (AORw 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

Enhanced surveillance of COVID-19 in Scotland: population-based seroprevalence surveillance for SARS-CoV-2 during the first wave of the epidemic

This work was funded by the Scottish Government.Objectives: The impact of the COVID-19 pandemic in Scotland has been amongst the most severe in Europe. Serological surveillance is critical to determine the overall extent of infection across populations and to inform the public health response. This study aimed to estimate the proportion of people who have antibodies to SARS-CoV-2 ('seroprevalence') in the general population of Scotland and to see if this changes over time. Study Design/Methods: Between International Organization for Standardization (ISO) week 17 (i.e. week commencing 20th April) and ISO week 25 (week commencing 15 June), 4751 residual blood samples were obtained from regional biochemistry laboratories in six participating regional health authority areas covering approximately 75% of the Scottish population. Samples were tested for the presence of anti-SARS-CoV-2 IgG antibodies using the LIAISON®SARS-CoV-2 S1/S2 IgG assay (DiaSorin, Italy). Seroprevalence rates were adjusted for the sensitivity and specificity of the assay using Bayesian methods. Results: The combined adjusted seroprevalence across the study period was 4.3% (95% confidence interval: 4.2%-4.5%). The proportion varied each week between 1.9% and 6.8% with no difference in antibody positivity by age, sex or geographical area. Conclusions: At the end of the first wave of the COVID-19 pandemic, only a small fraction of the Scottish population had antibodies to SARS-CoV-2. Control of COVID-19 requires the ability to detect asymptomatic and mild infections that would otherwise remain undetected through existing surveillance systems. This is important to determine the true number of infections within the general population which, in turn, can help to understand transmission, inform control measures and provide a denominator for the estimation of severity measures such as the proportion of infected people who have been hospitalised and/or have died.PostprintPeer reviewe

Reduction in the population prevalence of hepatitis C virus viraemia among people who inject drugs associated with scale-up of direct-acting anti-viral therapy in community drug services:REAL WORLD DATA

BACKGROUND AND AIMS: There has been little empirical evidence to show the 'real-world' impact of scaling-up direct-acting anti-viral (DAA) treatment among people who inject drugs (PWID) on hepatitis C virus (HCV) viraemia at a population level. We aimed to assess the population impact of rapid DAA scale-up to PWID delivered through community services-including drug treatment, pharmacies, needle exchanges and prisons-in the Tayside region of Scotland, compared with Greater Glasgow and Clyde (GGC) and the Rest of Scotland (RoS). FINDINGS: Uptake of HCV therapy (last year) among PWID between 2013-14 and 2017-18 increased from 15 to 43% in Tayside, 6 to 16% in GGC and 11 to 23% in RoS. Between 2010 and 2017-18, the prevalence of HCV viraemia (among antibody-positives) declined from 73 to 44% in Tayside, 67 to 58% in GGC and 64 to 55% in RoS. The decline in viraemia was greater in Tayside [2017-18 adjusted odds ratio (aOR) = 0.47, 95% confidence interval (CI) = 0.30-0.75, P = 0.001] than elsewhere in Scotland (2017-18 aOR = 0.89, 95% CI = 0.74-1.07, P = 0.220) relative to the baseline of 2013-14 in RoS (including GGC). Per-protocol SVR rates among PWID treated in community sites did not differ from those treated in hospital sites in Tayside (97.4 versus 100.0%, P = 0.099). CONCLUSIONS: Scale-up of direct-acting anti-viral treatment among people who inject drugs can be achieved through hepatitis C virus (HCV) testing and treatment in community drug services while maintaining high sustained viral response rates and, in the Tayside region of Scotland, has led to a substantial reduction in chronic HCV in the population

Incarceration history and risk of HIV and hepatitis C virus acquisition among people who inject drugs: a systematic review and meta-analysis

Background People who inject drugs (PWID) experience a high prevalence of incarceration and might be at high risk of HIV and hepatitis C virus (HCV) infection during or after incarceration. We aimed to assess whether incarceration history elevates HIV or HCV acquisition risk among PWID. Methods In this systematic review and meta-analysis, we searched MEDLINE, Embase, and PsycINFO databases for studies in any language published from Jan 1, 2000 until June 13, 2017 assessing HIV or HCV incidence among PWID. We included studies that measured HIV or HCV incidence among community-recruited PWID. We included only studies reporting original results and excluded studies that evaluated incident infections by self-report. We contacted authors of cohort studies that met the inclusion or exclusion criteria, but that did not report on the outcomes of interest, to request data. We extracted and pooled data from the included studies using random-effects meta-analyses to quantify the associations between recent (past 3, 6, or 12 months or since last follow-up) or past incarceration and HIV or HCV acquisition (primary infection or reinfection) risk among PWID. We assessed the risk of bias of included studies using the Newcastle-Ottawa Scale. Between-study heterogeneity was evaluated using the I2 statistic and the P-value for heterogeneity. Findings We included published results from 20 studies and unpublished results from 21 studies. These studies originated from Australasia, western and eastern Europe, North and Latin America, and east and southeast Asia. Recent incarceration was associated with an 81% (relative risk [RR] 1·81, 95% CI 1·40–2·34) increase in HIV acquisition risk, with moderate heterogeneity between studies (I2=63·5%; p=0·001), and a 62% (RR 1·62, 95% CI 1·28–2·05) increase in HCV acquisition risk, also with moderate heterogeneity between studies (I2=57·3%; p=0·002). Past incarceration was associated with a 25% increase in HIV (RR 1·25, 95% CI 0·94–1·65) and a 21% increase in HCV (1·21, 1·02–1·43) acquisition risk. Interpretation Incarceration is associated with substantial short-term increases in HIV and HCV acquisition risk among PWID and could be a significant driver of HCV and HIV transmission among PWID. These findings support the need for developing novel interventions to minimise the risk of HCV and HIV acquisition, including addressing structural risks associated with drug laws and excessive incarceration of PWID

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