Direct-acting antiviral therapies for hepatitis C infection: global registration, reimbursement, and restrictions.

Direct-acting antivirals (DAAs) for hepatitis C virus (HCV) infection have delivered high response rates (>95%) and simplified the management of HCV treatment, permitting non-specialists to manage patients without advanced liver disease. We collected and reviewed global data on the registration and reimbursement (government subsidised) of HCV therapies, including restrictions on reimbursement. Primary data collection occurred between Nov 15, 2021, and July 24, 2023, through the assistance of a global network of 166 HCV experts. We retrieved data for 160 (77%) of 209 countries and juristrictions. By mid-2023, 145 (91%) countries had registered at least one of the following DAA therapies: sofosbuvir-velpatasvir, sofosbuvir-velpatasvir-voxilaprevir, glecaprevir-pibrentasvir, sofosbuvir-daclatasvir, or sofosbuvir. 109 (68%) countries reimbursed at least one DAA therapy. Among 102 low-income and middle-income countries (LMICs), 89 (87%) had registered at least one HCV DAA therapy and 53 (52%) reimbursed at least one DAA therapy. Among all countries with DAA therapy reimbursement (n=109), 66 (61%) required specialist prescribing, eight (7%) had retreatment restrictions, seven (6%) had an illicit drug use restriction, five (5%) had an alcohol use restriction, and three (3%) had liver disease restrictions. Global access to DAA reimbursement remains uneven, with LMICs having comparatively low reimbursement compared with high-income countries. To meet WHO goals for HCV elimination, efforts should be made to assist countries, particularly LMICs, to increase access to DAA reimbursement and remove reimbursement restrictions-especially prescriber-type restrictions-to ensure universal access.

Prevalence of childhood maltreatment among people with opioid use disorder: A systematic review and meta-analysis.

BACKGROUND: Experience of childhood maltreatment (CM) is a risk factor for opioid use disorder (OUD). CM is also associated with comorbid mental disorders and poor treatment outcomes among people with OUD. To our knowledge, this is the first systematic review and meta-analysis to estimate the prevalence of CM among people with OUD. METHODS: We searched MEDLINE, EMBASE, and PsycINFO to identify observational studies that evaluated CM among people with OUD from January 1990 to June 2020. Prevalence of each CM type, sample characteristics, and methodological factors were extracted from each eligible study. Random-effects meta-analyses were used to pool prevalence estimates. Stratified meta-analyses were used to assess heterogeneity. RESULTS: Of the 6,438 publications identified, 113 studies reported quantitative CM data among people with OUD and 62 studies (k = 62; N = 21,871) were included in primary analyses. Among people with OUD, the estimated prevalence of sexual abuse was 41% (95% CI 36-47%; k = 38) among women and 16% (95% CI 12-20%; k = 25) among men. Among all people with OUD, prevalence estimates were 38% (95% CI 33-44%; k = 48) for physical abuse, 43% (95% CI 38-49%; k = 31) for emotional abuse, 38% (95% CI 30-46%; k = 17) for physical neglect, and 42% (95% CI 32-51%; k = 17) for emotional neglect. Sex, history of injecting drug use, recruitment methods, and method of assessing CM were associated with substantial heterogeneity. CONCLUSIONS: People with OUD frequently report the experience of CM, supporting the need for trauma-informed interventions among this population. Future research should consider the impact of CM on OUD presentations and when assessment is appropriate, use of validated instruments.

Opioid overdose risk during and after drug treatment for heroin dependence: An incidence density case-control study nested in the VEdeTTE cohort.

INTRODUCTION AND AIMS: To corroborate protective effects of a range of drug treatment modalities against overdose mortality risk. DESIGN AND METHODS: Nested case-control study, with incidence density sampling, selecting controls retrospectively at each case event. Cases and controls came from a sub-cohort of opioid-dependent patients (n = 4444) from two Italian regions (Lazio and Piedmont). From 1998 to 2005, there were 91 overdose deaths (cases) matched to 352 controls. The primary outcome was overdose mortality and the primary exposure was drug treatment: opioid agonist treatment (OAT), opioid detoxification, residential community, psychosocial and other pharmacological treatment. Conditional logistic regression models generated intervention effects comparing mortality risk in and out of treatment, adjusting for confounding variables. RESULTS: Overall, drug treatment reduced overdose mortality risk by 80% [adjusted odds ratio (AOR) 0.18, 95% confidence interval (CI) 0.10-0.33, P < 0.001] compared to being out of treatment. There was a particularly strong protective effect of OAT on overdose mortality (AOR 0.08, 95% CI 0.03-0.23, P < 0.001) compared to being out of treatment. There was evidence of a substantially elevated risk of overdose in the first month of leaving treatment (AOR 23.50, 95% CI 7.84-70.19, P < 0.001) compared to being in treatment. DISCUSSION AND CONCLUSIONS: The nested case-control design strengthened earlier findings that OAT in Italy has strong protective effects on overdose mortality risk, much stronger than has been previously seen in other Western European settings.

Profile and correlates of injecting-related injuries and diseases among people who inject drugs in Australia.

INTRODUCTION: People who inject drugs (PWID) commonly experience harms related to their injecting, many of which are consequences of modifiable drug use practices. There is currently a gap in our understanding of how certain injecting-related injuries and diseases (IRID) cluster together, and socio-demographic and drug use characteristics associated with more complex clinical profiles. METHOD: Surveys were conducted with 902 Australian PWID in 2019. Participants provided information regarding their drug use, and past month experience of the following IRID: artery injection, nerve damage, skin and soft tissue infection, thrombophlebitis, deep vein thrombosis, endocarditis, septic arthritis, osteomyelitis, and septicaemia. We performed a latent class analysis, grouping participants based on reported IRID and ran a class-weighted regression analysis to determine variables associated with class-membership. RESULTS: One-third (34 %) of the sample reported any IRID. A 3-class model identified: 1) no IRID (73 %), moderate IRID (21 %), and 3) high IRID (6%) clusters. Re-using one`s own needles was associated with belonging to the high IRID versus moderate IRID class (ARRR = 2.38; 95 % CI = 1.04-5.48). Other factors, including daily injecting and past 6-month mental health problems were associated with belonging to moderate and high IRID classes versus no IRID class. CONCLUSION: A meaningful proportion of PWID reported highly complex IRID presentations distinguished by the presence of thrombophlebitis and associated with greater re-use of needles. Increasing needle and syringe coverage remains critical in addressing the harms associated with injecting drug use and expanding the capacity of low-threshold services to address less severe presentations might aid in reducing IRID amongst PWID.

Injecting risk behaviours amongst people who inject drugs: A global multi-stage systematic review and meta-analysis.

BACKGROUND: Injecting risk behaviour, such as receptive sharing of injecting equipment and/or re-using one's equipment, is associated with bloodborne virus transmission and infections in people who inject drugs (PWID). We aimed to estimate prevalence and correlates of injecting risk behaviours amongst PWID. METHODS: We conducted a systematic review and meta-analyses to estimate country, regional, and global prevalences of injecting risk behaviours (including sharing or re-using needle/syringe and sharing other injecting equipment). Using meta-regression analyses, we determined associations between study- and country-level characteristics and receptive needle/syringe sharing. RESULTS: From 61,077 identified papers and reports and 61 studies from expert consutation, evidence on injecting risk behaviours was available for 464 studies from 88 countries. Globally, it is estimated that 17.9% (95%CI: 16.2-19.6%) of PWID engaged in receptive needle/syringe sharing at last injection, 23.9% (95%CI: 21.2-26.5%) in the past month, and 32.8% (95%CI: 28.6-37.0%) in the past 6-12 months. Receptive sharing of other injecting equipment was common. Higher prevalence of receptive needle/syringe sharing in the previous month was associated with samples of PWID with a lower proportion of females, shorter average injecting duration, a higher proportion with ≥daily injecting, and older studies. Countries with lower development index, higher gender inequality and lower NSP coverage had higher proportions reporting receptive needle/syringe sharing. CONCLUSIONS: High levels of injecting risk behaviours were observed amongst PWID globally, although estimates were only available for half of the countries with evidence of injecting drug use. There is a need for better capturing of injecting risk behaviours in these countries to inform implementation of harm reduction services and evaluate potential impacts of interventions to reduce risk.

Socio-demographic and ecological factors associated with anti-HCV prevalence in people who inject drugs: A systematic review.

BACKGROUND: The World Health Organization (WHO) aim to eliminate hepatitis C virus (HCV) as a public health threat by 2030. People who inject drugs (PWID) are a key risk group for HCV transmission globally. We explored socio-demographic and ecological variables associated with HCV antibody (anti-HCV) prevalence among samples of PWID. METHODS: We systematically searched for and screened journal articles and online reports published between January 2011 and June 2017. Serologically confirmed anti-HCV prevalence among PWID and other study-level socio-demographic variables were extracted. Country-level ecological indicators were sourced from online databases. We used generalized linear models to investigate associations between anti-HCV prevalence estimates and other study-level and country-level variables. RESULTS: There were 223 studies from 84 countries contributing 569 estimates of anti-HCV prevalence among PWID. Among study-level indicators, higher levels of anti-HCV prevalence were associated with higher HIV prevalence (B = 0.20; 95 % Confidence Interval [95 %CI] = 0.12, 0.29, p < 0.001) and year of data collection (B=-0.08; 95 %CI=-0.15, -0.02; p = 0.011). At a national level, higher Human Development Index scores (B=4.37; 95 %CI=0.12, 8.63, p = 0.044) were associated with higher levels of anti-HCV in samples. IMPLICATIONS: Serological surveillance data are increasingly available globally; however, there are still geographical gaps in quantification of HCV prevalence among PWID that must be addressed to inform efforts to achieve HCV elimination. Anti-HCV prevalence was lower in samples of PWID from countries with lower Human Development Index scores, which points to an opportunity to provide targeted intervention and potentially control transmission rates of infection in countries characterized by poor population health, education, and income.

Global systematic review and ecological analysis of HIV in people who inject drugs: National population sizes and factors associated with HIV prevalence.

BACKGROUND: People who inject drugs (PWID) are at elevated risk of HIV infection. Data on population sizes of PWID living with HIV are needed to inform the implementation of prevention, treatment and care programs. We estimated national population sizes of people who recently (past 12 months) injected drugs living with HIV and evaluated ecological associations with HIV prevalence in PWID. METHODS: We used national data on the prevalence of injecting drug use and of HIV among PWID, derived from systematic reviews, to estimate national population sizes of PWID living with HIV. Uncertainty was estimated using Monte Carlo simulation with 100,000 draws. We extracted data on sample characteristics from studies of HIV prevalence among PWID, and identified national indicators that have been observed or hypothesised to be associated with HIV prevalence in PWID. We used linear regression to evaluate associations between these variables and HIV prevalence in PWID. RESULTS: Four countries comprised 55% of the estimated global population of PWID living with HIV: Russia (572,500; 95% uncertainty interval (UI) 235,500-1,036,500); Brazil (462,000; 95% UI 283,500-674,500); China (316,500; 95% UI 171,500-493,500), and the United States (195,500; 95% UI 80,000-343,000). Greater anti-HCV prevalence and national income inequality were associated with greater HIV prevalence in PWID. CONCLUSION: The countries with the largest populations of PWID living with HIV will need to dramatically scale up prevention, treatment and care interventions to prevent further increases in population size. The association between anti-HCV prevalence and HIV prevalence among PWID corroborates findings that settings with increasing HCV should implement effective interventions to prevent HIV outbreaks. The association between income inequality and HIV among PWID reinforces the need to implement structural interventions alongside targeted individual-level strategies.

Frequency of injecting among people who inject drugs: A systematic review and meta-analysis.

BACKGROUND: People who inject drugs (PWID) do so at varying frequencies. More frequent injecting is associated with skin and soft tissue infection, blood borne viruses, and overdose. The aims of this review are to estimate the prevalence of injecting frequency among PWID and compare these estimates to current needle-syringe distribution coverage estimates, and identify socio-demographic and risk characteristics, and harms associated with daily or more injecting. METHODS: We conducted a systematic review of the peer-reviewed and grey literature from 2008 to 2018 and extracted needle-syringe distribution coverage data from a recent systematic review. We generated country-, region-, and global-level estimates of daily or more injecting. We also ran meta-regression analyses to determine associations between daily or more injecting and socio-demographic characteristics, injecting risk behaviour, non-fatal overdose, injection site skin infection, and blood borne virus prevalence. RESULTS: Our search resulted in 61,077 sources, from which 198 studies were eligible for inclusion in this review. There were 74 countries with estimates for injecting frequency. Globally, we estimated that 68.1% (95%CI 64.5-71.6%) of PWID, equating to approximately 10.5 (95% UI 6.8-15.0) million people, inject daily or more frequently. There was a higher percentage of participants reporting daily or more injecting among samples with shorter injecting careers, more male participants and higher reporting of opioids as their main drug injected. Daily or more injecting was also associated with samples reporting a higher prevalence of HIV and hepatitis C antibody (anti-HCV), non-fatal overdose, and receptive needle sharing in the previous month. IMPLICATIONS: WHO recently recommended a needle-syringe distribution target of 300 needles per PWID per year which is unlikely to be sufficient for the majority of PWID injecting daily or more who are out of drug treatment. FUNDING: The Australian National Drug and Alcohol Research Centre, Australian National Health and Medical Research Council, University of New South Wales.

Associations between national development indicators and the age profile of people who inject drugs: results from a global systematic review and meta-analysis.

BACKGROUND: Globally, an estimated 15·6 million people inject drugs. We aimed to investigate global variation in the age profile of people who inject drugs (PWID), identify country-level factors associated with age of PWID, and assess the association between injecting drug use (IDU) in young people and rates of injecting and sexual risk behaviours at the country level. METHODS: We derived data from a previously published global systematic review done in April, 2016 (and updated in June, 2017) on the percentage of young PWID, duration of IDU, average age of PWID, average age at IDU initiation, and the percentage of PWID reporting sexual and injecting risk behaviours. We also derived national development indicators from World Bank data. We estimated the percentage of young PWID for each country, using a random-effects meta-analysis (DerSimonian-Laird methodology) and generated pooled regional and global estimates for all indicators of IDU in young people. We used univariable and multivariable generalised linear models to test for associations between the age indicators and country urban population growth, youth unemployment percentage, the percentage of PWID who are female, the percentage of the general population aged 15-24 years, Gini coefficient, opioid substitution therapy coverage (per PWID per year), gross domestic product (GDP) per capita (US$1000), and sexual and injecting risk behaviours. FINDINGS: In the original systematic review, data on age of PWID was reported in 741 studies across 93 countries. Globally, 25·3% (95% uncertainty interval [UI] 19·6-31·8) of PWID were aged 25 years or younger. The highest percentage of young PWID resided in eastern Europe (43·4%, 95% UI 39·4-47·4), and the lowest percentage resided in the Middle East and north Africa (6·9%, 5·1-8·8). At the country level, in multivariable analysis higher GDP was associated with longer median injecting duration (0·11 years per $1000 GDP increase, 95% CI 0·04-0·18; p=0·002), and older median age of PWID (0·13 years per $1000 increase, 0·06-0·20; p<0·0001). Urban population growth was associated with higher age at IDU initiation (1·40 years per annual percentage change, 0·41-2·40). No associations were identified between indicators of IDU in young people and youth unemployment, Gini coefficient, or opioid substitution therapy coverage provision at the country level. No associations were identified between injecting and sexual risk behaviours and age of PWID. INTERPRETATION: Variation in the age profile of PWID was associated with GDP and urbanisation. Regions with the highest prevalence of young PWID (aged ≤25 years) had low coverage of interventions to prevent the spread of blood-borne viruses. Data quality highlights the need for improvements in monitoring of PWID populations. FUNDING: Australian National Drug and Alcohol Research Centre, Australian National Health and Medical Research Council, Open Society Foundation, WHO, the Global Fund, UNAIDS, National Institute for Health Research Health Protection Research Unit for Evaluation of Interventions, Wellcome Trust.

Depression, post-traumatic stress disorder, suicidality and self-harm among people who inject drugs: A systematic review and meta-analysis.

BACKGROUND: A range of negative experiences and circumstances that are common among people who inject drugs (PWID) are risk factors for developing mental disorders. Despite this, there has been no systematic review of the prevalence of mental health indicators among PWID. Thus, we aimed to estimate the prevalence of depression, post-traumatic stress disorder (PTSD), suicidality and self-harm among PWID. METHODS: We searched the peer-reviewed and grey literature for data on depression, PTSD, suicidality and non-suicidal self-harm among PWID from sources published from 2008-2018. We pooled estimates of depression and suicidality using random-effects meta-analysis and provided a narrative summary of estimates of PTSD and self-harm. FINDINGS: We found 23 studies that reported on these mental health indicators among PWID. The pooled estimate for current severe depressive symptomology was 42.0 % (95 % confidence interval [CI] = 21.3, 62.8 %), and for a depression diagnosis was 28.7 % (95 % CI = 20.8, 36.6 %). With much variation, the pooled lifetime prevalence of a suicide attempt was 22.1 % (95 % CI = 19.3, 24.9 %). There were only two studies each that reported on PTSD and non-suicidal self-harm among PWID. INTERPRETATION: Recent data investigating these mental health indicators among PWID was limited, particularly from low- and middle-income countries. Even so, estimates were high and call for further research into the epidemiology of such mental health disorders and self-harming behaviours, as well as the promotion of integrated mental health and substance dependence treatment. Finally, incorporating suicide prevention strategies into services accessed by PWID must be considered as a harm reduction priority.

Modelling the potential prevention benefits of a treat-all hepatitis C treatment strategy at global, regional and country levels: A modelling study.

The World Health Organization (WHO) recently produced guidelines advising a treat-all policy for HCV to encourage widespread treatment scale-up for achieving HCV elimination. We modelled the prevention impact achieved (HCV infections averted [IA]) from initiating this policy compared with treating different subgroups at country, regional and global levels. We assessed what country-level factors affect impact. A dynamic, deterministic HCV transmission model was calibrated to data from global systematic reviews and UN data sets to simulate country-level HCV epidemics with ongoing levels of treatment. For each country, the model projected the prevention impact (in HCV IA per treatment undertaken) of initiating four treatment strategies; either selected randomly (treat-all) or targeted among people who inject drugs (PWID), people aged ≥35, or those with cirrhosis. The IA was assessed over 20 years. Linear regression was used to identify associations between IA per treatment and demographic factors. Eighty-eight countries (85% of the global population) were modelled. Globally, the model estimated 0.35 (95% credibility interval [95%CrI]: 0.16-0.61) IA over 20 years for every randomly allocated treatment, 0.30 (95%CrI: 0.12-0.53) from treating those aged ≥35 and 0.28 (95%CrI: 0.12-0.49) for those with cirrhosis. Globally, treating PWID achieved 1.27 (95%CrI: 0.68-2.04) IA per treatment. The IA per randomly allocated treatment was positively associated with a country's population growth rate and negatively associated with higher HCV prevalence among PWID. In conclusion, appreciable prevention benefits could be achieved from WHO's treat-all strategy, although greater benefits per treatment can be achieved through targeting PWID. Higher impact will be achieved in countries with high population growth.

The prevalence of non-fatal overdose among people who inject drugs: A multi-stage systematic review and meta-analysis.

BACKGROUND: People who inject drugs (PWID) are at an elevated risk of fatal overdose in the first year after experiencing a non-fatal event. Such non-fatal events may also result in overdose-related sequelae, ranging from physical injury to paralysis. Given variation in drug markets and treatment availability across countries and regions, we may see similar variations in non-fatal overdose prevalence. Monitoring non-fatal overdose prevalence among PWID is essential for informing treatment intervention efforts, and thus our review aims to estimate the global, regional, and national prevalence of non-fatal overdose, and determine characteristics associated with experiencing such an event. METHODS: We conducted a systematic review and meta-analyses to estimate country, regional, and global estimates of recent and lifetime non-fatal overdose prevalence among PWID. Using meta-regression analyses we also determined associations between sample characteristics and non-fatal overdose prevalence. RESULTS: An estimated 3.2 (1.8-5.2) million PWID have experienced at least one overdose in the previous year. Among PWID, 20.5% (15.0-26.1%) and 41.5% (34.6-48.4%) had experienced a non-fatal event in the previous 12 months and lifetime respectively. Frequent injecting was strongly associated with PWID reporting recent and lifetime non-fatal overdose. Estimates of recent non-fatal overdose were particularly high in Asia and North America. CONCLUSION: Around one in five PWID are at an elevated risk of fatally overdosing every year, however there is substantial geographical variation. In countries with higher rates of non-fatal overdose there is need to introduce or mainstream overdose prevention strategies such as opioid agonist treatment and naloxone administration training programs.

Prevalence of HIV, HCV and HBV infection and sociodemographic characteristics of people who inject drugs in China: A systematic review and meta-analysis.

BACKGROUND: Globally, China is the largest country by population and contributes substantially to the burden of people who inject drugs (PWID). The aims of this study were to estimate the prevalence of HIV, hepatitis C virus (HCV) and hepatitis B virus (HBV) among PWID at the national and subnational level in China and examine characteristics of PWID. METHODS: We undertook a systematic review of studies published from 2008 to 2017 on HIV, HCV, and HBV seroprevalence among PWID, and characteristics of PWID in Mainland China, Hong Kong, Macao and Taiwan. Meta-analyses were conducted to generate pooled prevalence estimates by province, region, and nationally. RESULTS: Eighty-five papers were included. The pooled HIV, HCV antibody and HBV prevalence among PWID in China was 10.5% (95% confidence interval [95%CI]: 8.6%-12.5%), 71.6% (65.7%-77.6%) and 19.6% (13.7%-25.5%), respectively. In Mainland China, HIV prevalence was highest in the Southwest (14.4%, 10.5%-18.4%) and lowest in the North (1.3%, 0.4%-3.4%). Xinjiang Province had the highest HIV prevalence (42.6%, 35.5%-49.8%). HCV antibody prevalence was highest in the Southwest (77.7%, 69.9%-85.4%), followed by South (76.2%, 65.9%-86.4%). Sichuan had the highest HCV antibody prevalence (91.7%, 86.6%-95.3%), followed by Guangxi (86.1%, 81.8%-90.4%). HBsAg prevalence among PWID was highest in South (25.3%, 14.6%-36.0%), followed by Central (20.8%, 17.4%-24.1%). HBsAg prevalence ranged from 2.4% (0.6-5.9%) in Guizhou to 40.0% (33.7%-46.6%) in Shannxi Province. In China, women and young people accounted for 21.3% and 23.1% of PWID, respectively. It was estimated that 96.1% of PWID injected opioids mainly, and recent injecting risk and sexual risk was reported by 28.5% and 36.7%. CONCLUSION: There is a large burden of HIV, HCV and HBV prevalence among PWID in China, with considerable geographic variation. The disease burden of viral hepatitis is particularly high, implying that effective management should be integrated into harm reduction interventions among PWID in China.

The contribution of injection drug use to hepatitis C virus transmission globally, regionally, and at country level: a modelling study.

BACKGROUND: WHO aims to eliminate the hepatitis C virus (HCV) as a public health threat by 2030. Injection drug use is an important risk factor for HCV transmission, but its contribution to country-level and global epidemics is unknown. We estimated the contribution of injection drug use to risk for HCV epidemics globally, regionally, and at country level. METHODS: We developed a dynamic deterministic HCV transmission model to simulate country-level HCV epidemics among people who inject drugs and the general population. Each country's model was calibrated using country-specific data from UN datasets and systematic reviews on the prevalence of HCV and injection drug use. The population attributable fraction of HCV transmission associated with injection drug use was estimated-defined here as the percentage of HCV infections prevented if additional HCV transmission due to injection drug use was removed between 2018 and 2030. FINDINGS: The model included 88 countries (85% of the global population). The model predicted 0·23% (95% credibility interval [CrI] 0·16-0·31) of the global population were injection drug users in 2017, and 8% (5-12) of prevalent HCV infections were among people who currently inject drugs. Globally, if the increased risk for HCV transmission among people who inject drugs was removed, an estimated 43% (95% CrI 25-67) of incident HCV infections would be prevented from 2018 to 2030, varying regionally. This population attributable fraction was higher in high-income countries (79%, 95% CrI 57-97) than in countries of low and middle income (38%, 24-64) and was associated with the percentage of a country's prevalent HCV infections that are among people who inject drugs. INTERPRETATION: Unsafe injecting practices among people who inject drugs contribute substantially to incident HCV infections globally. Any intervention that can reduce HCV transmission among people who inject drugs will have a pronounced effect on country-level incidence of HCV. FUNDING: None.

A Global Meta-analysis of the Prevalence of HIV, Hepatitis C Virus, and Hepatitis B Virus Among People Who Inject Drugs-Do Gender-Based Differences Vary by Country-Level Indicators?

BACKGROUND: Women-specific factors exist that increases vulnerability to drug-related harms from injection drug use, including blood-borne viruses (BBVs), but gender-based differences in BBV prevalence have not been systematically examined. METHODS: We conducted meta-analyses to estimate country, regional, and global prevalence of serologically confirmed human immunodeficiency virus (HIV), hepatitis C virus (HCV; based on detection of anti-HCV antibody), and hepatitis B virus (HBV; based on detection of HBV surface antigen) in people who inject drugs (PWID), by gender. Gender-based differences in the BBV prevalence (calculated as the risk among women relative to the risk among men) were regressed on country-level prevalence and inequality measures (Gender inequality index, Human development index, Gini coefficient, and high, low or middle income of the country). RESULTS: Gender-based differences varied by countries and regions. HIV prevalence was higher among women than men in sub-Saharan Africa (relative risk [RR], 2.8; 95% confidence interval [CI], 1.8-4.4) and South Asia (RR, 1.7; 95% CI, 1.1-2.7); anti-HCV was lower among women in the Middle East and North Africa (RR, 0.6; 95% CI, .5-.7) and East and Southeast Asia (RR, 0.8; 95% CI, .7-.9). Gender-based differences varied with country-levels of the BBV prevalence in the general population, human development, and income distribution. CONCLUSION: HIV was more prevalent in women who inject drugs as compared to their male counterparts in some countries, but there is variation between and within regions. In countries where women are at higher risks, there is a need to develop gender-sensitive harm-reduction services for the particularly marginalized population of women who inject drugs.

Global, regional, and country-level estimates of hepatitis C infection among people who have recently injected drugs.

BACKGROUND AND AIMS: People who have recently injected drugs are a priority population in efforts to achieve hepatitis C virus (HCV) elimination. This study estimated the prevalence and number of people with recent injecting drug use living with HCV, and the proportion of people with recent injecting drug use among all people living with HCV infection at global, regional and country-levels. METHODS: Data from a global systematic review of injecting drug use and HCV antibody prevalence among people with recent (previous year) injecting drug use were used to estimate the prevalence and number of people with recent injecting drug use living with HCV. These data were combined with a systematic review of global HCV prevalence to estimate the proportion of people with recent injecting drug use among all people living with HCV. RESULTS: There are an estimated 6.1 million [95% uncertainty interval (UI) = 3.4-9.2] people with recent injecting drug use aged 15-64 years living with HCV globally (39.2% viraemic prevalence; UI = 31.6-47.0), with the greatest numbers in East and Southeast Asia (1.5 million, UI = 1.0-2.1), eastern Europe (1.5 million, UI = 0.7-2.4) and North America (1.0 million, UI = 0.4-1.7). People with recent injecting drug use comprise an estimated 8.5% (UI = 4.6-13.1) of all HCV infections globally, with the greatest proportions in North America (30.5%, UI = 11.7-56.7), Latin America (22.0%, UI = 15.3-30.4) and eastern Europe (17.9%, UI = 8.2-30.9). CONCLUSIONS: Although, globally, 39.2% of people with recent injecting drug use are living with hepatitis C virus (HCV) and 8.5% of all HCV infections occur globally among people with recent injecting drug use, there is wide variation among countries and regions.

Global statistics on alcohol, tobacco and illicit drug use: 2017 status report.

AIMS: This review provides an up-to-date curated source of information on alcohol, tobacco and illicit drug use and their associated mortality and burden of disease. Limitations in the data are also discussed, including how these can be addressed in the future. METHODS: Online data sources were identified through expert review. Data were obtained mainly from the World Health Organization, United Nations Office on Drugs and Crime and Institute for Health Metrics and Evaluation. RESULTS: In 2015, the estimated prevalence among the adult population was 18.4% for heavy episodic alcohol use (in the past 30 days); 15.2% for daily tobacco smoking; and 3.8, 0.77, 0.37 and 0.35% for past-year cannabis, amphetamine, opioid and cocaine use, respectively. European regions had the highest prevalence of heavy episodic alcohol use and daily tobacco use. The age-standardized prevalence of alcohol dependence was 843.2 per 100 000 people; for cannabis, opioids, amphetamines and cocaine dependence it was 259.3, 220.4, 86.0 and 52.5 per 100 000 people, respectively. High-income North America region had among the highest rates of cannabis, opioid and cocaine dependence. Attributable disability-adjusted life-years (DALYs) were highest for tobacco smoking (170.9 million DALYs), followed by alcohol (85.0 million) and illicit drugs (27.8 million). Substance-attributable mortality rates were highest for tobacco smoking (110.7 deaths per 100 000 people), followed by alcohol and illicit drugs (33.0 and 6.9 deaths per 100 000 people, respectively). Attributable age-standardized mortality rates and DALYs for alcohol and illicit drugs were highest in eastern Europe; attributable age-standardized tobacco mortality rates and DALYs were highest in Oceania. CONCLUSIONS: In 2015 alcohol use and tobacco smoking use between them cost the human population more than a quarter of a billion disability-adjusted life years, with illicit drugs costing further tens of millions. Europeans suffered proportionately more, but in absolute terms the mortality rate was greatest in low- and middle-income countries with large populations and where the quality of data was more limited. Better standardized and rigorous methods for data collection, collation and reporting are needed to assess more accurately the geographical and temporal trends in substance use and its disease burden.

Pharmaceutical opioid use and harm in Australia: The need for proactive and preventative responses.

There are parallels between the North American experience of escalating pharmaceutical opioid utilisation and harm and the trends being observed in Australia. In Australia, opioid utilisation has increased dramatically over the past two decades. There have been significant shifts away from the predominant prescribing of 'weak' and short-acting opioids, to 'strong' and long-acting opioids, for an increasing range of chronic pain indications. In concordance with escalating use, Australia is experiencing increases in opioid-related hospital admissions and overdose, as well as opioid dependence and treatment seeking. Despite increasing concern regarding pharmaceutical opioid use and harms in Australia, responses have been limited. There have been no recent changes in regulatory systems for prescription-only pharmaceutical opioids, opioid prescribing guidelines, limits on doctors' prescribing, monitoring of patient or doctor access to opioids, or in access to medicines via public subsidy. Potentially abuse-deterrent opioid formulations have entered the Australian market, with studies suggesting that these formulations are less likely to be tampered with by people who inject drugs; but to date, there have been limited impacts on opioid utilisation and harm. Additional strategies may include enhancing access to effective approaches to pain management and opioid dependence, and scaling-up naloxone provision. There is a unique opportunity for a proactive and preventative response to pharmaceutical opioids in Australia, to avoid experiencing the scale of problems seen elsewhere.

Global prevalence of injecting drug use and sociodemographic characteristics and prevalence of HIV, HBV, and HCV in people who inject drugs: a multistage systematic review.

BACKGROUND: Sharing of equipment used for injecting drug use (IDU) is a substantial cause of disease burden and a contributor to blood-borne virus transmission. We did a global multistage systematic review to identify the prevalence of IDU among people aged 15-64 years; sociodemographic characteristics of and risk factors for people who inject drugs (PWID); and the prevalence of HIV, hepatitis C virus (HCV), and hepatitis B virus (HBV) among PWID. METHODS: Consistent with the GATHER and PRISMA guidelines and without language restrictions, we systematically searched peer-reviewed databases (MEDLINE, Embase, and PsycINFO; articles published since 2008, latest searches in June, 2017), searched the grey literature (websites and databases, searches between April and August, 2016), and disseminated data requests to international experts and agencies (requests sent in October, 2016). We searched for data on IDU prevalence, characteristics of PWID, including gender, age, and sociodemographic and risk characteristics, and the prevalence of HIV, HCV, and HBV among PWID. Eligible data on prevalence of IDU, HIV antibody, HBsAg, and HCV antibody among PWID were selected and, where multiple estimates were available, pooled for each country via random effects meta-analysis. So too were eligible data on percentage of PWID who were female; younger than 25 years; recently homeless; ever arrested; ever incarcerated; who had recently engaged in sex work, sexual risk, or injecting risk; and whose main drugs injected were opioids or stimulants. We generated regional and global estimates in line with previous global reviews. FINDINGS: We reviewed 55 671 papers and reports, and extracted data from 1147 eligible records. Evidence of IDU was recorded in 179 of 206 countries or territories, which cover 99% of the population aged 15-64 years, an increase of 31 countries (mostly in sub-Saharan Africa and the Pacific Islands) since a review in 2008. IDU prevalence estimates were identified in 83 countries. We estimate that there are 15·6 million (95% uncertainty interval [UI] 10·2-23·7 million) PWID aged 15-64 years globally, with 3·2 million (1·6-5·1 million) women and 12·5 million (7·5-18·4 million) men. Gender composition varied by location: women were estimated to comprise 30·0% (95% UI 28·5-31·5) of PWID in North America and 33·4% (31·0-35·6) in Australasia, compared with 3·1% (2·1-4·1) in south Asia. Globally, we estimate that 17·8% (10·8-24·8) of PWID are living with HIV, 52·3% (42·4-62·1) are HCV-antibody positive, and 9·0% (5·1-13·2) are HBV surface antigen positive; there is substantial geographic variation in these levels. Globally, we estimate 82·9% (76·6-88·9) of PWID mainly inject opioids and 33·0% (24·3-42·0) mainly inject stimulants. We estimate that 27·9% (20·9-36·8) of PWID globally are younger than 25 years, 21·7% (15·8-27·9) had recently (within the past year) experienced homelessness or unstable housing, and 57·9% (50·5-65·2) had a history of incarceration. INTERPRETATION: We identified evidence of IDU in more countries than in 2008, with the new countries largely consisting of low-income and middle-income countries in Africa. Across all countries, a substantial number of PWID are living with HIV and HCV and are exposed to multiple adverse risk environments that increase health harms. FUNDING: Australian National Drug and Alcohol Research Centre, Australian National Health and Medical Research Council, Open Society Foundation, World Health Organization, the Global Fund, and UNAIDS.

Global, regional, and country-level coverage of interventions to prevent and manage HIV and hepatitis C among people who inject drugs: a systematic review.

BACKGROUND: People who inject drugs (PWID) are a key population affected by the global HIV and hepatitis C virus (HCV) epidemics. HIV and HCV prevention interventions for PWID include needle and syringe programmes (NSP), opioid substitution therapy (OST), HIV counselling and testing, HIV antiretroviral therapy (ART), and condom distribution programmes. We aimed to produce country-level, regional, and global estimates of coverage of NSP, OST, HIV testing, ART, and condom programmes for PWID. METHODS: We completed searches of peer-reviewed (MEDLINE, Embase, and PsycINFO), internet, and grey literature databases, and disseminated data requests via social media and targeted emails to international experts. Programme and survey data on each of the named interventions were collected. Programme data were used to derive country-level estimates of the coverage of interventions in accordance with indicators defined by WHO, UNAIDS, and the UN Office on Drugs and Crime. Regional and global estimates of NSP, OST, and HIV testing coverage were also calculated. The protocol was registered on PROSPERO, number CRD42017056558. FINDINGS: In 2017, of 179 countries with evidence of injecting drug use, some level of NSP services were available in 93 countries, and there were 86 countries with evidence of OST implementation. Data to estimate NSP coverage were available for 57 countries, and for 60 countries to estimate OST coverage. Coverage varied widely between countries, but was most often low according to WHO indicators (<100 needle-syringes distributed per PWID per year; <20 OST recipients per PWID per year). Data on HIV testing were sparser than for NSP and OST, and very few data were available to estimate ART access among PWID living with HIV. Globally, we estimate that there are 33 (uncertainty interval [UI] 21-50) needle-syringes distributed via NSP per PWID annually, and 16 (10-24) OST recipients per 100 PWID. Less than 1% of PWID live in countries with high coverage of both NSP and OST (>200 needle-syringes distributed per PWID and >40 OST recipients per 100 PWID). INTERPRETATION: Coverage of HIV and HCV prevention interventions for PWID remains poor and is likely to be insufficient to effectively prevent HIV and HCV transmission. Scaling up of interventions for PWID remains a crucial priority for halting the HIV and HCV epidemics. FUNDING: Open Society Foundations, The Global Fund, WHO, UNAIDS, United Nations Office on Drugs and Crime, Australian National Drug and Alcohol Research Centre, University of New South Wales Sydney.