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
