Impact of the COVID-19 Pandemic on HIV Test Uptake Among People Who Inject Drugs in the Context of an HIV Outbreak.

Glasgow, Scotland's largest city, has been experiencing an HIV outbreak among people who inject drugs (PWID) since 2015. A key focus of the public health response has been to increase HIV testing among those at risk of infection. Our aim was to assess the impact of COVID-19 on HIV testing among PWID in Glasgow. HIV test uptake in the last 12 months was quantified among: (1) PWID recruited in six Needle Exchange Surveillance Initiative (NESI) surveys (n = 6110); linked laboratory data for (2) people prescribed opioid agonist therapy (OAT) (n = 14,527) and (3) people hospitalised for an injecting-related hospital admission (IRHA) (n = 12,621) across four time periods: pre-outbreak (2010-2014); early-outbreak (2015-2016); ongoing-outbreak (2017-2019); and COVID-19 (2020-June 21). From the pre to ongoing period, HIV testing increased: the highest among people recruited in NESI (from 28% to 56%) and on OAT (from 17% to 54%) while the lowest was among people with an IRHA (from 15% to 42%). From the ongoing to the COVID-19 period, HIV testing decreased markedly among people prescribed OAT, from 54% to 37% (aOR 0.50, 95% CI 0.48-0.53), but increased marginally among people with an IRHA from 42% to 47% (aOR 1.19, 95% CI 1.08-1.31). In conclusion, progress in increasing testing in response to the HIV outbreak has been eroded by COVID-19. Adoption of a linked data approach could be warranted in other settings to inform efforts to eliminate HIV transmission.

Incidence of HIV and hepatitis C virus among people who inject drugs, and associations with age and sex or gender: a global systematic review and meta-analysis.

BACKGROUND: Measuring the incidence of HIV and hepatitis C virus (HCV) infection among people who inject drugs (PWID) is key to track progress towards elimination. We aimed to summarise global data on HIV and primary HCV incidence among PWID and associations with age and sex or gender. METHODS: In this systematic review and meta-analysis, we updated an existing database of HIV and HCV incidence studies among PWID by searching MEDLINE, Embase, and PsycINFO, capturing studies published between Jan 1, 2000, and Dec 12, 2022, with no language or study design restrictions. We contacted authors of identified studies for unpublished or updated data. We included studies that estimated incidence by longitudinally re-testing people at risk of infection or by using assays for recent infection. We pooled incidence and relative risk (RR; young [generally defined as ≤25 years] vs older PWID; women vs men) estimates using random-effects meta-analysis and assessed risk of bias with a modified Newcastle-Ottawa scale. This study is registered with PROSPERO, CRD42020220884. FINDINGS: Our updated search identified 9493 publications, of which 211 were eligible for full-text review. An additional 377 full-text records from our existing database and five records identified through cross-referencing were assessed. Including 28 unpublished records, 125 records met the inclusion criteria. We identified 64 estimates of HIV incidence (30 from high-income countries [HICs] and 34 from low-income or middle-income countries [LMICs]) and 66 estimates of HCV incidence (52 from HICs and 14 from LMICs). 41 (64%) of 64 HIV and 42 (64%) of 66 HCV estimates were from single cities rather than being multi-city or nationwide. Estimates were measured over 1987-2021 for HIV and 1992-2021 for HCV. Pooled HIV incidence was 1·7 per 100 person-years (95% CI 1·3-2·3; I2=98·4%) and pooled HCV incidence was 12·1 per 100 person-years (10·0-14·6; I2=97·2%). Young PWID had a greater risk of HIV (RR 1·5, 95% CI 1·2-1·8; I2=66·9%) and HCV (1·5, 1·3-1·8; I2=70·6%) acquisition than older PWID. Women had a greater risk of HIV (RR 1·4, 95% CI 1·1-1·6; I2=55·3%) and HCV (1·2, 1·1-1·3; I2=43·3%) acquisition than men. For both HIV and HCV, the median risk-of-bias score was 6 (IQR 6-7), indicating moderate risk. INTERPRETATION: Although sparse, available HIV and HCV incidence estimates offer insights into global levels of HIV and HCV transmission among PWID. Intensified efforts are needed to keep track of the HIV and HCV epidemics among PWID and to expand access to age-appropriate and gender-appropriate prevention services that serve young PWID and women who inject drugs. FUNDING: Canadian Institutes of Health Research, Fonds de recherche du Québec-Santé, Canadian Network on Hepatitis C, UK National Institute for Health and Care Research, and WHO.

Improved health-related quality of life after hepatitis C viraemic clearance among people who inject drugs may not be durable.

BACKGROUND AND AIMS: Chronic infection with the hepatitis C virus (HCV) has a detrimental impact on health-related quality of life (QoL). Scale-up of HCV direct-acting antiviral (DAA) therapy among people who inject drugs (PWID) is underway in several countries since the introduction of interferon-free regimens. This study aimed to assess the impact of DAA treatment success on QoL for PWID. DESIGN: Cross-sectional study using two rounds of the Needle Exchange Surveillance Initiative, a national anonymous bio-behavioural survey and a longitudinal study involving PWID who underwent DAA therapy. SETTING: The setting for the cross-sectional study was Scotland (2017-2018, 2019-2020). The setting for the longitudinal study was the Tayside region of Scotland (2019-2021). PARTICIPANTS: In the cross-sectional study PWID were recruited from services providing injecting equipment (n = 4009). In the longitudinal study, participants were PWID on DAA therapy (n = 83). MEASUREMENTS: In the cross-sectional study, the association between QoL (measured using the EQ-5D-5L quality of life instrument) and HCV diagnosis and treatment was assessed using multilevel linear regression. In the longitudinal study, QoL was compared at four timepoints using multilevel regression, from treatment commencement until 12 months following commencement. FINDINGS: In the cross-sectional study, 41% (n = 1618) were ever chronically HCV infected, of whom 78% (n = 1262) were aware of their status and of whom 64% (n = 704) had undergone DAA therapy. There was no evidence for a marked QoL improvement associated with viral clearance among those treated for HCV (B = 0.03; 95% CI, -0.03 to 0.09). In the longitudinal study, improved QoL was observed at the sustained virologic response test timepoint (B = 0.18; 95% CI, 0.10-0.27), but this was not maintained at 12 months following start of treatment (B = 0.02; 95% CI, -0.05 to 0.10). CONCLUSIONS: Successful direct-acting antiviral therapy for hepatitis C infection may not lead to a durable improvement in quality of life among people who inject drugs, although there may be a transient improvement around the time of sustained virologic response. Economic models of the impact of scaling-up treatment may need to include more conservative quality of life benefits over and above reductions in mortality, disease progression and transmission of infection.

Examining the impact of the first wave of COVID-19 and associated control measures on interventions to prevent blood-borne viruses among people who inject drugs in Scotland: an interrupted time series study.

BACKGROUND: COVID-19 has likely affected the delivery of interventions to prevent blood-borne viruses (BBVs) among people who inject drugs (PWID). We examined the impact of the first wave of COVID-19 in Scotland on: 1) needle and syringe provision (NSP), 2) opioid agonist therapy (OAT) and 3) BBV testing. METHODS: An interrupted time series study design; 23rd March 2020 (date of the first 'lockdown') was chosen as the key date. RESULTS: The number of HIV tests and HCV tests in drug services/prisons, and the number of needles/syringes (N/S) distributed decreased by 94% (RR=0.062, 95% CI 0.041-0.094, p < 0.001), 95% (RR=0.049, 95% CI 0.034-0.069, p < 0.001) and 18% (RR = 0.816, 95% CI 0.750-0.887, p < 0.001), respectively, immediately after lockdown. Post-lockdown, an increasing trend was observed relating to the number of N/S distributed (0.6%; RR = 1.006, 95% CI 1.001-1.012, p = 0.015), HIV tests (12.1%; RR = 1.121, 95% CI 1.092-1.152, p < 0.001) and HCV tests (13.2%; RR = 1.132, 95 CI 1.106-1.158, p < 0.001). Trends relating to the total amount of methadone prescribed remained stable, but a decreasing trend in the number of prescriptions (2.4%; RR = 0.976, 95% CI 0.959-0.993, p = 0.006) and an increasing trend in the quantity prescribed per prescription (2.8%; RR = 1.028, 95% CI 1.013-1.042, p < 0.001) was observed post-lockdown. CONCLUSIONS: COVID-19 impacted the delivery of BBV prevention services for PWID in Scotland. While there is evidence of service recovery; further effort is likely required to return some intervention coverage to pre-pandemic levels in the context of subsequent waves of COVID-19.

Population-level estimates of hepatitis C reinfection post scale-up of direct-acting antivirals among people who inject drugs.

BACKGROUND & AIMS: Scale-up of highly effective direct-acting antivirals (DAAs) for HCV among people who inject drugs (PWID) in Scotland has led to a reduction in the prevalence of viraemia in this population. However, the extent of reinfection among those treated with DAAs remains uncertain. We estimated HCV reinfection rates among PWID in Scotland by treatment setting, pre- and post-introduction of DAAs, and the potential number of undiagnosed reinfections resulting from incomplete follow-up testing. METHODS: Through linkage of national clinical and laboratory HCV data, a retrospective cohort of PWID who commenced treatment between 2000-2018 and achieved a sustained virological response (SVR) were followed up for reinfection to December 2019. Reinfection was defined as a positive HCV antigen or RNA test. RESULTS: Of 5,686 SVRs among 5,592 PWID, 4,126 (73%) had an HCV RNA or antigen test post-SVR. Of those retested, we identified 361 reinfections (3.9/100 person-years [PY]). The reinfection rate increased from 1.5/100 PY among PWID treated in 2000-2009 to 8.8/100 PY in 2017-2018. The highest reinfection rates were observed among those treated in prison (14.3/100 PY) and community settings (9.5/100 PY). Among those treated in the DAA era (2015-2018), 68% were tested within the first year post-SVR but only 30% in the second year; while 169 reinfections were diagnosed in follow-up, an estimated 200 reinfections (54% of the estimated total) had gone undetected. CONCLUSIONS: HCV reinfection rates among PWID in Scotland have risen alongside the scale-up of DAAs and broadened access to treatment for those at highest risk, through delivery in community drug services. Promotion of HCV testing post-SVR among PWID is essential to ensure those reinfected are identified and retreated promptly. LAY SUMMARY: Increased rates of hepatitis C reinfection in Scotland were observed following the rapid scale-up of highly effective direct-acting antiviral (DAA) treatments among people who inject drugs. This demonstrates that community-based treatment pathways are reaching high-risk groups, regarded vital in efforts to eliminate the virus. However, we estimate that less than half of reinfections have been detected in the DAA era because of inadequate levels of retesting beyond the first year following successful treatment. Sustained efforts that involve high coverage of harm reduction measures and high uptake of annual testing are required to ensure prompt diagnosis and treatment of those reinfected if the goals of elimination are to be met.

Evaluation of the scale-up of HIV testing among people who inject drugs in Scotland in the context of an ongoing HIV outbreak.

BACKGROUND: A large outbreak of HIV among people who inject drugs (PWID) has been ongoing in Glasgow city centre (GCC), Scotland since early 2015. The outbreak is associated with high levels of homelessness, cocaine injecting and injecting in public places. A key component of the public health response was the scale-up of HIV testing in a range of services engaged with PWID. Our aims were to: 1) evaluate the extent of and change in HIV testing over the course of the outbreak and 2) examine factors associated with reporting an HIV test. METHODS: Self-report of an HIV test in the last 12 months was collected for 15,081 PWID interviewed in six national cross-sectional bio-behavioural surveys during 2008-2018. Multi-variate logistic regression was undertaken to determine trends in HIV testing by region of recruitment (GCC; rest of Glasgow; other Scottish city centres (SCC); and rest of Scotland) and outbreak period (pre: 2008-14; early: 2015-16; ongoing: 2017-18). RESULTS: HIV testing increased across all regions and was most pronounced in GCC comparing the ongoing (67%) to the pre-outbreak period (33%) (aOR=4.68, 95% CI 3.23 to 6.77, p<0.001). However, compared to other SCCs pre-outbreak (with 46% reporting testing), those recruited in GCC had a lower odds of HIV testing early outbreak (aOR=0.37, 95% CI 0.27 to 0.54, p<0.001) and more modest increased odds in the ongoing outbreak period (aOR=1.41, 95% CI 0.97 to 2.05, p=0.069). Among PWID recruited in the whole of Glasgow in the ongoing phase, reporting an HIV test was associated with injecting cocaine or in public places (aOR=2.20, 95% CI 1.53 to 3.17, p<0.001), receipt of methadone (aOR=1.48, 95% CI 1.01 to 2.17, p=0.042) and incarceration in the last year (aOR=1.72, 95% CI 1.18 to 2.51, p=0.004). CONCLUSIONS: Relatively low levels of HIV testing pre- and early-outbreak likely hindered efforts to control the spread of infection among PWID in Glasgow. Uptake has since increased with expansion of testing across multiple settings, particularly among those at high risk of infection. Further effort is needed to ensure the vast majority of PWID are regularly tested, not just in the epicentre of the outbreak but in other areas with low population prevalence of infection.

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). DESIGN, SETTING AND PARTICIPANTS: Natural experiment, evaluated using data from national biennial surveys of PWID and national clinical data. Services providing injecting equipment (2010-18) and HCV treatment clinics (2017-18) across Scotland. A total of 12 492 PWID who completed a questionnaire and provided a blood spot (tested for HCV-antibodies and RNA); 4105 individuals who initiated HCV treatment. INTERVENTION AND COMPARATOR, MEASUREMENTS: The intervention was rapid DAA scale-up among PWID, which occurred in Tayside. The comparator was GGC/RoS. Trends in HCV viraemia and uptake of HCV therapy over time; sustained viral response (SVR) rates to therapy by region and treatment setting. 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.

High willingness to use drug consumption rooms among people who inject drugs in Scotland: findings from a national bio-behavioural survey among people who inject drugs.

BACKGROUND: To address rising drug-related harms (including significant transmission of HIV) among people who inject drugs (PWID) in Glasgow, officials have proposed the introduction of the UK's first drug consumption room (DCR) in Glasgow city centre. Using a nationally representative sample, this study aimed to determine willingness to use a DCR among PWID nationally, in Glasgow city centre (the proposed DCR location), other Scottish city centres (excluding Glasgow) and the rest of Scotland (excluding city centres). METHODS: Bio-behavioural survey, of 1469 current PWID (injected in last 6 months) across Scotland during 2017-18. Willingness to use DCRs was examined by drug-related risk behaviours and harms overall in Scotland, and then stratified by Glasgow city centre (n = 219), other Scottish city centres (n = 226) and the rest of Scotland (n = 1024). RESULTS: The majority of PWID overall in Scotland (75%) were willing to use a DCR; willingness was higher among those recruited in Glasgow city centre (83%) and other Scottish city centres (83%), compared to the rest of Scotland (72%) (p < 0.001). Willingness was greater among PWID who reported (compared to those who did not report) injecting heroin (76%, p = 0.002), cocaine injecting (79%, p = 0.014), homelessness (86%, p < 0.001), public injecting (87%, p < 0.001) and an overdose (80%, p = 0.026). Willingness was found to be associated with a cumulative multiple risk variable: increased from 66% among those with a score of zero to 85% with a score of at least three (p < 0.001). CONCLUSIONS: The vast majority of PWID at greatest risk of drug-related harm in Glasgow and elsewhere in Scotland would be willing to use a DCR, supporting proposals for the introduction of DCRs nationally.

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.

Evaluating the population impact of hepatitis C direct acting antiviral treatment as prevention for people who inject drugs (EPIToPe) - a natural experiment (protocol).

INTRODUCTION: Hepatitis C virus (HCV) is the second largest contributor to liver disease in the UK, with injecting drug use as the main risk factor among the estimated 200 000 people currently infected. Despite effective prevention interventions, chronic HCV prevalence remains around 40% among people who inject drugs (PWID). New direct-acting antiviral (DAA) HCV therapies combine high cure rates (>90%) and short treatment duration (8 to 12 weeks). Theoretical mathematical modelling evidence suggests HCV treatment scale-up can prevent transmission and substantially reduce HCV prevalence/incidence among PWID. Our primary aim is to generate empirical evidence on the effectiveness of HCV 'Treatment as Prevention' (TasP) in PWID. METHODS AND ANALYSIS: We plan to establish a natural experiment with Tayside, Scotland, as a single intervention site where HCV care pathways are being expanded (including specialist drug treatment clinics, needle and syringe programmes (NSPs), pharmacies and prison) and HCV treatment for PWID is being rapidly scaled-up. Other sites in Scotland and England will act as potential controls. Over 2 years from 2017/2018, at least 500 PWID will be treated in Tayside, which simulation studies project will reduce chronic HCV prevalence among PWID by 62% (from 26% to 10%) and HCV incidence will fall by approximately 2/3 (from 4.2 per 100 person-years (p100py) to 1.4 p100py). Treatment response and re-infection rates will be monitored. We will conduct focus groups and interviews with service providers and patients that accept and decline treatment to identify barriers and facilitators in implementing TasP. We will conduct longitudinal interviews with up to 40 PWID to assess whether successful HCV treatment alters their perspectives on and engagement with drug treatment and recovery. Trained peer researchers will be involved in data collection and dissemination. The primary outcome - chronic HCV prevalence in PWID - is measured using information from the Needle Exchange Surveillance Initiative survey in Scotland and the Unlinked Anonymous Monitoring Programme in England, conducted at least four times before and three times during and after the intervention. We will adapt Bayesian synthetic control methods (specifically the Causal Impact Method) to generate the cumulative impact of the intervention on chronic HCV prevalence and incidence. We will use a dynamic HCV transmission and economic model to evaluate the cost-effectiveness of the HCV TasP intervention, and to estimate the contribution of the scale-up in HCV treatment to observe changes in HCV prevalence. Through the qualitative data we will systematically explore key mechanisms of TasP real world implementation from provider and patient perspectives to develop a manual for scaling up HCV treatment in other settings. We will compare qualitative accounts of drug treatment and recovery with a 'virtual cohort' of PWID linking information on HCV treatment with Scottish Drug treatment databases to test whether DAA treatment improves drug treatment outcomes. ETHICS AND DISSEMINATION: Extending HCV community care pathways is covered by ethics (ERADICATE C, ISRCTN27564683, Super DOT C Trial clinicaltrials.gov: NCT02706223). Ethical approval for extra data collection from patients including health utilities and qualitative interviews has been granted (REC ref: 18/ES/0128) and ISCRCTN registration has been completed (ISRCTN72038467). Our findings will have direct National Health Service and patient relevance; informing prioritisation given to early HCV treatment for PWID. We will present findings to practitioners and policymakers, and support design of an evaluation of HCV TasP in England.

Re-emergence of HIV related to injecting drug use despite a comprehensive harm reduction environment: a cross-sectional analysis.

BACKGROUND: In 2015, an outbreak of HIV was identified among people who inject drugs (PWID) in the Greater Glasgow and Clyde (GGC) area of Scotland, an area which distributes more than 1 million needles and syringes per year. This is the largest such incident in the UK for 30 years. Here, we provide an epidemiological analysis of the impact of the outbreak on HIV prevalence trends in the population and the individual and environmental risk factors associated with infection. METHODS: Four cross-sectional, anonymous, bio-behavioural surveys of almost 4000 PWID attending services providing injecting equipment across GGC between 2011 and 2018 were analysed. Participants were recruited by trained independent interviewers and eligible if they had a history of injecting drug use, either current (within the past 6 months) or historical. Interviewers asked participants questions about demographics, behaviours, and service use and to give a dried blood spot sample that was tested anonymously for the presence of blood-borne viruses. Our primary outcome measure was HIV infection status, as determined by the dried blood spot sample. We removed duplicates and participants with missing data and used all remaining participants to examine trends in prevalence of HIV infection, risk behaviours, and intervention coverage. We then did multivariate analysis with adjusted and unadjusted logistic regression to determine individual and environmental factors associated with HIV infection. FINDINGS: The overall GGC sample comprised 3641 PWID; data from 2712 PWID were available for multivariate analysis after further removal of duplicate participants and missing data. Between 2011 and 2018, HIV prevalence in GGC rose from 0·1% (95% CI 0·0-0·6) to 4·8% (3·4-6·2) overall, and from 1·1% (0·2-6·2) to 10·8% (7·4-15·5) in Glasgow city centre. Over the same period, the prevalence of cocaine injecting in all individuals in GGC in our sample rose from 16% (129/805) to 50% (291/583) overall, and from 37% (26/70) to 77% (117/153) in Glasgow city centre. HIV infection was more likely among PWID who had participated in surveys after the start of the outbreak in 2014 (adjusted odds ratio 3·4, 95% CI 1·7-6·7; p=0·00052), been homeless in the past 6 months (3·0, 1·7-5·0; p<0·0001), had had more than five incarcerations since they first began injecting (2·1, 1·2-3·7; p=0·0098); and had injected cocaine within the past 6 months (6·7, 3·8-12·1; p<0·0001). Age (per 1-year increase) was also a significant factor (1·1, 1·0-1·1; p=0·0016) but sex was not (1·7, 0·9-3·2; p=0·083). INTERPRETATION: Despite high coverage of harm reduction interventions, Glasgow has experienced a rapid rise in prevalence of HIV among its PWID population, associated with homelessness, incarceration, and a major shift to injection of cocaine. Robust surveillance through regular HIV testing of high-risk populations is crucial to ensure outbreaks are detected and rapid responses are informed by the best available evidence. FUNDING: Health Protection Scotland.

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. FUNDING: Engineering and Physical Sciences Research Council, National Institute for Health Research, National Institutes of Health.

Association between universal hepatitis B prison vaccination, vaccine uptake and hepatitis B infection among people who inject drugs.

BACKGROUND AND AIMS: In Scotland, hepatitis B virus (HBV) vaccination for all prisoners was introduced in 1999; here, we examine the impact of this programme among people who inject drugs (PWID) in the community. This study aimed to compare rates of HBV vaccine uptake before and after implementation of the prison programme and to estimate the determinants of vaccine uptake, the levels of ever/current HBV infection and the associations between vaccine uptake and ever/current HBV infection. DESIGN: Data collected via serial cross-sectional surveys were used to compare the proportion who reported being vaccinated over time. For the 2013-14 survey, rates of ever/current HBV infection were calculated and the associations between vaccine uptake and ever/current HBV infection were examined using logistic regression. SETTING: Services providing injecting equipment and drug treatment and street sites in Glasgow (1993-2002) and throughout Scotland (2008-14). PARTICIPANTS: More than 10 000 PWID in total were recruited in the surveys. MEASUREMENTS: Participants completed a questionnaire (all years) to ascertain self-reported vaccine uptake and provided a blood spot (in 2013-14), tested for HBV core antibodies (anti-HBc) and surface antigen (HBsAg). FINDINGS: Among recent-onset PWID in Glasgow, vaccine uptake increased from 16% in 1993 to 59% in 2008-14 (P < 0.001). Among all PWID in Scotland, uptake increased further from 71% in 2008-09 to 77% in 2013-14 (P < 0.001) and was associated with incarceration [adjusted odds ratio (aOR) = 2.91, 95% confidence interval (CI) = 2.23-3.79]. The prevalence of anti-HBc and HBsAg in Scotland was 2.6 and 0.3%, respectively, among PWID who had commenced injecting in the decade since the programme's introduction. Vaccination was associated with reduced odds of ever (aOR = 0.60, CI = 0.37-0.97) and current (aOR = 0.40, CI = 0.16-0.97) HBV infection. CONCLUSIONS: In Scotland, uptake of hepatitis B virus (HBV) vaccination among people who inject drugs (PWID) in the community has increased since the 1999 introduction of universal prison vaccination, and current levels of HBV infection among PWID are low compared with other European countries.

HCV avidity as a tool for detection of recent HCV infection: Sensitivity depends on HCV genotype.

Accurate detection of incident hepatitis C virus (HCV) infection is required to target and evaluate public health interventions, but acute infection is largely asymptomatic and difficult to detect using traditional methods. Our aim was to evaluate a previously developed HCV avidity assay to distinguish acute from chronic HCV infection. Plasma samples collected from recent seroconversion subjects in two large Australian cohorts were tested using the avidity assay, and the avidity index (AI) was calculated. Demographic and clinical characteristics of patients with low/high AI were compared via logistic regression. Sensitivity and specificity of the assay for recent infection and the mean duration of recent infection (MDRI) were estimated stratified by HCV genotype. Avidity was assessed in 567 samples (from 215 participants), including 304 with viraemia (defined as ≥250 IU/mL). An inverse relationship between AI and infection duration was found in viraemic samples only. The adjusted odds of a low AI (<30%) decreased with infection duration (odds ratio [OR] per week of 0.93; 95% CI:0.89-0.97), and were lower for G1 compared with G3 samples (OR = 0.14; 95% CI:0.05-0.39). Defining recent infection as <26 weeks, sensitivity (at AI cut-off of 20%) was estimated at 48% (95% CI:39-56%), 36% (95% CI:20-52%), and 65% (95% CI:54-75%) and MDRI was 116, 83, and 152 days for all genotypes, G1, and G3, respectively. Specificity (≥52 weeks infection duration, all genotypes) was 96% (95% CI:90-98%). HCV avidity testing has utility for detecting recent HCV infection in patients, and for assessing progress in reaching incidence targets for eliminating transmission, but variation in assay performance across genotype should be recognized.

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.

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.

Review and meta-analysis of the association between self-reported sharing of needles/syringes and hepatitis C virus prevalence and incidence among people who inject drugs in Europe.

BACKGROUND: Although sharing needles/syringes (N/S) is a recognised risk factor for the hepatitis C virus (HCV), epidemiological studies have shown inconsistent associations between self-reported N/S sharing and biological markers of HCV infection. This review aims to summarise, and explore factors that may explain the variation in, the measure of association between self-reported sharing of N/S and HCV prevalence/incidence among people who inject drugs (PWID). METHODS: Studies undertaken in Europe during 1990-2011 were identified through an electronic literature search. Eligible studies reported HCV prevalence (or incidence) among those who reported ever/never (or recent/non-recent) sharing of N/S. Meta-analysis was undertaken to generate a pooled estimate of the association and heterogeneity was explored using stratified analyses. RESULTS: Sixteen cross-sectional studies and four longitudinal studies were included. Pooled prevalence and incidence of HCV was 59% and 11% among PWID who reported never and not recently sharing N/S, respectively. Random effects meta-analysis generated a pooled odds ratio (OR) of 3.3 (95% CI 2.4-4.6), comparing HCV infection among those who ever (or recently) shared N/S relative to those who reported never (or not recently) sharing. There was substantial heterogeneity between the study effect sizes (I(2)=72.8%). 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. CONCLUSION: We found high incidence/prevalence rates among those who did not report sharing N/S during the risk period, which may be due to a combination of unmeasured risk factors and reporting bias. Study design and population are likely to be important modifiers of the size and strength of association between HCV and N/S sharing.

Decrease in health-related quality of life associated with awareness of hepatitis C virus infection among people who inject drugs in Scotland.

BACKGROUND & AIMS: Chronic hepatitis C virus (HCV) infection can significantly reduce health-related quality of life (QoL), but it is not clear if reduction is associated with the infection or with being aware of one's infection status. Understanding the impact of a HCV diagnosis on QoL is essential to inform decision-making regarding screening/testing and treatment. METHODS: Using a cross-sectional design, we assessed QoL in 2898 people who inject drugs (PWID), surveyed in Scotland during 2010 using EQ-5D. Multifactorial regression compared self-reported QoL between PWID who were (i) chronically HCV-infected and aware of their infected status, (ii) chronically HCV-infected but unaware, and (iii) not chronically infected. RESULTS: Median time since onset of injecting was 10years; not chronically infected PWID were younger and had shorter injecting careers than chronically infected PWID. Median EQ-5D was highest for the not chronically infected and the chronic/unaware groups (0.73) compared with the chronic/aware group (0.66). After adjustment for demographic and behavioural co-factors, QoL was significantly reduced in chronic/aware compared with chronic/unaware PWID (adjusted B=-0.09, p=0.005); there was no evidence for a difference in QoL between not chronically infected and chronic/unaware PWID (adjusted B=-0.03, p=0.13). CONCLUSIONS: Awareness of one's chronic HCV status was associated with reduced health-related QoL, but there was no evidence for further reduction attributable to chronic infection itself after adjusting for important covariate differences.

Infections with spore-forming bacteria in persons who inject drugs, 2000-2009.

Since 2000 in the United Kingdom, infections caused by spore-forming bacteria have been associated with increasing illness and death among persons who inject drugs (PWID). To assess temporal and geographic trends in these illnesses (botulism, tetanus, Clostridium novyi infection, and anthrax), we compared rates across England and Scotland for 2000-2009. Overall, 295 infections were reported: 1.45 per 1,000 PWID in England and 4.01 per 1,000 PWID in Scotland. The higher rate in Scotland was mainly attributable to C. novyi infection and anthrax; rates of botulism and tetanus were comparable in both countries. The temporal and geographic clustering of cases of C. novyi and anthrax into outbreaks suggests possible contamination of specific heroin batches; in contrast, the more sporadic nature of tetanus and botulism cases suggests that these spores might more commonly exist in the drug supply or local environment although at varying levels. PWID should be advised about treatment programs, injecting hygiene, risks, and vaccinations.