Association between antibody responses post-vaccination and severe COVID-19 outcomes in Scotland.

Several population-level studies have described individual clinical risk factors associated with suboptimal antibody responses following COVID-19 vaccination, but none have examined multimorbidity. Others have shown that suboptimal post-vaccination responses offer reduced protection to subsequent SARS-CoV-2 infection; however, the level of protection from COVID-19 hospitalisation/death remains unconfirmed. We use national Scottish datasets to investigate the association between multimorbidity and testing antibody-negative, examining the correlation between antibody levels and subsequent COVID-19 hospitalisation/death among double-vaccinated individuals. We found that individuals with multimorbidity ( ≥ five conditions) were more likely to test antibody-negative post-vaccination and 13.37 [6.05-29.53] times more likely to be hospitalised/die from COVID-19 than individuals without conditions. We also show a dose-dependent association between post-vaccination antibody levels and COVID-19 hospitalisation or death, with those with undetectable antibody levels at a significantly higher risk (HR 9.21 [95% CI 4.63-18.29]) of these serious outcomes compared to those with high antibody levels.

Evaluating the effect of direct-acting antiviral agent treatment scale-up on Hepatitis C virus prevalence among people who inject drugs in UK.

BACKGROUND: There is limited empirical work assessing the effectiveness of treatment as prevention (TasP) in reducing HCV prevalence among people who inject drugs (PWID). Here, we used survey data from the UK during 2010-2020, to evaluate the impact of direct-acting antiviral agent (DAA) treatment scale-up, which started in 2015, on HCV prevalence among PWID. METHODS: We fitted a logistic regression to time/location specific data on prevalence from the Needle Exchange Surveillance Initiative in Scotland and Unlinked Anonymous Monitoring programme in England. For each post-intervention year and location, we quantified the effect of TasP as the difference between estimated prevalence and its counterfactual (prevalence in the absence of scale-up). Progress to elimination was assessed by comparing most recent prevalence against one in 2015. RESULTS: In 2015, prevalence ranged from 0.44 to 0.71 across the 23 locations (3 Scottish, 20 English). Compared to counterfactuals, there was an absolute reduction of 46% (95% credible interval [32%,59%]) in Tayside in 2020, 35% ([24%,44%]) in Glasgow in 2019, and 25% ([10%,39%]) in the Rest of Scotland in 2020. The English sites with highest estimated absolute reductions in 2021 were South Yorkshire (45%, [29%,58%]), Thames Valley (49%, [34%,59%]) and West London (41%, [14%,59%]). Compared to 2015, there was 80% probability that prevalence had fallen by 65% in Tayside, 53% in Glasgow and 36% in the Rest of Scotland. The English sites with highest % prevalence decrease compared to 2015, achieved with probability 80%, were Chesire & Merseyside (70%), South Yorkshire (65%) and Thames Valley (71%). Higher treatment intensity was associated with higher reductions in prevalence. CONCLUSION: Conclusion. Real-world evidence showing substantial reductions in chronic HCV associated with increase of HCV treatment scale-up in the community thus supporting the effectiveness of HCV treatmen as prevention in people who inject drugs.

Factors associated with SARS-CoV-2 testing, diagnosis and COVID-19 disease among individuals prescribed opioid-agonist treatment: a nationwide retrospective cohort study.

OBJECTIVES: Among people receiving opioid-agonist treatment (OAT), the risk of COVID-19 infection and disease may be higher owing to underlying health problems and vulnerable social circumstances. We aimed to determine whether recent OAT, compared to past exposure, affected risk of (i) testing for SARS-CoV-2, (ii) testing positive for SARS-CoV-2 and (iii) being hospitalized/dying with COVID-19 disease. METHODS: We included individuals prescribed OAT in Scotland between 2015 and 2020. We performed record linkage to SARS-CoV-2 PCR testing, vaccination, hospitalization, and mortality data, and followed up from March-2020 to December-2021. We used proportional hazards analysis and multivariate logistic regression to estimate associations between recent OAT prescription (in the previous two months), compared to past exposure (off treatment for over a year), and COVID-19 outcomes. Models were adjusted for confounders. RESULTS: Among 36,093 individuals prescribed OAT, 19,071 (52.9%) were tested for SARS-CoV-2, 2,896 (8.3%) tested positive and 552 (1.5%) were hospitalized/died with COVID-19. Recent OAT, compared to past exposure, was associated with lower odds of testing positive among those tested (aOR, 0.63; 95% CI, 0.57, 0.69). However, among those testing positive, recent OAT was associated with two-fold higher odds of hospitalization/death (aOR, 2.04; 95% CI, 1.60, 2.59). CONCLUSION: We found that recent OAT was associated with lower odds of SARS-CoV-2 infection, but with higher odds of disease once diagnosed. Clinical studies are needed to unravel the role of OAT in these associations. Enhanced effort is warranted to increase vaccine coverage among OAT patients to mitigate severe consequences of COVID-19.

Risk of drug-related death associated with co-prescribing of gabapentinoids and Z-drugs among people receiving opioid-agonist treatment: A national retrospective cohort study.

BACKGROUND: Prescribing of gabapentinoids and Z-drug-hypnotics has increased in the population and among people receiving opioid-agonist treatment (OAT) for opioid dependence. Evidence is mixed on whether co-prescribing of sedatives such as gabapentinoids and Z-drugs during OAT increases risk of drug-related death (DRD). METHODS: We conducted a retrospective cohort study of individuals prescribed OAT between 2011 and 2020 in Scotland. Prescribing records were linked to mortality data and other healthcare datasets (sociodemographic, comorbidity). We identified episodes of treatment with gabapentinoids/Z-drugs and used multivariable quasi-Poisson regression to model associations between co-prescription and DRD risk. RESULTS: Among 46,602 individuals with 304,783 person-years of follow-up, we found that co-prescription was common, with 25 % and 34 % ever being co-prescribed gabapentinoids and Z-drugs, respectively. Gabapentinoid exposure was strongly associated (adjusted hazard ratio (aHR)=2·18, 95 % CI=1·92, 2·46) and Z-drug exposure moderately associated (aHR=1·39, 95 % CI=1·15, 1·66) with elevated risk of DRD. Gabapentinoid exposure was associated with DRD risk on and off OAT; Z-drug exposure was less strongly associated with DRD risk when on OAT. CONCLUSIONS: Co-prescription of gabapentinoids and Z-drugs is common among OAT patients. However, co-prescription is associated with increased risk of DRD. Alternatives to prescribing sedative medications to OAT patients and/or greater monitoring - if prescribed - are needed.

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.

SARS-CoV-2 vaccine uptake and risks of severe COVID-19 disease among people prescribed opioid agonist therapy in Scotland.

BACKGROUND: There is limited evidence quantifying the risk of severe COVID-19 disease among people with opioid dependence. We examined vaccine uptake and severe disease (admission to critical care or death with COVID-19) among individuals prescribed opioid agonist therapy (OAT). METHOD: A case-control design was used to examine vaccine uptake in those prescribed OAT compared with the general population, and the association between severe disease and OAT. In both analyses, 10 controls from the general population were matched (to each OAT recipient and COVID-19 case, respectively) according to socio-demographic factors. Conditional logistic regression was used to estimate rate ratios (RR) for severe disease. RESULTS: Vaccine uptake was markedly lower in the OAT cohort (dose 1: 67%, dose 2: 53% and dose 3: 31%) compared with matched controls (76%, 72% and 57%, respectively). Those prescribed OAT within the last 5 years, compared with those not prescribed, had increased risk of severe COVID-19 (RR 3.38, 95% CI 2.75 to 4.15), particularly in the fourth wave (RR 6.58, 95% CI 4.20 to 10.32); adjustment for comorbidity and vaccine status attenuated this risk (adjusted RR (aRR) 2.43, 95% CI 1.95 to 3.02; wave 4 aRR 3.78, 95% CI 2.30 to 6.20). Increased risk was also observed for those prescribed OAT previously (>3 months ago) compared with recently (aRR 1.74, 95% CI 1.11 to 2.71). CONCLUSIONS: The widening gap in vaccine coverage for those prescribed OAT, compared with the general population, is likely to have exacerbated the risk of severe COVID-19 in this population over the pandemic. However, continued OAT use may have provided protection from severe COVID-19 among those with opioid dependence.

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.

Interventions to prevent HIV and Hepatitis C among people who inject drugs: Latest evidence of effectiveness from a systematic review (2011 to 2020).

BACKGROUND: Hepatitis C virus (HCV) and HIV remain prevalent among people who inject drugs (PWID) and transmission is usually associated with injecting risk behaviour (IRB). We update a 2011 review of reviews (RoR) to assess the latest evidence on the effectiveness of harm reduction interventions - drug treatment (including opioid agonist therapy [OAT]), needle and syringe programmes (NSP) and other interventions - in the prevention of HCV and HIV transmission, and related measures of infection risk (IRB and injecting frequency [IF]), among PWID. METHODS: We undertook an initial search for systematic reviews (i.e. an Overview of Reviews [OoR]) and subsequent systematic searches for primary studies where required. Where there was sufficient evidence based on synthesis of multiple robust studies for an intervention effect in the 2011 RoR, new evidence was not sought. Medline, CINAHL, The Cochrane Library, EMBASE, PsycINFO and Web of Science were searched (2011-2020). Two reviewers screened papers, extracted data, and graded reviews/studies. We classified evidence as 'sufficient', 'tentative', 'insufficient', or 'no evidence'. RESULTS: We screened 8513 reviews and 7133 studies, with 27 and 61 identified as relevant, respectively. The level of evidence increased since the 2011 RoR and is now 'sufficient' for OAT (regarding all outcomes), NSP (for reducing HIV transmission and IRB), and combination OAT/NSP (for reducing HCV transmission). There is also now sufficient evidence for in-prison OAT, psychosocial interventions, pharmacy-based NSP and provision of sterile drug preparation equipment for reducing IRB. CONCLUSION: There is now a strong body of empirical evidence for the effectiveness of OAT and NSP, alone and in combination, in reducing IRB, and HCV and HIV transmission. However, there is still a relative lack of evidence for other interventions, including heroin-assisted treatment, pharmacological treatment for stimulant dependence, contingency management, technology-based interventions, low dead space syringes and drug consumption rooms on HCV or HIV risk.

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.

The uptake of foil from needle and syringe provision services and its role in smoking or snorting heroin among people who inject drugs in Scotland.

BACKGROUND: In the UK, legislation was implemented in 2014 allowing needle and syringe provision (NSP) services to offer foil to people who inject drugs (PWID) to encourage smoking rather than injecting. This paper aims to examine the association between foil uptake and smoking or snorting heroin among PWID. This is the first large scale national study to examine foil uptake and smoking or snorting heroin among PWID post legislative change. METHOD: Data from 1453 PWID interviewed via Scotland's Needle Exchange Surveillance Initiative in 2017-2018 were analysed using multivariate logistic regression. RESULTS: Overall, 36% of PWID had obtained foil from NSP services in the past six months. The odds of smoking or snorting heroin were higher among those who had obtained foil (Adjusted Odds Ratio (AOR) 3.79 (95% CI 2.98-4.82) p<0.001) compared to those who had not. Smoking or snorting heroin was associated with lower odds of injecting four or more times daily (AOR 0.60 (95% CI 0.40-0.90) p = 0.012) and injecting into the groin or neck (AOR 0.57 (95% CI 0.46-0.71) p<0.001) but increased odds of having had a skin and soft tissue infection (SSTI) (AOR 1.49 (95% CI 1.17-1.89) p = 0.001) and having experienced an overdose (AOR 1.58 (95% CI 1.18-2.10) p = 0.002) both in the past year. CONCLUSION: The promotion of smoking drugs via foil provision from NSP services may contribute to the package of harm reduction measures for PWID alongside the provision of injecting equipment. We found that those in receipt of foil were more likely to smoke or snort heroin, and that smoking or snorting heroin was associated with a lower likelihood of some risky injecting behaviours, namely frequent injecting and injecting into the groin or neck. But it remains uncertain if the provision of foil can lead to a reduction in health harms, such as SSTI and overdose. Future research is needed to understand PWID motivations for smoking drugs, obtaining foil from NSP services, and its uses particularly among polydrug users.

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.

Severe Acute Respiratory Syndrome Coronavirus 2 Serosurveillance in a Patient Population Reveals Differences in Virus Exposure and Antibody-Mediated Immunity According to Host Demography and Healthcare Setting.

Identifying drivers of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) exposure and quantifying population immunity is crucial to prepare for future epidemics. We performed a serial cross-sectional serosurvey throughout the first pandemic wave among patients from the largest health board in Scotland. Screening of 7480 patient serum samples showed a weekly seroprevalence ranging from 0.10% to 8.23% in primary and 0.21% to 17.44% in secondary care, respectively. Neutralization assays showed that highly neutralizing antibodies developed in about half of individuals who tested positive with enzyme-linked immunosorbent assay, mainly among secondary care patients. We estimated the individual probability of SARS-CoV-2 exposure and quantified associated risk factors. We show that secondary care patients, male patients, and 45-64-year-olds exhibit a higher probability of being seropositive. The identification of risk factors and the differences in virus neutralization activity between patient populations provided insights into the patterns of virus exposure during the first pandemic wave and shed light on what to expect in future waves.

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.

Comparison of SARS-CoV-2 serological assays for use in epidemiological surveillance in Scotland.

Background: Sero-surveillance of SARS-CoV-2 is crucial to monitoring levels of population exposure and informing public health responses, but may be influenced by variability in performance between available assays. Methods: Five commercial immunoassays and a neutralising activity assay were used to detect antibodies to SARS-CoV-2 in routine primary care and paediatric samples collected during the first wave of the pandemic in NHS Lothian, Scotland as part of ongoing surveillance efforts. For each assay, sensitivity and specificity was calculated relative to consensus results (majority of immunoassays positive = overall positive) and neutralising activity. Quantitative correlation was performed between serological and neutralising titres. Results: Seroprevalence ranged from 3.4-7.3 % in primary care patients and 3-5.9 % in paediatric patients according to different immunoassays. Neutralising activity was detectable in 2.8 % and 1.3 % respectively. Relative assay performance changed depending on comparison to immunoassay consensus versus neutralising activity and qualititative versus quantitative agreement. Cross-reactivity with endemic seasonal coronaviruses was confirmed by neutralising assay in false positives for one immunoassay. Presence of false positives for another assay was found specifically in paediatric but not adult samples. Conclusions: Five serological assays show variable accuracy when applied to the general population, impacting seroprevalence estimates. Assay performance may also vary in detection of protective neutralising antibody levels. These aspects should be considered in assay selection and interpretation in epidemiological studies.

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.