Utilising Integrated Bio-behavioural Surveillance (IBBS) to investigate declining hepatitis C antibody prevalence among people who inject drugs in the Australian Needle and Syringe Program Survey.

BACKGROUND: Prevalence of hepatitis C virus (HCV) antibody (Ab) on dried blood spot (DBS) samples in the Australian Needle and Syringe Program Survey (ANSPS) decreased nationally from 57% in 2015 to 32% in 2022. We aimed to investigate potential explanations for this decline. METHODS: Changes in DBS HCV Ab prevalence were investigated by redefining positive cases as those with those with either a positive HCV Ab test result or a self-reported history of ever having HCV treatment (modified prevalence), examining HCV Ab prevalence by birth and age cohorts, and assessing trends in key risk behaviours. RESULTS: Overall prevalence of DBS HCV Ab declined rapidly and significantly from 57% in 2015 to 32% in 2022 (p<0.001) however modified HCV Ab prevalence remained stable over time (85% and 88% in 2015 and 2022, respectively, p=0.357). The proportion of participants with negative HCV Ab and self-reported HCV infection increased from 20% in 1995 to 40% in 2022 (p<0.001) and the proportion with negative HCV Ab and lifetime HCV treatment increased from 3% in 1999 to 67% in 2022 (p<0.001). We also observed a decreasing trend in DBS HCV Ab prevalence in all birth and age cohorts with a noticeable acceleration in the decline commensurate with the advent of HCV DAA treatment. A long-term decreasing trend was also observed for key risk behaviours (p<0.001) however the short-term trend was not significant for recent receptive syringe sharing. CONCLUSION: The temporal decline in HCV Ab prevalence appears related to reduced sensitivity of DBS HCV Ab detection with viral clearance following treatment. Since 2016, HCV treatment uptake has increased markedly including among people who inject drugs. In this context, continuing to monitor HCV Ab prevalence by DBS testing is problematic, with a shift to surveillance of active infection the most relevant to guide policy and practice in this setting.

Clinical effectiveness and analytical quality of a national point-of-care testing network for sexually transmitted infections integrated into rural and remote primary care clinics in Australia, 2016-2022: an observational program evaluation.

Background: To address inequitable diagnostic access and improve time-to-treatment for First Nations peoples, molecular point-of-care (POC) testing for chlamydia, gonorrhoea and trichomonas was integrated into 49 primary care clinics across Australia. We conducted an observational evaluation to determine clinical effectiveness and analytical quality of POC testing delivered through this national program. Methods: We evaluated (i) implementation by measuring trends in mean monthly POC testing; ii) clinical effectiveness by comparing proportions of positive patients treated by historical control/intervention period and by test type, and calculated infectious days averted; (iii) analytical quality by calculating result concordance by test type, and proportion of unsuccessful POC tests. Findings: Between 2016 and 2022, 46,153 POC tests were performed; an increasing mean monthly testing trend was observed in the first four years (p < 0.0001). A greater proportion of chlamydia/gonorrhoea positives were treated in intervention compared with historical control periods (≤2 days: 37% vs 22% [RR 1.68; 95% CI 1.12, 2.53]; ≤7 days: 48% vs 30% [RR 1.6; 95% CI 1.10, 2.33]; ≤120 days: 79% vs 54% [RR 1.46; 95% CI 1.10, 1.95]); similarly for trichomonas positives and by test type. POC testing for chlamydia, gonorrhoea and trichomonas averted 4930, 5620 and 7075 infectious days, respectively. Results concordance was high [99.0% (chlamydia), 99.3% (gonorrhoea) and 98.9% (trichomonas)]; unsuccessful POC test proportion was 1.8% for chlamydia/gonorrhoea and 2.1% for trichomonas. Interpretation: Molecular POC testing was successfully integrated into primary care settings as part of a routinely implemented program achieving significant clinical benefits with high analytical quality. In addition to the individual health benefits of earlier treatment, fewer infective days could contribute to reduced transmissions in First Nations communities. Funding: This work was supported by an Australian National Health and Medical Research Council Partnership Grant (APP1092503), the Australian Government Department of Health, Western Australia and Queensland Departments of Health.

B-cell characteristics define HCV reinfection outcome.

BACKGROUND & AIMS: In individuals highly exposed to HCV, reinfection is common, suggesting that natural development of sterilising immunity is difficult. In those that are reinfected, some will develop a persistent infection, while a small proportion repeatedly clear the virus, suggesting natural protection is possible. The aim of this study was to characterise immune responses associated with rapid natural clearance of HCV reinfection. METHODS: Broad neutralising antibodies (nAbs) and Envelope 2 (E2)-specific memory B cell (MBC) responses were examined longitudinally in 15 individuals with varied reinfection outcomes. RESULTS: Broad nAb responses were associated with MBC recall, but not with clearance of reinfection. Strong evidence of antigen imprinting was found, and the B-cell receptor repertoire showed a high level of clonality with ongoing somatic hypermutation of many clones over subsequent reinfection events. Single-cell transcriptomic analyses showed that cleared reinfections featured an activated transcriptomic profile in HCV-specific B cells that rapidly expanded upon reinfection. CONCLUSIONS: MBC quality, but not necessarily breadth of nAb responses, is important for protection against antigenically diverse variants, which is encouraging for HCV vaccine development. IMPACT AND IMPLICATIONS: HCV continues to have a major health burden globally. Limitations in the health infrastructure for diagnosis and treatment, as well as high rates of reinfection, indicate that a vaccine that can protect against chronic HCV infection will greatly complement current efforts to eliminate HCV-related disease. With alternative approaches to testing vaccines, such as controlled human inoculation trials under consideration, we desperately need to identify the correlates of immune protection. In this study, in a small but rare cohort of high-risk injecting drug users who were reinfected multiple times, breadth of neutralisation was not associated with ultimate clearance of the reinfection event. Alternatively, characteristics of the HCV-specific B-cell response associated with B-cell proliferation were. This study indicates that humoral responses are important for protection and suggests that for genetically very diverse viruses, such as HCV, it may be beneficial to look beyond just antibodies as correlates of protection.

High COVID-19 vaccine uptake following initial hesitancy among people in Australia who inject drugs.

BACKGROUND: Previous studies have reported high COVID-19 vaccine hesitancy among people who inject drugs. We aimed to examine COVID-19 vaccine coverage, motivations and barriers to vaccination, and factors associated with uptake among this population in Australia, 1.5 years after vaccine rollout commenced. METHODS: In June-July 2022, 868 people (66.0 % male, mean age 45.6 years) who regularly inject drugs and reside in an Australian capital city reported the number of COVID-19 vaccine doses they had received and their primary motivation (if vaccinated) or barrier (if unvaccinated) to receive the vaccine. We compared vaccine uptake to Australian population estimates and used logistic regression to identify factors associated with ≥ 2 dose and ≥ 3 dose uptake. RESULTS: Overall, 84.1 % (n = 730) had received at least one COVID-19 vaccine dose, 79.6 % (n = 691) had received ≥ 2 doses, and 46.1 % (n = 400) had received ≥ 3 doses. Participants were less likely to be vaccinated than the Australian general population (prevalence ratio: 0.82, 95 % confidence interval [CI]: 0.76-0.88). Key motivations to receive the vaccine were to protect oneself or others from COVID-19, while barriers pertained to vaccine or government distrust. Opioid agonist treatment (adjusted odds ratio [aOR]: 2.49, 95 % CI: 1.44-4.42), current seasonal influenza vaccine uptake (aOR: 6.76, 95 % CI: 3.18-16.75), and stable housing (aOR: 1.58, 95 % CI: 1.02-2.80) were associated with receipt of at least two vaccine doses. Participants aged ≥ 40 years (versus < 40 years; aOR: 1.66, 95 % CI: 1.10-2.53) or who reported a chronic health condition (aOR: 1.71, 95 % CI: 1.18-2.47) had higher odds of receiving at least three vaccine doses. CONCLUSION: We observed higher COVID-19 vaccine uptake than expected given previous studies of vaccine acceptability among people who inject drugs. However, it was lower than the general population. People who inject drugs and reside in unstable housing are a subpopulation that require support to increase vaccine uptake.

Characterization of antibody-dependent cellular phagocytosis in patients infected with hepatitis C virus with different clinical outcomes.

Early neutralizing antibodies against hepatitis C virus (HCV) and CD8 + T cell effector responses can lead to viral clearance. However, these functions alone are not sufficient to protect patients against HCV infection, thus undefined additional antiviral immune mechanisms are required. In recent years, Fc-receptor-dependent antibody effector functions, particularly, antibody-dependent cellular phagocytosis (ADCP) were shown to offer immune protection against several RNA viruses. However, its development and clinical role in patients with HCV infection remain unknown. In this study, we found that patients with chronic GT1a or GT3a HCV infection had significantly higher concentrations of anti-envelope 2 (E2) antibodies, predominantly IgG1 subclass, than patients that cleared the viruses while the latter had antibodies with higher affinities. 97% of the patients with HCV had measurable ADCP of whom patients with chronic disease showed significantly higher ADCP than those who naturally cleared the virus. Epitope mapping studies showed that patients with antibodies that target antigenic domains on the HCV E2 protein that are known to associate with neutralization function are also strongly associated with ADCP, suggesting antibodies with overlapping/dual functions. Correlation studies showed that ADCP significantly correlated with plasma anti-E2 antibody levels and neutralization function regardless of clinical outcome and genotype of infecting virus, while a significant correlation between ADCP and affinity was only evident in patients that cleared the virus. These results suggest ADCP was mostly driven by antibody titer in patients with chronic disease while maintained in clearers due to the quality (affinity) of their anti-E2 antibodies despite having lower antibody titers.

Parents who inject drugs: Demographics, care arrangements and correlates for child placement in out-of-home care.

INTRODUCTION: Children in families affected by substance use disorders are at high risk of being placed in out-of-home care (OOHC). We aimed to describe the characteristics of parents who inject drugs and identify correlates associated with child placement in OOHC. METHODS: We used baseline data from a community-based cohort of parents who inject drugs (SuperMIX) from Melbourne, Australia. Participants were recruited via convenience, respondent-driven and snowball sampling from April 2008 to November 2020, with follow-up until March 2021. To explore correlates associated with child placement to OOHC, we used multivariable logistic regression and assessed for potential interactions between gender and a range of relevant covariates. RESULTS: Of the 1067 participants, 611 (57%) reported being parents. Fifty-six percent of parents reported child protection involvement. Almost half (49%) had children in OOHC. Nearly half of the parents lived in unstable accommodation (44%) and many of them experienced moderate-severe levels of anxiety (48%) and depression (53%). Female or non-binary gender, identifying as Aboriginal or Torres Strait Islander, experiencing assault and having more children were associated with child removal to OOHC. Of the 563 participants who reported their own childhood care status, 135 (24%) reported they had been removed to OOHC. DISCUSSION AND CONCLUSIONS: We identified high rates of child placement in OOHC among parents who inject drugs. There is a need for targeted health and social services, that are gender and culturally responsive, in addition to systems-level interventions addressing social inequities, such as housing, to support parents to care for their children.

The gendered violence of injecting-related stigma among relatively affluent, suburban women who inject drugs.

INTRODUCTION: In honouring the legacy of Jude Byrne's life-long advocacy for women and mothers who use drugs, this paper presents a case study of a group of women about whom we know little about and hear even less from: women who inject drugs in relatively affluent suburbs. METHODS: Based on a 2020 qualitative study of people who inject drugs in an affluent area of Sydney known as 'The Beaches', we use in-depth interview data to thematically explore the lived experiences of gendered stigma among women who inject drugs. RESULTS: Even when women occupy the 'ideal' social position in terms of class (middle-class) and race (White) they remain subject to harmful forms of gendered stigma related to injecting drug use. Participants had internalised negative attitudes around injection drug use as a form of failed femininity and, despite being part of 'good' families and neighbourhoods, participants experienced forced child removal. DISCUSSION AND CONCLUSIONS: Taking the lead from feminist intersectionality scholarship, our data illustrate how stigma and discrimination act as a form of structural violence against women who inject drugs in affluent communities. While the social relations of gender provide some degree of protection by 'performing proximity to Whiteness', gendered stigma and violence persist.

Prevalence and incidence of emergency department presentations and hospital separations with injecting-related infections in a longitudinal cohort of people who inject drugs.

People who inject drugs are at risk of acute bacterial and fungal injecting-related infections. There is evidence that incidence of hospitalizations for injecting-related infections are increasing in several countries, but little is known at an individual level. We aimed to examine injecting-related infections in a linked longitudinal cohort of people who inject drugs in Melbourne, Australia. A retrospective descriptive analysis was conducted to estimate the prevalence and incidence of injecting-related infections using administrative emergency department and hospital separation datasets linked to the SuperMIX cohort, from 2008 to 2018. Over the study period, 33% (95%CI: 31-36%) of participants presented to emergency department with any injecting-related infections and 27% (95%CI: 25-30%) were admitted to hospital. Of 1,044 emergency department presentations and 740 hospital separations, skin and soft tissue infections were most common, 88% and 76%, respectively. From 2008 to 2018, there was a substantial increase in emergency department presentations and hospital separations with any injecting-related infections, 48 to 135 per 1,000 person-years, and 18 to 102 per 1,000 person-years, respectively. The results emphasize that injecting-related infections are increasing, and that new models of care are needed to help prevent and facilitate early detection of superficial infection to avoid potentially life-threatening severe infections.

Injection Drug Use Frequency Before and After Take-Home Naloxone Training.

Importance: Concerns that take-home naloxone (THN) training may lead to riskier drug use (as a form of overdose risk compensation) remain a substantial barrier to training implementation. However, there was limited good-quality evidence in a systematic review of the association between THN access and subsequent risk compensation behaviors. Objective: To assess whether THN training is associated with changes in overdose risk behaviors, indexed through injecting frequency, in a cohort of people who inject drugs. Design, Setting, and Participants: This cohort study used prospectively collected self-reported behavioral data before and after THN training of participants in The Melbourne Injecting Drug User Cohort Study (SuperMIX). Annual interviews were conducted in and around Melbourne, Victoria, Australia, from 2008 to 2021. SuperMIX participants were adults who regularly injected heroin or methamphetamine in the 6 months preceding their baseline interview. The current study included only people who inject drugs who reported THN training and had participated in at least 1 interview before THN training. Exposure: In 2017, the SuperMIX baseline or follow-up survey began asking participants if and when they had received THN training. The first THN training date that was recorded was included as the exposure variable. Subsequent participant interviews were excluded from analysis. Main Outcomes and Measures: Injecting frequency was the primary outcome and was used as an indicator of overdose risk. Secondary outcomes were opioid injecting frequency, benzodiazepine use frequency, and the proportion of the time drugs were used alone. Fixed-effects generalized linear (Poisson) multilevel modeling was used to estimate the association between THN training and the primary and secondary outcomes. Time-varying covariates included housing status, income, time in study, recent opioid overdose, recent drug treatment, and needle and syringe coverage. Findings were expressed as incidence rate ratios (IRRs) with 95% CIs. Results: There were 1328 participants (mean [SD] age, 32.4 [9.0] years; 893 men [67.2%]) who completed a baseline interview in the SuperMIX cohort, and 965 participants completed either a baseline or follow-up interview in or after 2017. Of these 965 participants, 390 (40.4%) reported THN training. A total of 189 people who inject drugs had pretraining participant interviews with data on injecting frequency and were included in the final analysis (mean [SD] number of interviews over the study period, 6.2 [2.2]). In fixed-effects regression analyses adjusted for covariates, there was no change in the frequency of injecting (IRR, 0.91; 95% CI, 0.69-1.20; P = .51), opioid injecting (IRR, 0.95; 95% CI, 0.74-1.23; P = .71), benzodiazepine use (IRR, 0.96; 95% CI, 0.69-1.33; P = .80), or the proportion of reported time of using drugs alone (IRR, 1.04; 95% CI, 0.86-1.26; P = .67) before and after THN training. Conclusions and Relevance: This cohort study of people who inject drugs found no evidence of an increase in injecting frequency, along with other markers of overdose risk, after THN training and supply. The findings suggest that THN training should not be withheld because of concerns about risk compensation and that advocacy for availability and uptake of THN is required to address unprecedented opioid-associated mortality.

The impacts of COVID-19 measures on drug markets and drug use among a cohort of people who use methamphetamine in Victoria, Australia.

BACKGROUND AND AIMS: Few studies of the impacts of the coronavirus disease 2019 (COVID-19) public health measures on drug markets and drug use patterns have used longitudinal data. We aimed to examine whether COVID-19 measures were associated with increases in methamphetamine price, decreases in methamphetamine use frequency and subsequent changes in secondary outcomes of other drug use frequency in metropolitan Melbourne and regional Victoria. DESIGN: Longitudinal analysis framework was used from a longitudinal cohort of people who use methamphetamine. SETTING: Victoria state, Australia. PARTICIPANTS: One hundred eighty-five VMAX study participants who reported a methamphetamine purchase after the onset of the pandemic were used for the price paid analysis. Methamphetamine or other drug use frequency analysis was performed using 277 participants who used methamphetamine during the pandemic or in the year before the pandemic. MEASUREMENTS: Price paid per gram of methamphetamine derived from the most recent purchase price and most recent purchase quantity. Frequency of methamphetamine and other drug use measured as the average number of days per week used in the last month. FINDINGS: Compared with pre-COVID-19 period, methamphetamine prices increased by AUD351.63 (P value <0.001) and by AUD456.51 (P value <0.001) in Melbourne and regional Victoria, respectively, during the period in which the most intense public health measures were implemented in Victoria. Although prices decreased after harder restrictions were lifted (by AUD232.84, P value <0.001 and AUD263.68, P value <0.001, in Melbourne and regional Victoria, respectively), they remained higher than pre-COVID-19 levels. A complementary 76% decrease was observed in relation to methamphetamine use frequency in regional Victoria (P value = 0.006) that was not offset by any changes in the frequency of use of other drugs such as alcohol, tobacco or other illicit drugs. CONCLUSION: COVID-19 public health measures in Victoria state, Australia, appear to have been associated with major price changes in the methamphetamine market and decreased frequency of use of the drug.

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.

COVID-19 vaccine attitudes and facilitators among people in Australia who inject drugs.

INTRODUCTION: We aimed to describe COVID-19 vaccination attitudes and identify potential facilitators for vaccine uptake among people who inject drugs. METHODS: People who inject drugs were recruited from all eight Australian capital cities (N = 884; 65% male, mean age 44 years) and interviewed face-to-face or via telephone in June-July 2021. COVID-19 and broader vaccination attitudes were used to model latent classes. Correlates of class membership were assessed through multinomial logistic regression. Probability of endorsing potential vaccination facilitators were reported by class. RESULTS: Three classes of participants were identified: 'vaccine acceptant' (39%), 'vaccine hesitant' (34%) and 'vaccine resistant' (27%). Those in the hesitant and resistant groups were younger, more likely to be unstably housed and less likely to have received the current season influenza vaccine than the acceptant group. In addition, hesitant participants were less likely to report a chronic medical condition than acceptant participants. Compared to vaccine acceptant and hesitant participants, vaccine-resistant participants were more likely to predominantly inject methamphetamine and to inject drugs more frequently in the past month. Both vaccine-hesitant and resistant participants endorsed financial incentives for vaccination and hesitant participants also endorsed facilitators related to vaccine trust. DISCUSSION AND CONCLUSION: People who inject drugs who are unstably housed or predominantly inject methamphetamine are subgroups that require targeted interventions to increase COVID-19 vaccination uptake. Vaccine-hesitant people may benefit from interventions that build trust in vaccine safety and utility. Financial incentives may improve vaccine uptake among both hesitant and resistant people.

Long-term trends in human body size track regional variation in subsistence transitions and growth acceleration linked to dairying.

Evidence for a reduction in stature between Mesolithic foragers and Neolithic farmers has been interpreted as reflective of declines in health, however, our current understanding of this trend fails to account for the complexity of cultural and dietary transitions or the possible causes of phenotypic change. The agricultural transition was extended in primary centers of domestication and abrupt in regions characterized by demic diffusion. In regions such as Northern Europe where foreign domesticates were difficult to establish, there is strong evidence for natural selection for lactase persistence in relation to dairying. We employ broad-scale analyses of diachronic variation in stature and body mass in the Levant, Europe, the Nile Valley, South Asia, and China, to test three hypotheses about the timing of subsistence shifts and human body size, that: 1) the adoption of agriculture led to a decrease in stature, 2) there were different trajectories in regions of in situ domestication or cultural diffusion of agriculture; and 3) increases in stature and body mass are observed in regions with evidence for selection for lactase persistence. Our results demonstrate that 1) decreases in stature preceded the origins of agriculture in some regions; 2) the Levant and China, regions of in situ domestication of species and an extended period of mixed foraging and agricultural subsistence, had stable stature and body mass over time; and 3) stature and body mass increases in Central and Northern Europe coincide with the timing of selective sweeps for lactase persistence, providing support for the "Lactase Growth Hypothesis."

Comprehensive needle and syringe program and opioid agonist therapy reduce HIV and hepatitis c virus acquisition among people who inject drugs in different settings: A pooled analysis of emulated trials.

BACKGROUND AND AIMS: Although the Netherlands, Canada and Australia were early adopters of harm reduction for people who inject drugs (PWID), their respective HIV and hepatitis C (HCV) epidemics differ. We measured the pooled effect of needle and syringe program (NSP) and opioid agonist therapy (OAT) participation on HIV and HCV incidence in these settings. DESIGN: For each cohort, we emulated the design and statistical analysis of a target trial using observational data. SETTING AND PARTICIPANTS: We included PWID at risk of HIV or HCV infection from the Amsterdam Cohort Studies (1985-2013), Vancouver Injection Drug Users Study (1997-2009) and Melbourne Injecting Drug User Cohort Study (SuperMIX) (2010-2021). MEASUREMENTS: Separately for each infection and cohort (only HCV in SuperMIX), marginal structural models were used to compare the effect of comprehensive (on OAT and 100% NSP coverage or on OAT only if no recent injection drug use) versus no/partial NSP/OAT (no OAT and/or <100% NSP coverage) participation. Pooled hazard ratios (HR) and 95% CI were calculated using random-effects meta-analysis. FINDINGS: We observed 94 HIV seroconversions and 81 HCV seroconversions among 2023 and 430 participants, respectively. Comprehensive NSP/OAT led to a 41% lower risk of HIV acquisition (pooled HR = 0.59, 95% CI = 0.36-0.96) and a 76% lower risk of HCV acquisition (pooled HR = 0.24, 95% CI = 0.11-0.51), compared with no/partial NSP/OAT, with little heterogeneity between studies for both infections (I2  = 0%). CONCLUSIONS: In the Netherlands, Canada and Australia, comprehensive needle and syringe program and opioid agonist therapy participation appears to substantially reduce HIV and hepatitis C acquisition compared with no or partial needle and syringe program/opioid agonist therapy participation. These findings from an emulated trial design reinforce the critical role of comprehensive access to harm reduction in optimizing infection prevention for people who inject drugs.

Injection drug use in an affluent beachside community in Sydney: An exploratory qualitative study.

INTRODUCTION: Social research on injection drug use has focussed on marginalised groups and communities, leaving a large gap in the field's understanding of how it is experienced in other settings, including in relatively affluent communities. METHODS: This research is based on fieldwork and 18 in-depth qualitative interviews conducted in suburban beach-side communities in Sydney collectively known as the Northern Beaches. RESULTS: Participants did not experience stigmatisation by local health services as the norm or as a deterrent to access. Drug acquisition on the Northern Beaches occurred among closed networks of friends and acquaintances, and injecting use rarely occurred in public settings. Police contact was minimal, resulting in lower levels of criminalisation. DISCUSSION AND CONCLUSIONS: Unlike many of the participants featured in the literature, our study participants grew up in middle and upper middle-class households, typically experiencing comfortable childhoods with little to no exposure to injection drug use. In this setting injection drug use operates covertly within the normal rhythms of middle-class life, hidden in amongst the bustle of cafés and shopping centres, and through the friendliness of neighbourhood driveway and doorstep interactions. Drug use is described as common in the area, with injecting behaviours stigmatised in ways that set it against the 'good' families and neighbourhoods of this beach-side enclave. In contrast to much of the Australian qualitative literature which frames injection drug use as a means of psychological relief or a subcultural norm, our participants described injecting as motivated by the desire to enhance pleasure and social connection.

Incidence of primary hepatitis C virus infection among people who inject drugs in Australia pre- and post-unrestricted availability of direct acting antiviral therapies.

AIMS: The 2016 Global Health Sector Strategy (GHSS) on viral hepatitis aims to reduce new hepatitis C virus (HCV) infections by 80% by 2030, including a 30% reduction by 2020. This study aimed to estimate primary HCV incident infection among a national sample of people who inject drugs (PWID) before and after the introduction of unrestricted access to HCV direct-acting antiviral (DAA) therapy via Australia's Pharmaceutical Benefits Scheme in 2016. DESIGN: A simple deterministic linkage method identified repeat respondents in serial cross-sectional surveys conducted among PWID. Two separate retrospective cohorts of HCV antibody-negative respondents were created, corresponding to the pre- (2010-15) and post- (2016-21) DAA time-periods. SETTING AND PARTICIPANTS: This study took place in Australia. Among 757 PWID retained (376 pre-DAA, 381 post-DAA), more than half were male (60%), the majority were heterosexual (80%), the median age was 40 years (interquartile range = 33-46 years) and the predominant drugs last injected were heroin (24%), pharmaceutical opioids (27%) and methamphetamine (41%). MEASUREMENTS: The primary outcome was HCV seroconversion, defined as a negative HCV antibody test result followed by a positive HCV antibody result. Time to primary incident HCV infection was estimated using the person-years (PY) method. FINDINGS: A total 97 of 376 (2010-15) and 41 of 381 (2016-21) HCV seroconversions were identified. Primary HCV incidence more than halved, from 13.6 per 100 PY [95% confidence intervals (CI) = 11.2, 16.6] in 2010-15 to 5.4 per 100 PY (95% CI = 3.9, 7.3) in 2016-21. The decline was independent of observed differences in demographic and drug use characteristics over the two time-periods (adjusted hazard ratio = 0.47, 95% CI = 0.31-0.69, P < 0.001). CONCLUSIONS: Australia has had a 53% reduction in primary hepatitis C virus (HCV) incidence among people who inject drugs following unrestricted availability of HCV direct acting antiviral therapy in March 2016. Given that PWID are the predominant population at risk of HCV infection in Australia, findings add to the evidence that Australia has probably met its 2020 Global Health Sector Strategy subtarget of a 30% decline in new infections.