Vivian Hope

The impact of needle and syringe provision and opiate substitution therapy on the incidence of Hepatitis C virus in injecting drug users: pooling of UK evidence.

AIMS To investigate whether opiate substitution therapy (OST) and needle and syringe programmes (NSP) can reduce hepatitis C virus (HCV) transmission among injecting drug users (IDUs). DESIGN Meta-analysis and pooled analysis, with logistic regression allowing adjustment for gender, injecting duration, crack injecting and homelessness. SETTING Six UK sites (Birmingham, Bristol, Glasgow, Leeds, London and Wales), community recruitment. PARTICIPANTS A total of 2986 IDUs surveyed during 2001-09. MEASUREMENT Questionnaire responses were used to define intervention categories for OST (on OST or not) and high NSP coverage (≥100% versus <100% needles per injection). The primary outcome was new HCV infection, measured as antibody seroconversion at follow-up or HCV antibody-negative/RNA-positive result in cross-sectional surveys. FINDINGS Preliminary meta-analysis showed little evidence of heterogeneity between the studies on the effects of OST (I2=48%, P=0.09) and NSP (I2=0%, P=0.75), allowing data pooling. The analysis of both interventions included 919 subjects with 40 new HCV infections. Both receiving OST and high NSP coverage were associated with a reduction in new HCV infection [adjusted odds ratios (AORs)=0.41, 95% confidence interval (CI): 0.21-0.82 and 0.48, 95% CI: 0.25-0.93, respectively]. Full harm reduction (on OST plus high NSP coverage) reduced the odds of new HCV infection by nearly 80% (AOR=0.21, 95% CI: 0.08-0.52). Full harm reduction was associated with a reduction in self-reported needle sharing by 48% (AOR 0.52, 95% CI: 0.32-0.83) and mean injecting frequency by 20.8 injections per month (95% CI: -27.3 to -14.4). CONCLUSIONS There is good evidence that uptake of opiate substitution therapy and high coverage of needle and syringe programmes can substantially reduce the risk of hepatitis C virus transmission among injecting drug users. Research is now required on whether the scaling-up of intervention exposure can reduce and limit hepatitis C virus prevalence in this population.

Hepatitis C Virus Infection Epidemiology among People Who Inject Drugs in Europe: A Systematic Review of Data for Scaling Up Treatment and Prevention

Background People who inject drugs (PWID) are a key population affected by hepatitis C virus (HCV). Treatment options are improving and may enhance prevention; however access for PWID may be poor. The availability in the literature of information on seven main topic areas (incidence, chronicity, genotypes, HIV co-infection, diagnosis and treatment uptake, and burden of disease) to guide HCV treatment and prevention scale-up for PWID in the 27 countries of the European Union is systematically reviewed. Methods and Findings We searched MEDLINE, EMBASE and Cochrane Library for publications between 1 January 2000 and 31 December 2012, with a search strategy of general keywords regarding viral hepatitis, substance abuse and geographic scope, as well as topic-specific keywords. Additional articles were found through structured email consultations with a large European expert network. Data availability was highly variable and important limitations existed in comparability and representativeness. Nine of 27 countries had data on HCV incidence among PWID, which was often high (2.7-66/100 person-years, median 13, Interquartile range (IQR) 8.7–28). Most common HCV genotypes were G1 and G3; however, G4 may be increasing, while the proportion of traditionally ‘difficult to treat’ genotypes (G1+G4) showed large variation (median 53, IQR 43–62). Twelve countries reported on HCV chronicity (median 72, IQR 64–81) and 22 on HIV prevalence in HCV-infected PWID (median 3.9%, IQR 0.2–28). Undiagnosed infection, assessed in five countries, was high (median 49%, IQR 38–64), while of those diagnosed, the proportion entering treatment was low (median 9.5%, IQR 3.5–15). Burden of disease, where assessed, was high and will rise in the next decade. Conclusion Key data on HCV epidemiology, care and disease burden among PWID in Europe are sparse but suggest many undiagnosed infections and poor treatment uptake. Stronger efforts are needed to improve data availability to guide an increase in HCV treatment among PWID.

Prevalence and estimation of hepatitis B and C infections in the WHO European Region: a review of data focusing on the countries outside the European Union and the European Free Trade Association

SUMMARY Knowledge of hepatitis B and C prevalence, and numbers infected, are important for planning responses. Published HBsAg and anti-HCV prevalences for the 20 WHO European Region countries outside the EU/EFTA were extracted, to complement published data for the EU/EFTA. The general population prevalence of HBsAg (median 3·8%, mean 5·0%, seven countries) ranged from 1·3% (Ukraine) to 13% (Uzbekistan), and anti-HCV (median 2·3%, mean 3·8%, 10 countries) from 0·5% (Serbia, Tajikistan) to 13% (Uzbekistan). People who inject drugs had the highest prevalence of both infections (HBsAg: median 6·8%, mean 8·2%, 13 countries; anti-HCV: median 46%, mean 46%, 17 countries), and prevalence was also elevated in men who have sex with men and sex workers. Simple estimates indicated 13·3 million (1·8%) adults have HBsAg and 15·0 million (2·0%) HCV RNA in the WHO European Region; prevalences were higher outside the EU/EFTA countries. Efforts to prevent, diagnose, and treat these infections need to be maintained and improved. This article may not be reprinted or reused in any way in order to promote any commercial products or services.

Injecting drug use in Brighton, Liverpool, and London: best estimates of prevalence and coverage of public health indicators

Study objective: To estimate the prevalence of injecting drug use (IDU) in three cities in England and to measure the coverage of key public health indicators. Design: Capture-recapture techniques with covariate effects. Setting: Liverpool, Brighton, and 12 London boroughs, 2000/01. Participants: IDU collated and matched across five data sources—community recruited survey, specialist drug treatment, arrest referral, syringe exchange, and accident and emergency—896 in Brighton, 1224 in Liverpool, and 6111 in London. Main results: It is estimated that in 2000/01 the number and prevalence of IDU aged 15–44 was 2300 (95%CI 1500 to 3700) and 2.0% (95%CI% 1.3% to 3.2%) in Brighton; 2900 (95%CI 2500 to 5000) and 1.5% (95%CI 1.3% to 2.6%) in Liverpool; 16 700 (95%CI 13 800 to 21 600) and 1.2% (95%CI 1.0% to 1.6%) in 12 London boroughs; with a prevalence of 1.7% (95%CI 1.2% to 3.3%) in inner London. It is estimated that: less than one in four IDU are in treatment in the three areas; syringe exchange programmes covered about 25% of injections in Brighton and Liverpool and 20% in London; and that the annual opioid mortality rate among IDU was 2% in Brighton compared with less than 1% in Liverpool and London. Conclusions: Credible estimates of the prevalence of injecting drug use (and key public health indicators) can be determined using covariate capture-recapture techniques. These suggest that: targets to double the number in treatment are possible: syringe distribution should be increased; and further attention, especially in Brighton, given to reducing overdose mortality.

Hepatitis C virus (HCV) prevalence, and injecting risk behaviour in multiple sites in England in 2004

Summary.  We sought to corroborate geographical differences in hepatitis C virus (HCV) prevalence and assess whether these can be explained by differences in injecting risk behaviour. A community recruited interview survey of 1058 injecting drug users (IDU) – including a blood spot specimen for antibody testing – was undertaken in seven cities in England. HCV prevalence varied from 27% to 74% across sites (χ2(6) = 115.3, P < 0.001). There was a significant variation in crack‐injection, prison history, injecting frequency, homelessness, groin injecting, syringe reuse and sharing between the sites. Adjustment for clustering by site and other covariates attenuated the odds ratios (OR) for most variables: e.g. crack injection changed from an unadjusted OR of >2 to an adjusted OR of 1.4 (95% CI 0.9–2.0). Remaining significant covariates included: homelessness (OR 2.2; 1.4–3.6); ever imprisonment (OR 1.7; 1.2–2.5); syringe sharing >18 months ago (OR 2.0; 1.3–3.0); injecting duration and age. Introducing site as a second level variable did not reach significance (P = 0.10). HCV prevalence among IDU reporting ‘never sharing’ was 48%. Geographical variation in HCV prevalence remains poorly explained, but should be the key focus of our surveillance effort. Measures of sharing and their interpretation require greater scrutiny.

Measuring the incidence, prevalence and genetic relatedness of hepatitis C infections among a community recruited sample of injecting drug users, using dried blood spots.

Summary.  Monitoring hepatitis C virus (HCV) infection among injecting drug users (IDUs) in the community is complicated by difficulties in obtaining biological specimens and biases in recruitment and follow‐up. This study examined the utility of dried blood spot (DBS) specimens from IDUs recruited using respondent‐driven sampling (RDS). Active IDUs underwent a computer‐assisted interview and provided a DBS sample, tested for HCV antibody (anti‐HCV) and HCV‐RNA. HCV incidence was estimated from the proportion of anti‐HCV‐negative subjects found HCV‐RNA‐positive and estimates of the duration of this state. Results were adjusted according to RDS derived sample weights. HCV‐RNA testing was performed on 288 DBS samples; 173 were anti‐HCV‐positive (54% weighted), of which 70 (42%, 95%CI 34–50% weighted) were RNA‐negative indicating cleared infection. Among the 115 anti‐HCV‐negatives, 14 were RNA‐positive suggesting an incidence of 38–47 per 100pyrs. Incident infections were younger than anti‐HCV‐negative and prevalent infections: 25 vs. 29 and 34, respectively. Incidence was highest among individuals with poor needle exchange coverage. One hundred and fourteen were genotyped (60 1a, 46 3a): a cluster of 14 had homology of >98.5% including 10 incident infections. Public health surveillance of HCV among IDUs could be enhanced through the collection of DBS samples with appropriate recruitment approaches. DBS allow differentiation between individuals with cleared infections, ongoing infection and those recently infected. They also enable virus characterization at genotype and nucleotide level. This would allow surveillance to inform development of harm reduction interventions, and the international evidence base for these.

Modelling the force of infection for hepatitis B and hepatitis C in injecting drug users in England and Wales

BackgroundInjecting drug use is a key risk factor, for several infections of public health importance, especially hepatitis B (HBV) and hepatitis C (HCV). In England and Wales, where less than 1% of the population are likely to be injecting drug users (IDUs), approximately 38% of laboratory reports of HBV, and 95% of HCV reports are attributed to injecting drug use.MethodsVoluntary unlinked anonymous surveys have been performed on IDUs in contact with specialist agencies throughout England and Wales. Since 1990 more than 20,000 saliva samples from current IDUs have been tested for markers of infection for HBV, HCV testing has been included since 1998. The analysis here considers those IDUs tested for HBV and HCV (n = 5,682) from 1998–2003. This study derives maximum likelihood estimates of the force of infection (the rate at which susceptible IDUs acquire infection) for HBV and HCV in the IDU population and their trends over time and injecting career length. The presence of individual heterogeneity of risk behaviour and background HBV prevalence due to routes of transmission other than injecting are also considered.ResultsFor both HBV and HCV, IDUs are at greatest risk from infection in their first year of injecting (Forces of infection in new initiates 1999–2003: HBV = 0.1076 95% C.I: 0.0840–0.1327 HCV = 0.1608 95% C.I: 0.1314–0.1942) compared to experienced IDUs (Force of infection in experienced IDUs 1999–2003: HBV = 0.0353 95% C.I: 0.0198–0.0596, HCV = 0.0526 95% C.I: 0.0310–0.0863) although independently of this there is evidence of heterogeneity of risk behaviour with a small number of IDUs at increased risk of infection. No trends in the FOI over time were detected. There was only limited evidence of background HBV infection due to factors other than injecting.ConclusionThe models highlight the need to increase interventions that target new initiates to injecting to reduce the transmission of blood-borne viruses. Although from the evidence here, identification of those individuals that engage in heightened at-risk behaviour may also help in planning effective interventions. The data and methods described here may provide a baseline for monitoring the success of public health interventions.

HIV among people who inject drugs in Central and Eastern Europe and Central Asia: a systematic review with implications for policy

Background and objectives HIV among people who inject drugs (PWID) is a major public health concern in Eastern and Central Europe and Central Asia. HIV transmission in this group is growing and over 27 000 HIV cases were diagnosed among PWID in 2010 alone. The objective of this systematic review was to examine risk factors associated with HIV prevalence among PWID in Central and Eastern Europe and Central Asia and to describe the response to HIV in this population and the policy environments in which they live. Design A systematic review of peer-reviewed and grey literature addressing HIV prevalence and risk factors for HIV prevalence among PWID and a synthesis of key resources describing the response to HIV in this population. We used a comprehensive search strategy across multiple electronic databases to collect original research papers addressing HIV prevalence and risk factors among PWID since 2005. We summarised the extent of key harm reduction interventions, and using a simple index of ‘enabling’ environment described the policy environments in which they are implemented. Studies reviewed Of the 5644 research papers identified from electronic databases and 40 documents collected from our grey literature search, 70 documents provided unique estimates of HIV and 14 provided multivariate risk factors for HIV among PWID. Results HIV prevalence varies widely, with generally low or medium (<5%) prevalence in Central Europe and high (>10%) prevalence in Eastern Europe. We found evidence for a number of structural factors associated with HIV including gender, socio-economic position and contact with law enforcement agencies. Conclusions The HIV epidemic among PWID in the region is varied, with the greatest burden generally in Eastern Europe. Data suggest that the current response to HIV among PWID is insufficient, and hindered by multiple environmental barriers including restricted access to services and unsupportive policy or social environments.

Frequency, factors and costs associated with injection site infections: Findings from a national multi-site survey of injecting drug users in England

BackgroundInjection site infections among injecting drug users (IDUs) have been associated with serious morbidity and health service costs in North America. This study explores the frequency, factors and costs associated with injection site infections among IDUs in England.MethodsUnlinked-anonymous survey during 2003/05 recruiting IDUs from community settings at seven locations across England. Self-reported injecting practice, symptoms of injection site infections (abscess or open wound) and health service utilisation data were collected using a questionnaire, participants also provided dried blood spot samples (tested for markers blood borne virus infections). Cost estimates were obtained by combining questionnaire data with information from national databases and the scientific literature.Results36% of the 1,058 participants reported an injection site infection in the last year. Those reporting an injection site infection were more likely to be female and aged over 24, and to have: injected into legs, groin, and hands in last year; injected on 14 or more days during the last four weeks; cleaned needles/syringes for reuse; injected crack-cocaine; antibodies to hepatitis C; and previously received prescribed substitute drug. Two-thirds of those with an injection site infection reported seeking medical advice; half attended an emergency department and three-quarters of these reported hospital admission. Simple conservative estimates of associated healthcare costs range from £15.5 million per year to as high as £30 million; though if less conservative unit costs assumptions are made the total may be much higher (£47 million). The vast majority of these costs are due to hospital admissions and the uncertainty is due to little data on length of hospital stays.ConclusionSymptoms of injection site infections are common among IDUs in England. The potential costs to the health service are substantial, but these costs need more accurate determination. Better-targeted interventions to support safer injection need to be developed and evaluated. The validity of self-reported symptoms, and the relationship between symptoms, infection severity, and health seeking behaviour require further research.

HCV treatment rates and sustained viral response among people who inject drugs in seven UK sites: real world results and modelling of treatment impact.

Hepatitis C virus (HCV) antiviral treatment for people who inject drugs (PWID) could prevent onwards transmission and reduce chronic prevalence. We assessed current PWID treatment rates in seven UK settings and projected the potential impact of current and scaled‐up treatment on HCV chronic prevalence. Data on number of PWID treated and sustained viral response rates (SVR) were collected from seven UK settings: Bristol (37–48% HCV chronic prevalence among PWID), East London (37–48%), Manchester (48–56%), Nottingham (37–44%), Plymouth (30–37%), Dundee (20–27%) and North Wales (27–33%). A model of HCV transmission among PWID projected the 10‐year impact of (i) current treatment rates and SVR (ii) scale‐up with interferon‐free direct acting antivirals (IFN‐free DAAs) with 90% SVR. Treatment rates varied from <5 to over 25 per 1000 PWID. Pooled intention‐to‐treat SVR for PWID were 45% genotypes 1/4 [95%CI 33–57%] and 61% genotypes 2/3 [95%CI 47–76%]. Projections of chronic HCV prevalence among PWID after 10 years of current levels of treatment overlapped substantially with current HCV prevalence estimates. Scaling‐up treatment to 26/1000 PWID annually (achieved already in two sites) with IFN‐free DAAs could achieve an observable absolute reduction in HCV chronic prevalence of at least 15% among PWID in all sites and greater than a halving in chronic HCV in Plymouth, Dundee and North Wales within a decade. Current treatment rates among PWID are unlikely to achieve observable reductions in HCV chronic prevalence over the next 10 years. Achievable scale‐up, however, could lead to substantial reductions in HCV chronic prevalence.