Challenges and facilitators in repeated bio-behavioural surveys for blood-borne virus infections in Australian prisons.

BACKGROUND: Prison-based blood-borne virus (BBV) surveillance is essential for evaluation of prevention and treatment programs for high-risk populations, such as people who inject drugs who are over-represented amongst those incarcerated. Regular triennial surveillance has been in place in Australian prisons for almost two decades, but has been focused to date only on new prison entrants. Recently, the Australian Hepatitis and risk survey in prisons (AusHep study) was established to provide improved surveillance via an expanded bio-behavioural survey representative of all people in prison, including those sentenced and those on remand. This paper aims to identify the challenges and facilitators in conducting bio-behavioural surveys for BBV infections in prison settings. METHODS: Randomly selected individuals in 23 prisons, representative of prisons and people in prison (male/female, security classification, rural location, Aboriginal or Torres Strait Islander), were offered point-of-care testing for HIV and hepatitis C (HCV) antibodies, hepatitis B virus surface (HBs) antigen, and HCV RNA (if HCV antibody positive). Data regarding risk behaviours, harm reduction measures, and prior BBV testing and treatment were collected by interview. Data was also collected on the challenges and facilitators encountered during planning and implementation at each participating prison. RESULTS: In the first round, AusHep recruited 1599 participants (98 % participation, 89 % male, median age 35 years, 49 % ever injected drugs). Major implementation challenges included: slow and complex ethics and governance requirements in each jurisdiction, and challenging logistical arrangements and participant access constraints in the prisons. Major facilitators included use of point-of-care testing allowing immediate feedback of results, strong support from jurisdictional stakeholders in correction and public health sectors, flexibility in the timing and detailed planning for each site, and computer tablet-based data collection. CONCLUSION: The high participation and informative findings indicated clear feasibility of this improved surveillance system. Strong stakeholder engagement and flexibility in logistics facilitated successful implementation of multi-jurisdictional prison-based surveillance.

Corrigendum to "Trends in decompensated cirrhosis and hepatocellular carcinoma among people with a hepatitis B notification in New South Wales" [JHEP Reports 4 (2022)].

[This corrects the article DOI: 10.1016/j.jhepr.2022.100552.].

Vaccination coverage among people who inject drugs: A systematic review.

BACKGROUND: People who inject drugs may be at excess risk of acquiring vaccine-preventable diseases and negative associated health outcomes, but experience barriers to vaccination. We aimed to determine vaccination coverage among people who inject drugs globally. METHODOLOGY: We conducted systematic searches of the peer-reviewed and grey literature, date limited from January 2008 to August 2023, focusing on diseases for which people who inject drugs are at elevated risk for and for which an adult vaccination dose is recommended (COVID-19, hepatitis A, hepatitis B, human papillomavirus, influenza, pneumococcal disease, tetanus). To summarise available data, we conducted a narrative synthesis. RESULTS: We included 78 studies/reports comprising 117 estimates of vaccination coverage across 36 countries. Most estimates were obtained from high income countries (80%, n=94). We located estimates for hepatitis B vaccination in 33 countries, which included 18 countries with data on serological evidence of vaccine-derived hepatitis B immunity (range: 6-53%) and 22 countries with self-report data for vaccine uptake (<1-96%). Data for other vaccines were scarcer: reported hepatitis A vaccination coverage ranged 3-89% (five countries), COVID-19 ranged 4-84% (five countries), while we located estimates from fewer than five countries for influenza, tetanus, pneumococcal disease, and human papillomavirus. CONCLUSION: Estimates were sparse but where available indicative of suboptimal vaccination coverage among people who inject drugs. Improving the consistency, timeliness, and geographic coverage of vaccine uptake data among this population is essential to inform efforts to increase uptake.

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.

Scale-up of Direct-Acting Antiviral Treatment in Prisons Is Both Cost-effective and Key to Hepatitis C Virus Elimination.

Background: The Surveillance and Treatment of Prisoners With Hepatitis C (SToP-C) study demonstrated that scaling up of direct-acting antiviral (DAA) treatment reduced hepatitis C virus (HCV) transmission. We evaluated the cost-effectiveness of scaling up HCV treatment in statewide prison services incorporating long-term outcomes across custodial and community settings. Methods: A dynamic model of incarceration and HCV transmission among people who inject drugs (PWID) in New South Wales, Australia, was extended to include former PWID and those with long-term HCV progression. Using Australian costing data, we estimated the cost-effectiveness of scaling up HCV treatment in prisons by 44% (as achieved by the SToP-C study) for 10 years (2021-2030) before reducing to baseline levels, compared to a status quo scenario. The mean incremental cost-effectiveness ratio (ICER) was estimated by comparing the differences in costs and quality-adjusted life-years (QALYs) between the scale-up and status quo scenarios over 40 years (2021-2060) discounted at 5% per annum. Univariate and probabilistic sensitivity analyses were performed. Results: Scaling up HCV treatment in the statewide prison service is projected to be cost-effective with a mean ICER of A$12 968/QALY gained. The base-case scenario gains 275 QALYs over 40 years at a net incremental cost of A$3.6 million. Excluding DAA pharmaceutical costs, the mean ICER is reduced to A$6 054/QALY. At the willingness-to-pay threshold of A$50 000/QALY, 100% of simulations are cost-effective at various discount rates, time horizons, and changes of treatment levels in prison and community. Conclusions: Scaling up HCV testing and treatment in prisons is highly cost-effective and should be considered a priority in the national elimination strategy. Clinical Trials Registration: NCT02064049.

Temporal change in aetiology and clinical characteristics of hepatocellular carcinoma in a large cohort of patients in New South Wales, Australia.

BACKGROUND: Viral hepatitis, alcohol-related liver disease (ARLD) and nonalcoholic fatty liver disease (NAFLD) are the main risk factors for hepatocellular carcinoma (HCC) in many countries. In Australia, given the access to hepatitis C virus (HCV) direct-acting antiviral (DAA) therapy since 2016, a temporal change in HCC aetiology was hypothesized. This study evaluated the temporal change in the aetiology and characteristics of HCC in New South Wales (NSW). METHODS: Patients diagnosed with HCC, admitted to three public hospitals in NSW between 2008 and 2021, were included in the analyses. We assessed the annual frequency of each HCC aetiology and the distribution of HCC characteristics in participants. RESULTS: Among 1370 patients, the most common HCC etiologies were HCV (n = 483, 35%), ARLD (n = 452, 33%), NAFLD (n = 347, 25%) and hepatitis B virus (n = 301, 22%). The proportion of HCV-related HCC was the highest in 2011-2016 (41%) and significantly declined to 30% in 2017-2021 (odds ratio [OR], 0.53 [95% confidence interval (CI), 0.35-0.79]; P = 0.002). The proportion of HCC diagnosed at an early stage (Barcelona Clinic Liver Cancer stage O/A) increased from 41% in 2008-2009 to 56% in 2020-2021 (OR per annum, 1.05 [95% CI, 1.02-1.08]; P = 0.002), and the proportion of patients receiving potentially curative HCC management increased from 29% in 2008-2009 to 41% in 2020-2021 (OR per annum, 1.06 [95% CI, 1.03-1.10]; P < 0.001). CONCLUSION: The contribution of HCV to HCC burden has been decreasing in the DAA era, suggesting the role of HCV elimination in decreasing HCC risk. Increasing frequency of less advanced HCC at diagnosis over time suggests improved HCC surveillance.

Postoperative Outcomes of Intracapsular Tonsillectomy With Coblation: A Systematic Review and Meta-Analysis.

OBJECTIVE: Following tonsillectomy, postoperative pain and hemorrhage from the tonsillar bed are causes of significant morbidity. Intracapsular tonsillectomy with Coblation is suggested to minimize such morbidity while remaining efficacious in long-term outcomes. This systematic review and meta-analysis assessed short-term morbidity and long-term outcomes from intracapsular tonsillectomy with Coblation, focusing primarily on posttonsillectomy hemorrhage. DATA SOURCES: Medline, Embase, and the Cochrane Library. REVIEW METHODS: Guided by PRISMA guidelines, studies on intracapsular tonsillectomy with Coblation published between December 2002 and July 2022 evaluating frequency of posttonsillectomy hemorrhage were screened. Studies without primary data were excluded. Meta-analysis was conducted using the random-effect model. The primary outcome was the proportion of patients who experienced posttonsillectomy hemorrhage. The secondary outcomes were posttonsillectomy pain, the proportion requiring revision tonsillectomy, and severity of sleep-disordered breathing measured by polysomnography outcomes. RESULTS: From 14 studies there were 9821 patients. The proportion of total posttonsillectomy hemorrhage was 1.0% (95% confidence interval [CI] 0.5%-1.6%, n = 9821). The proportion experiencing primary hemorrhage, secondary hemorrhage, and those requiring further tonsil surgery were 0.1% (95% CI 0.0%-0.1%; study n = 7), 0.8% (95% CI 0.2%-1.4%; study n = 7), and 1.4% (95% CI 0.6%-2.2%; study n = 6), respectively. Mean reduction in apnea-hypopnea index was -16.0 events per hour (95% CI -8.8 to -23.3, study n = 3) and mean increase in oxygen nadir was 5.9% (95% CI 2.6%-9.1%, study n = 3). CONCLUSION: Intracapsular tonsillectomy with Coblation has been demonstrated to have a low rate of posttonsillectomy hemorrhage. Data regarding long-term tonsil regrowth and need for reoperation were encouraging of the efficacy of this technique.

Incidence of hepatitis C virus infection in the prison setting: The SToP-C study.

People in prison are at high risk of HCV given high injecting drug use prevalence. This study evaluated HCV incidence and associated injecting drug use characteristics in prison. The SToP-C study enrolled people incarcerated in four Australian prisons. Participants were tested for HCV at enrolment and then every 3-6 months (October-2014 to November-2019). Participants eligible for this analysis included those at-risk of HCV primary infection (anti-HCV negative) or re-infection (anti-HCV positive, HCV RNA negative) with follow-up assessment. A total of 1643 eligible participants were included in analyses (82% male; median age 33 years; 30% injected drugs in prison; 1818 person-years of follow-up). Overall HCV incidence was 6.11/100 person-years (95%CI: 5.07-7.35), with higher rate of re-infection (9.34/100 person-years; 95%CI: 7.15-12.19) than primary infection (4.60/100 person-years; 95%CI: 3.56-5.96). In total population (n = 1643), HCV risk was significantly higher among participants injecting drugs in prison [vs. no injecting; adjusted hazard ratio (aHR): 10.55, 95%CI: 5.88-18.92), and those who were released and re-incarcerated during follow-up (vs. remained incarcerated; aHR: 1.60, 95%CI: 1.03-2.49). Among participants who injected recently (during past month, n = 321), HCV risk was reduced among those receiving high-dosage opioid agonist therapy (OAT), i.e. methadone ≥60 mg/day or buprenorphine ≥16 mg/day, (vs. no OAT, aHR: 0.11, 95%CI: 0.02-0.80) and increased among those sharing needles/syringes without consistent use of disinfectant to clean injecting equipment (vs. no sharing, HR: 4.60, 95%CI: 1.35-15.66). This study demonstrated high HCV transmission risk in prison, particularly among people injecting drugs. High-dosage OAT was protective, but improved OAT coverage and needle/syringe programmes to reduce sharing injecting equipment are required.

Global, regional, and country-level coverage of testing and treatment for HIV and hepatitis C infection among people who inject drugs: a systematic review.

BACKGROUND: People who inject drugs are disproportionately affected by HIV and hepatitis C virus (HCV) infections, while there is little global data on HIV and HCV testing and treatment coverage of this population. We conducted a systematic review to evaluate country-level, regional, and global coverage of HIV and HCV testing and treatment among people who inject drugs. METHODS: We did a systematic review, and searched bibliographic databases (MEDLINE, Embase, and PsycINFO) and grey literature for studies published between Jan 1, 2017, and April 30, 2022, that evaluated the proportion of people who inject drugs who received testing or treatment for HIV or HCV. For each country, we estimated the proportion of people who inject drugs tested for HIV antibodies in the past 12 months (recent), people who inject drugs ever tested for HCV antibodies and HCV RNA, people who inject drugs with HIV currently receiving antiretroviral therapy, and people who inject drugs with HCV ever receiving HCV antiviral treatment. Regional and global estimates, weighted by the population size of people who inject drugs, were generated where sufficient data were available. This study is registered with PROSPERO (CRD42020173974). FINDINGS: 512 documents reported data eligible for analyses, including 337 peer-reviewed articles, 27 conference abstracts or presentations, and 148 documents from grey literature or supplementary searches. Data of recent HIV antibody testing were available for 67 countries and ever having had HCV antibody testing were available for 49 countries. Globally, an estimated 48·8% of people who inject drugs were recently tested for HIV antibodies (95% uncertainty interval [UI] 43·3-54·2%; range 0·9-86·0%), and 47·1% had ever been tested for HCV antibodies (95% UI 43·4-51·0%; range 0·0-93·3%). HCV RNA testing data were available from three countries. Coverage of HIV antibody testing was high (>75%) in four countries and for HCV antibody testing in 15 countries. The estimated uptake of current HIV treatment (18 countries) ranged from 2·6% to 81·9%, and the estimated uptake of ever having HCV treatment (23 countries) ranged from 1·8% to 88·6% across countries. Uptake of HIV treatment was high in two countries, and of HCV treatment in one country. INTERPRETATION: HIV and HCV testing and treatment uptake among people who inject drugs was highly variable, and suboptimal in most countries. Strategies to improve access to HIV and HCV care among people who inject drugs and the availability of public health surveillance are urgently required. FUNDING: Australian National Health and Medical Research Council and UK National Institute for Health and Care Research Health Protection Research Unit in Behavioural Science and Evaluation.

Cascade of care among people with hepatitis B in New South Wales, Australia.

Hepatitis B virus (HBV) care cascade characterisation is important for monitoring HBV elimination progress. This study evaluated care cascade and factors associated with HBV DNA testing and treatment in New South Wales, Australia. HBV care cascade were determined through linkage of HBV notifications (1993-2017) to Medicare and pharmaceutical benefits schemes (2010-2018). Timely HBV DNA testing was within 4 weeks of HBV notification. Multivariate Cox proportional hazards regression evaluated factors associated with HBV DNA testing and treatment. Among 15,202 people with HBV notification, 10,479 (69%) were tested for HBV DNA. A total of 3179 (21%) initiated HBV treatment. HBV DNA testing was more likely among age ≥45 years (adjusted hazard ratio [aHR] 1.07, 95% CI: 1.02, 1.12), hepatocellular carcinoma (HCC) (aHR 1.23, 95% CI: 1.01, 1.50), coinfection (aHR 1.61, 95% CI: 1.23, 2.09), later notification (2014-2017) (aHR 1.21, 95% CI: 1.16, 1.26) and less likely among females (aHR 0.95, 95% CI: 0.91, 0.99), history of alcohol use disorder (AUD) (aHR 0.77, 95% CI: 0.66, 0.89), HCV coinfection (aHR .62, 95% CI: 0.55, 0.70) and Indigenous peoples (aHR 0.84, 95% CI: 0.71, 0.98). HBV treatment was associated with age ≥45 years (aHR 1.35, 95% CI: 1.24, 1.48), decompensated cirrhosis (aHR 2.07, 95% CI: 1.62, 2.65), HCC (aHR 2.96, 95% CI: 2.35, 3.74), HIV coinfection (aHR 4.27, 95% CI: 3.43, 5.31) and later notification (2014-2017) (aHR 1.37, 95% CI: 1.26, 1.47). HBV treatment was less likely among females (aHR 0.68, 95% CI: 0.63, 0.73) and Indigenous peoples (aHR 0.58, 95% CI: 0.42, 0.80). HBV DNA testing and treatment coverage have increased, but remain sub-optimal among some key populations.

Health-related quality of life among people who inject drugs in Australia.

PURPOSE: There is limited research on health-related quality of life (HRQoL) among people who inject drugs (PWID). We aimed to evaluate factors associated with HRQoL among a cohort of PWID in Australia. METHODS: Participants were enrolled in an observational cohort study (the LiveRLife Study) between 2014 and 2018 at 15 sites in Australia. They provided fingerstick whole-blood samples for point-of-care HCV RNA testing and underwent transient elastography to assess liver disease. Participants completed the EQ-5D-3L survey at enrolment. Regression models were used to assess the impact of clinical and socioeconomic characteristics on the EQ-5D-3L scores. RESULTS: Among 751 participants (median age, 43 years; 67% male), 63% reported injection drug use in the past month, 43% had current HCV infection, and 68% had no/mild liver fibrosis (F0/F1). The mean EQ-5D-3L and EQ-VAS scores were 0.67 and 62, respectively, for the overall study population. There was no significant difference in the EQ-5D-3L scores among people with and without recent injecting drug use (mean: 0.66 vs. 0.68, median: 0.73 vs. 0.78, P = 0.405), and among people receiving and not receiving opioid agonist therapy (mean: 0.66 vs. 0.68, median: 0.73 vs. 0.76, P = 0.215). Participants who were employed were found to have the highest mean EQ-5D-3L (0.83) and EQ-VAS scores (77). The presence of current HCV infection, liver fibrosis stage, and high-risk alcohol consumption had little impact on HRQoL. CONCLUSIONS: The study findings provide important HRQoL data for economic evaluations, useful for guiding the allocation of resources for HCV elimination strategies and interventions among PWID.

Factors associated with hepatitis C treatment uptake among females of childbearing age in New South Wales, Australia: A population-based study.

INTRODUCTION: Females of childbearing age with hepatitis C virus (HCV) face increased marginalisation with intersecting, sex-specific barriers to direct acting antiviral (DAA) therapy. We assessed the factors associated with uptake of DAA therapy among females of childbearing age, including those with evidence of recent drug dependence. METHODS: HCV notifications in New South Wales, Australia (1995-2017) were linked to opioid agonist therapy (OAT), hospitalisations, incarcerations, perinatal, HIV notifications, deaths and prescription databases. Recent drug dependence was defined as hospitalisation due to injectable drugs or receipt of OAT occurring in the DAA era (2016-2018). Logistic regression was used to analyse factors associated with DAA uptake among females of childbearing age (18-44), including those with recent drug dependence. RESULTS: Among 57,467 people with evidence of chronic HCV in the DAA era (2016-2018), 20,161 (35%) were female, including 33% (n = 6563/20,161) of childbearing age (18-44). Among all females of childbearing age (n = 6563) and those with evidence of recent drug dependence (n = 2278/6563, 35%), DAA uptake was lower among those who had given birth in the DAA era (vs. no birth record, all females of childbearing age; aOR: 0.74, 95% CI 0.61, 0.89; those with recent drug dependence; aOR 0.69, 95% CI 0.51, 0.93) and Aboriginal and Torres Strait Islander peoples (all females of childbearing age; aOR 0.81, 95% CI 0.71, 0.93; those with recent drug dependence aOR 0.75, 95% CI 0.62, 0.90). CONCLUSION: Females of childbearing age should be considered a key population for DAA therapy. Enhancing antenatal and postnatal HCV care may be critical in the pursuit towards elimination.

Hepatitis C Virus Reinfection in a Real-World Cohort of Homeless-Experienced Individuals in Boston.

BACKGROUND: People experiencing homelessness are disproportionately affected by hepatitis C virus (HCV) infection compared with housed populations. Surveillance for HCV reinfection after successful treatment is a critical step in the care cascade, but limited data on reinfection are available among this highly marginalized group. This study assessed posttreatment reinfection risk in a real-world cohort of homeless-experienced individuals in Boston. METHODS: Individuals receiving HCV direct-acting antiviral treatment through Boston Health Care for the Homeless Program during 2014-2020 with posttreatment follow-up assessment were included. Reinfection was identified based on recurrent HCV RNA at 12 weeks posttreatment with HCV genotype switch or any recurrent HCV RNA following sustain virologic response. RESULTS: A total of 535 individuals were included (81% male, median age 49 years, 70% unstably housed or homeless at treatment initiation). Seventy-four HCV reinfections were detected, including 5 second reinfections. HCV reinfection rate was 12.0/100 person-years (95% confidence interval [CI]: 9.5-15.1) overall, 18.9/100 person-years (95% CI: 13.3-26.7) among individuals with unstable housing and 14.6/100 person-years (95% CI: 10.0-21.3) among those experiencing homelessness. In adjusted analysis, experiencing homelessness (vs stable housing, adjusted hazard ratio, 2.14; 95% CI: 1.09-4.20; P = .026) and drug use within 6 months before treatment (adjusted hazard ratio, 5.23; 95% CI: 2.25-12.13; P < .001) were associated with increased reinfection risk. CONCLUSIONS: We found high HCV reinfection rates in a homeless-experienced population, with increased risk among those homeless at treatment. Tailored strategies to address the individual and systems factors impacting marginalized populations are required to prevent HCV reinfection and to enhance engagement in posttreatment HCV care.

Epidemiology of injecting drug use, prevalence of injecting-related harm, and exposure to behavioural and environmental risks among people who inject drugs: a systematic review.

BACKGROUND: People who inject drugs are exposed to various and changing risk environments and are at risk of multiple harms related to injecting drug use (IDU). We aimed to undertake a global systematic review of the prevalence of IDU, key IDU-related harms (including HIV, hepatitis C virus [HCV], and hepatitis B virus [HBV] infection and overdose), and key sociodemographic characteristics and risk exposures for people who inject drugs. METHODS: We systematically searched for data published between Jan 1, 2017, and March 31, 2022, in databases of peer-reviewed literature (MEDLINE, Embase, and PsycINFO) and grey literature as well as various agency or organisational websites, and disseminated data requests to international experts and agencies. We searched for data on the prevalence, characteristics, and risks of people who inject drugs, including gender, age, sexuality, drug-use patterns, HIV, HCV, and HBV infections, non-fatal overdose, depression, anxiety, and injecting-related disease. Additional data were extracted from studies identified in our previous review. Meta-analyses were used to pool the data where multiple estimates were available for a country. We present country, regional, and global estimates for each variable examined. FINDINGS: We screened 40 427 reports published between 2017 and 2022, and the 871 eligible reports identified were added to the 1147 documents from the previous review. Evidence of IDU was documented in 190 of 207 countries and territories, and 14·8 million people (95% uncertainty interval [UI] 10·0-21·7) aged 15-64 years globally were estimated to inject drugs. Existing evidence suggests that there might be 2·8 million (95% UI 2·4-3·2) women and 12·1 million (95% UI 11·0-13·3) men who inject drugs globally, and that 0·4% (95% CI 0·3-1·3) of people who inject drugs identify as transgender. The amount of available data on key health and social risks among people who inject drugs varied widely across countries and regions. We estimated that 24·8% (95% CI 19·5-31·6) of people who inject drugs globally had experienced recent homelessness or unstable housing, 58·4% (95% CI 52·0-64·8) had a lifetime history of incarceration, and 14·9% (95% CI 8·1-24·3) had recently engaged in sex work, with substantial geographical variation. Injecting and sexual risk behaviour varied considerably geographically, as did risks of harms. Globally, we estimated that 15·2% (95% CI 10·3-20·9) of people who inject drugs are living with HIV, 38·8% (95% CI 31·4-46·9) have current HCV infection, 18·5% (95% CI 13·9-24·1) have recently overdosed, and 31·7% (95% CI 23·6-40·5) have had a recent skin or soft tissue infection. INTERPRETATION: IDU is being identified in a growing number of countries and territories that comprise more than 99% of the global population. IDU-related health harms are common, and people who inject drugs continue to be exposed to multiple adverse risk environments. However, quantification of many of these exposure and harms is inadequate and must be improved to allow for better targeting of harm-reduction interventions for these risks. FUNDING: Australian National Health and Medical Research Council.

Global coverage of interventions to prevent and manage drug-related harms among people who inject drugs: a systematic review.

BACKGROUND: Harm reduction and treatment programmes are essential for reducing harms for people who inject drugs (PWID). We aimed to update estimates from a 2017 review of global coverage of needle and syringe exchange programmes (NSPs), opioid agonist treatment (OAT), and other harm reduction services that target PWID (eg, take-home naloxone [THN] programmes, supervised consumption facilities, and drug checking services). METHODS: We did a systematic review of available evidence from peer-reviewed and grey literature databases for studies published between Jan 1, 2017, and May 31, 2022. Programmatic data were collected on the availability of services, the number of sites, people accessing services, and equipment distributed in countries where there is evidence of injecting drug use. National estimates of coverage of OAT (ie, number of people accessing OAT per 100 PWID) and NSPs (ie, number of needles and syringes distributed per PWID per year) were generated where available using the most recent data. Regional and global estimates were derived and compared with WHO indicators. The study was registered with PROSPERO (CRD42020173974). FINDINGS: We included 195 studies and found there were 90 countries implementing OAT (75% of the PWID population) and 94 countries implementing NSPs (88% of the global PWID population). Only five countries (2% of the global PWID population) are providing high coverage of both services. Far fewer countries were implementing THN programmes (n=43), supervised consumption facilities (n=17), and drug checking services (n=26), with nine countries implementing all five services. Globally, we estimated there were 18 (95% uncertainty interval [UI] 12-27) people accessing OAT per 100 PWID, and 35 (95% UI 24-52) needles and syringes being distributed per person who injects drugs per year. More countries reported high (OAT 24; NSPs 10), moderate (OAT 8; NSPs 15), and low (OAT 38; NSPs 47) coverage of services compared with the previous review. INTERPRETATION: Global coverage of OAT and NSPs has increased modestly in the past 5 years but remains low for most countries. Programmatic data on other key harm reduction interventions are scarce. FUNDING: Australian National Health and Medical Research Council.

Increasing national trend of direct-acting antiviral discontinuation among people treated for HCV 2016-2021.

BACKGROUND: Direct-acting antiviral (DAA) treatment discontinuation may negatively impact HCV elimination efforts. In Australia, DAA therapy is pharmacy dispensed, generally in 4-week amounts, with the approved duration (8-24 wk) and volume dispensed reported in pharmaceutical administrative data. This analysis assessed national HCV treatment discontinuation. METHODS: Individuals commencing DAAs between 2016 and 2021 were assessed for treatment discontinuation. Individuals with a single dispensation of their entire treatment course were excluded. Treatment discontinuation was defined as ≥4 weeks of approved treatment duration not dispensed. Factors associated with treatment discontinuation were assessed using Cox regression. Factors associated with retreatment following treatment discontinuation were assessed using logistic regression. RESULTS: Of 95,275 individuals who were treated, 88,986 were included in the analysis of whom 7532 (9%) discontinued treatment. Treatment discontinuation increased from 6% in the first half of 2016 to 15% in 2021. Longer treatment durations (vs. 8 wk) were associated with increased discontinuation risk (12 wk: adjusted HR = 3.23; 95% CI: 2.90, 3.59; p < 0.001, 16-24 wk: adjusted HR = 6.29; 95% CI: 5.55, 7.14; p < 0.001). Of individuals discontinuing treatment, 24% were retreated. Early discontinuation (4 wk treatment dispensed) increased the likelihood of retreatment (adjusted OR = 3.91; 95% CI: 3.44, 4.44; p < 0.001). Those with early discontinuation of glecaprevir/pibrentasvir 8 weeks (vs. sofosbuvir/velpatasvir 12 wk) had a lower likelihood of retreatment (adjusted OR = 0.62; 95% CI: 0.49, 0.79; p < 0.001). Initial treatment discontinuation was associated with an increased risk of retreatment discontinuation (adjusted HR = 4.41; 3.85, 5.05; p < 0.001). CONCLUSIONS: DAA treatment discontinuation increased over time corresponding to increasing treatment uptake through primary care among people who inject drugs. The use of simplified, short-duration therapies may reduce treatment discontinuation. Access to adherence support and retreatment will be essential for HCV elimination.

Liver-related mortality among people with hepatitis B and C: Evaluation of definitions based on linked healthcare administrative datasets.

Routinely collected and linked healthcare administrative datasets could be used to monitor mortality among people with hepatitis B (HBV) and C (HCV). This study aimed to evaluate the concordance in records of liver-related mortality among people with an HBV or HCV notification, between data on hospitalization for end-stage liver disease (ESLD) and death certificates. In New South Wales, Australia, HBV and HCV notifications (1993-2017) were linked to hospital admissions (2001-2018), all-cause mortality (1993-2018) and cause-specific mortality (1993-2016) datasets. Hospitalization for ESLD was defined as a first-time hospital admission due to decompensated cirrhosis (DC) or hepatocellular carcinoma (HCC). Consistency of liver death definition of mortality following hospitalization for ESLD was compared with two death certificate-based definitions of liver deaths coded among primary and secondary cause-specific mortality data, including ESLD-related (deaths due to DC and HCC) and all-liver deaths (ESLD-related and other liver-related causes). Of 63,292 and 107,430 individuals with an HBV and HCV notification, there were 4478 (2.6%) post-ESLD hospitalization deaths, 5572 (3.3%) death certificate liver disease deaths and 2910 (1.7%) death certificate ESLD deaths. Between 2001 and 2016, among HBV post-ESLD hospitalization deaths (n = 891), 63% (562) had death certificate ESLD recorded, and 83% (741) had death certificate liver disease recorded. Between 2001 and 2016, among HCV post-ESLD hospitalization deaths (n = 3587), 58% (2082) had death certificate ESLD recorded, and 87% (3135) had death certificate liver disease recorded. At least one-third of death certificates with DC and HCC as cause of death had no mention of HBV, HCV or viral hepatitis. Our study identified limitations in estimating and tracking HBV and HCV liver disease mortality using death certificate-based data only. The optimum data for this purpose is either ESLD hospitalisations with vital status information or a combination of these with cause-specific death certificate data.

Patient-Reported Outcomes During and After Hepatitis C Virus Direct-Acting Antiviral Treatment Among People Who Inject Drugs.

OBJECTIVES: People who inject drugs (PWID) are at a high risk of hepatitis C virus (HCV) infection. HCV cure is associated with improved patient-reported outcomes (PROs), but there are little data among PWID. This study aimed to assess the change in PROs during and after HCV direct-acting antiviral (DAA) treatment. METHODS: This analysis used data from 2 clinical trials of DAA treatment in PWID. PROs assessed included health-related quality of life, social functioning, psychological distress, housing, and employment. Generalized estimating equations and group-based trajectory modeling were used to assess changes in PROs over time. RESULTS: No significant changes in the 3-level version of EQ-5D scores, EQ visual analogue scale scores, social functioning, psychological distress, and housing were observed over the 108-week study period. There was a significant increase in the proportion of participants employed (18% [95% confidence interval (CI) 12%-23%] at baseline to 28% [95% CI 19%-36%] at the end of the study). Participants were more likely to be employed at 24 weeks and 108 weeks after commencing treatment. Having stable housing increased the odds of being employed (odds ratio 1.70; 95% CI 1.00-2.90). The group-based trajectory modeling demonstrated that most outcomes remained stable during and after DAA treatment. CONCLUSIONS: Although no significant improvement was identified in health-related quality of life after HCV DAA treatment, there was a modest but significant increase in employment during study follow-up. The study findings support the need for multifaceted models of HCV care for PWID addressing a range of issues beyond HCV treatment to improve quality of life.

Interventions to enhance testing and linkage to treatment for hepatitis C infection for people who inject drugs: A systematic review and meta-analysis.

BACKGROUND: With the advent of direct acting antiviral (DAA) therapies for the treatment of hepatitis C virus (HCV), the World Health Organization recommended a goal to eliminate HCV as a public health threat globally by 2030. With the majority of new and existing infections in high income countries occurring among people who inject drugs, achieving this goal will require the design and implementation of interventions which address the unique barriers to HCV care faced by this population. METHODS: In this systematic review and meta-analysis, we searched bibliographic databases and conference abstracts to July 21, 2020 for studies assessing interventions to improve the following study outcomes: HCV antibody testing, HCV RNA testing, linkage to care, and treatment initiation. We included both randomised and non-randomised studies which included a comparator arm. We excluded studies which enrolled only paediatric populations (<18 years old) and studies where the intervention was conducted in a different healthcare setting than the control or comparator. This analysis was restricted to studies conducted among people who inject drugs. Data were extracted from the identified records and meta-analysis was used to pool the effect of interventions on study outcomes. This study was registered in PROSPERO (CRD42020178035). FINDINGS: Of 15,342 unique records, 45 studies described the implementation of an intervention to improve HCV testing, linkage to care and treatment initiation among people who inject drugs. These included 27 randomised trials and 18 non-randomised studies with the risk of bias rated as "critical" for most non-randomised studies. Patient education and patient navigation to address patient-level barriers to HCV care were shown to improve antibody testing uptake and linkage to HCV care respectively although patient education did not improve antibody testing when restricted to randomised studies. Provider care coordination to address provider level barriers to HCV care was effective at improving antibody testing uptake. Three different interventions to address systems-level barriers to HCV care were effective across different stages of HCV care: point-of-care antibody testing (linkage to care); dried blood-spot testing (antibody testing uptake); and integrated care (linkage to care and treatment initiation). INTERPRETATION: Multiple interventions are available that can address the barriers to HCV care for people who inject drugs at the patient-, provider-, and systems-level. The design of models of care to improve HCV testing and treatment among people who inject drugs must consider the unique barriers to care that this population faces. Further research, including high-quality randomised controlled trials, are needed to robustly assess the impact these interventions can have in varied populations and settings.