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BackgroundWhile opioid agonist therapy (OAT) reduces the risk of hepatitis C virus (HCV) acquisition among people who inject drugs (PWID), protective effects may be attenuated in females. We used pooled data from an international collaboration of prospective cohorts to assess sex disparities in HCV incidence among PWID exposed to OAT.MethodsIndependent predictors of HCV infection were identified using Cox regression models with random effects after accounting for the clustering effect of study sites. Unadjusted and adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) are presented in sex-specific analyses.ResultsAmong 701 participants exposed to OAT, HCV incidence was 16.5/100 person-years of observation (PYO) (95% CI, 13.1-20.7) in females and 7.6/100 PYO (95% CI, 6.0-9.5) in males (female:male adjusted HR [aHR], 1.80 [95% CI, 1.37-2.22]; P < .001). Factors associated with HCV acquisition among females exposed to OAT included nonwhite race (aHR, 1.79 [95% CI, 1.25-2.56]; P = .001), unstable housing (aHR, 4.00 [95% CI, 3.62-4.41]; P < .001), daily or more frequent injection (aHR, 1.45 [95% CI, 1.01-2.08]; P = .042), and receptive syringe sharing (aHR, 1.43 [95% CI, 1.33-1.53]; P < .001).ConclusionsFemale PWID exposed to OAT are twice as likely as their male counterparts to acquire HCV. While there is a need for better understanding of sex differences in immune function and opioid pharmacokinetic and pharmacodynamic parameters, structural and behavioral interventions that target women are required to bolster the efficacy of OAT in preventing HCV transmission.

Background and Aims: Hepatitis C virus (HCV) burden is higher among people in prison given high prevalence of injecting drug use. This study evaluated direct‐acting antiviral (DAA) treatment outcome in prisons. Methods: The Surveillance and Treatment of Prisoners with hepatitis C (SToP‐C) study enrolled individuals incarcerated in four Australian prisons (2017–2019). Participants with detectable HCV RNA were offered sofosbuvir‐velpatasvir for 12 weeks. Sustained virological response (SVR) was assessed in intention‐to‐treat (ITT; participants commencing treatment and due for SVR assessment before study close) and per‐protocol (PP; participants with documented treatment completion and SVR assessment) populations. Results: Among 799 participants with HCV, 324 (41%) commenced treatment (94% male; median age, 32 years; median duration of incarceration, 9 months). In ITT population (n = 310), 201 had documented treatment completion (65% [95% CI: 59–70]), and 137 achieved SVR (ITT‐SVR: 44% [95% CI: 39–50]). In PP population (n = 143), 137 achieved SVR (PP‐SVR: 96% [95% CI: 91–98]). Six participants had quantifiable HCV RNA at SVR assessment from treatment failure (n = 2) or reinfection (n = 4). Release or inter‐prison transfer was common reasons for no documented treatment completion (n = 106/109 [97%]) and no SVR assessment (n = 57/58 [98%]). In ITT analysis, longer incarceration was associated with increased SVR (adjusted OR per month 1.03 [95% CI: 1.01–1.04]). Conclusion: Among participants who completed DAA treatment and were assessed for SVR, treatment outcome was consistent with non‐prison clinical studies. However, most individuals did not complete treatment or lacked study‐documented treatment outcome due to release or transfer. Strategies to accommodate dynamic prisoner populations are required to ensure continuity of HCV care, including treatment completion and post‐treatment care. [ABSTRACT FROM AUTHOR]

Background:The objective of this study was to assess differences in hepatitis C virus (HCV) incidence by sex in people who inject drugs (PWID), using a large international multicohort set of pooled biological and behavioral data from prospective observational studies of incident human immunodeficiency virus (HIV) and HCV infections in high-risk cohorts (the InC3 Collaborative). Methods:HCV infection date was estimated based on a hierarchy of successive serological (anti-HCV), virological (HCV RNA), and clinical (symptoms and/or liver function tests) data. We used a Cox proportional hazards model to calculate the crude and adjusted female to male (F:M) hazard ratio (HR) for HCV incidence using biological sex as the main exposure. Results:A total of 1868 PWID were observed over 3994 person-years of observation (PYO). Unadjusted F:M HR was 1.38 (95% confidence interval [CI], 1.15-1.65) and remained significant after adjusting for behavioral and demographic risk factors (1.39 [95% CI, 1.12-1.72]). Although syringe and equipment sharing were associated with the highest HCV incidence rate in women (41.62 and 36.83 PYO, respectively), we found no sex differences attributed to these risk factors. Conclusions:Our findings indicate that women who inject drugs may be at greater risk of HCV acquisition than men, independent of demographic characteristics and risk behaviors. Multiple factors, including biological (hormonal), social network, and differential access to prevention services, may contribute to increased HCV susceptibility in women who inject drugs.

BackgroundWe determined temporal trends (1985-2011) in hepatitis C virus (HCV) incidence and associated behavioral exposures for people who inject drugs (PWID) from the United States (Boston, Baltimore, and San Francisco), Canada (Montreal), the Netherlands (Amsterdam), and Australia (Sydney and Melbourne).MethodsUsing population-based cohort data from HCV-negative PWID, we calculated overall and within-city HCV incidence trends, HCV rates by study enrollment period (1985-2011), and temporal trends in exposure behaviors. Poisson regression models estimated trends in HCV incidence over calendar-time. Survival models identified risk factors for HCV incidence across cities and estimated independent effects of city and calendar period on HCV infection risk.ResultsAmong 1391 initially HCV-negative participants followed prospectively (1644.5 person-years of observation [PYO]), 371 HCV incident infections resulted in an overall incidence of 22.6 per 100 PYO (95% confidence interval [CI], 20.4-25.0). Incidence was highest and remained elevated in Baltimore (32.6/100 PYO), San Francisco (24.7/100 PYO), and Montreal (23.5/100 PYO), lowest in Melbourne and Amsterdam (7.5/100 PYO and 13.1/100 PYO, respectively), and moderate (21.4/100 PYO) in Sydney. Higher rates of syringe and equipment sharing and lower prevalence of opioid agonist therapy were associated with HCV incidence in cities with the highest incidence. Risk for infection dropped by 18% for every 3-year increase in calendar-time (adjusted hazard ratio, 0.8 [95% CI, .8-.9]) in the multivariable model.ConclusionsDifferences in prevention strategies and injecting contexts may explain the ongoing high HCV incidence in these North American cities and emphasize the need for scale-up of opioid agonist therapy and increased coverage of needle and syringe programs in North America.

Background & Aims: People who inject drugs (PWID) experience high incarceration rates which are associated with increased hepatitis C virus (HCV) transmission risk. We assess the importance of prison‐based interventions for achieving HCV elimination among PWID in New South Wales (NSW), Australia. Methods: A model of incarceration and HCV transmission among PWID was calibrated in a Bayesian framework to epidemiological and incarceration data from NSW, incorporating elevated HCV acquisition risk among recently released PWID. We projected the contribution of differences in transmission risk during/following incarceration to HCV transmission over 2020–2029. We estimated the past and potential future impact of prison‐based opioid agonist therapy (OAT; ~33% coverage) and HCV treatment (1500 treatments in 2019 with 32.9%–83.3% among PWID) on HCV transmission. We estimated the time until HCV incidence reduces by 80% (WHO elimination target) compared to 2016 levels with or without prison‐based interventions. Results: Over 2020–2029, incarceration will contribute 23.0% (17.9–30.5) of new HCV infections. If prison‐based interventions had not been implemented since 2010, HCV incidence in 2020 would have been 29.7% (95% credibility interval: 22.4–36.1) higher. If current prison and community HCV treatment rates continue, there is an 98.8% probability that elimination targets will be achieved by 2030, with this decreasing to 10.1% without current prison‐based interventions. Conclusions: Existing prison‐based interventions in NSW are critical components of strategies to reduce HCV incidence among PWID. Prison‐based interventions are likely to be pivotal for achieving HCV elimination targets among PWID by 2030. [ABSTRACT FROM AUTHOR]

Introduction: Globally, hepatitis B virus (HBV) is a leading cause of liver disease. People who inject drugs (PWID) are at greater risk than the general population of contracting HBV. This risk could depend on societal factors in different countries. We investigated the associations between country‐level chronic HBV prevalence in PWID with national indicators of development and prevalence of HIV and hepatitis C virus (HCV). Methods: We used global systematic review data on chronic HBV prevalence (hepatitis B surface antigen‐positive) among PWID and country‐level sociodemographic characteristics from online databases. National random‐effects meta‐analysis estimates of HBV prevalence were the outcome in linear regression models testing for associations with country‐level characteristics. Results: The study included 131,710 PWID from 304 estimates in 55 countries: the pooled HBV prevalence among PWID in the countries analysed was 4.5% (95% CI 3.9–5.1), the highest regional pooled prevalence was in East and Southeast Asia (17.6% [13.3–22.3]), and the lowest was in Western Europe (1.7% [1.4–2.1]). In multivariable models, no indicators of development were associated with HBV prevalence, but there was evidence of positive associations between HBV prevalence in the general population and among PWID, and evidence of HIV and HCV prevalence in PWID being associated with HBV prevalence in PWID: multivariable coefficients 0.03 (95% CI 0.01–0.04); p < 0.001, and 0.01 (95% CI 0.00–0.03); p = 0.01, respectively. Discussion and Conclusions: HBV prevalence among PWID was associated with HIV and HCV prevalence among PWID and background HBV prevalence in the general population, highlighting the need for improving harm reduction in PWID and implementation of HBV vaccination, especially where HBV is endemic. [ABSTRACT FROM AUTHOR]

Background Evaluating progress towards hepatitis C virus (HCV) elimination is critical. This study estimated prevalence of current HCV infection and HCV treatment uptake among people who inject drugs (PWID) in Australia. Methods The Enhancing Treatment of Hepatitis C in Opioid Substitution Settings Engage is an observational study of PWID attending drug treatment clinics and needle and syringe programs (NSPs). Participants completed a questionnaire including self-reported treatment history and underwent point-of-care HCV RNA testing (Xpert HCV Viral Load Fingerstick; Cepheid). Results Between May 2018 and September 2019, 1443 participants were enrolled (64% injected drugs in the last month, 74% receiving opioid agonist therapy [OAT]). HCV infection status was uninfected (28%), spontaneous clearance (16%), treatment-induced clearance (32%), and current infection (24%). Current HCV was more likely among people who were homeless (adjusted odds ratio, 1.47; 95% confidence interval, 1.00–2.16), incarcerated in the previous year (2.04; 1.38–3.02), and those injecting drugs daily or more (2.26; 1.43–2.42). Among those with previous chronic or current HCV, 66% (n = 520/788) reported HCV treatment. In adjusted analysis, HCV treatment was lower among females (.68;.48–.95), participants who were homeless (.59;.38–.96), and those injecting daily or more (.51;.31–.89). People aged ≥45 years (1.46; 1.06–2.01) and people receiving OAT (2.62; 1.52–4.51) were more likely to report HCV treatment. Conclusions Unrestricted direct-acting antiviral therapy access in Australia has yielded high treatment uptake among PWID attending drug treatment and NSPs, with a marked decline in HCV prevalence. To achieve elimination, PWID with greater marginalization may require additional support and tailored strategies to enhance treatment. [ABSTRACT FROM AUTHOR]

The aim of this analysis was to evaluate perceived barriers related to HCV testing, management and treatment among physicians practicing in clinics offering opioid agonist treatment (OAT). C‐SCOPE was a study consisting of a self‐administered survey among physicians practicing at clinics providing OAT in Australia, Canada, Europe and the United States between April and May 2017. A 5‐point Likert scale (1 = not a barrier, 3 = moderate barrier, 5 = extreme barrier) was used to measure responses to perceived barriers for HCV testing, evaluation and treatment across the domains of the health system, clinic and patient. Among the 203 physicians enrolled (40% USA, 45% Europe, 14% Australia/Canada), 21% were addiction medicine specialists, 29% psychiatrists and 69% were metro/urban. OAT physicians in this study reported poor access to on‐site venepuncture (35%), point‐of‐care HCV testing (16%), and noninvasive liver disease assessment (25%). Only 30% of OAT physicians reported personally treating HCV infection. Major perceived health system barriers to HCV management included the lack of funding for noninvasive liver disease testing, long wait times to see an HCV specialist, lack of funding for new HCV therapies, and reimbursement restrictions based on drug/alcohol use. Major perceived clinic barriers included the lack of peer support programmes and/or HCV case managers to facilitate linkage to care, the need to refer people off‐site for noninvasive liver disease staging, the lack of support for on‐site phlebotomy and the lack of on‐site delivery of HCV therapy. This study highlights several important modifiable barriers to enhance HCV testing, evaluation and treatment among PWID attending OAT clinics. [ABSTRACT FROM AUTHOR]

Background: International guidelines recommend treatment of hepatitis C virus (HCV) infection in people who inject drugs (PWID), including those on opioid substitution therapy (OST). The pangenotypic combination of glecaprevir and pibrentasvir has shown high sustained virologic response at post-treatment Week 12 (SVR12) in clinical trials. Herein, we evaluate the safety and efficacy of glecaprevir/pibrentasvir in patients receiving OST.Methods: Pooled data from patients with HCV genotypes 1-6 who were treated with glecaprevir/pibrentasvir for 8, 12, or 16 weeks in eight Phase 2 and 3 trials were categorized by use of OST. Treatment completion, treatment adherence, SVR12, adverse events (AEs), and laboratory abnormalities were evaluated for patients receiving and not receiving OST.Results: Among 2256 patients, 157 (7%) were receiving OST. Compared with patients not receiving OST, OST patients were younger (mean age, 46.8 vs 52.8 years), male (69% vs 54%), white (93% vs 80%), HCV treatment-naïve (86% vs 72%), had HCV genotype 3 (60% vs 26%), and had a history of depression or bipolar disorder (43% vs 19%). Most patients completed (OST: 98% [n/N = 154/157]; non-OST: 99% [n/N = 2070/2099]) and were adherent (received ≥90% of study drug doses) to glecaprevir/pibrentasvir treatment (OST: 98% [n/N = 121/123]; non-OST: 99% [n/N = 1884/1905] among patients with available data). In the intention-to-treat population, SVR12 rates in OST and non-OST patients were 96.2% (n/N = 151/157; 95% CI 93.2-99.2) and 97.9% (n/N = 2055/2099; 95% CI 97.3-98.5), respectively. For OST patients, reasons for nonresponse included virologic relapse (<1%; n = 1), premature study drug discontinuation (<1%; n = 1), and loss to follow-up (3%; n = 4). AEs occurring in ≥10% of OST patients were headache, fatigue, and nausea. Drug-related serious AEs, AEs leading to study drug discontinuation, and Grade 3 or higher laboratory abnormalities were infrequent in both groups (<1%). No HCV reinfections occurred through post-treatment Week 12.Conclusion: Glecaprevir/pibrentasvir is highly efficacious and well tolerated in HCV-infected patients receiving OST. [ABSTRACT FROM AUTHOR]

Background: This study evaluated competency related to HCV testing, management and treatment among physicians practicing in clinics offering opioid agonist treatment (OAT).Methods: C-SCOPE is a study consisting of a self-administered survey among physicians practicing at clinics providing OAT in Australia, Canada, Europe and USA between April-May 2017. A 7-point scale was used to measure < average competence (score >4 of 7) related to HCV testing, management and treatment.Results: Among 203 physicians (40% USA, 45% Europe, 14% Australia/Canada) 21% were addiction medicine specialists, 29% psychiatrists, and 70% were metro/urban [mean PWID managed, 51; years of experience, 11]. The majority perceived HCV testing (82%) and treatment (85%) among PWID as important. The minority reported < average competence with respect to regular screening (12%) and interpretation of HCV test results (14%), while greater proportions reported < average competence in advising patients about new HCV therapies (28%), knowledge of new treatments (37%), and treatment/management of HCV (40%). In adjusted analysis, factors independently associated with < average self-reported competency related to the ability to treat HCV and manage side effects included fewer years in medical practice, fewer numbers of patients treated for HCV infection in the past six months, not having obtained information on screening, diagnosing or treatment of HCV, not having attended any training on HCV in the past year, and not having read or consulted AASLD/IDSA, EASL or other guidelines for HCV.Conclusion: Physicians treating HCV infection among PWID attending OAT clinics recognized the importance of HCV testing and treatment. However, self-perceived competency related to HCV management and treatment was low, highlighting the importance of improved HCV education and training among physicians practicing in clinics offering OAT. [ABSTRACT FROM AUTHOR]

The burden of hepatitis C infection is considerable among people who inject drugs (PWID), with an estimated prevalence of 39%, representing an estimated 6.1 million people who have recently injected drugs living with hepatitis C infection. As such, PWID are a priority population for enhancing prevention, testing, linkage to care, treatment and follow‐up care in order to meet World Health Organization (WHO) hepatitis C elimination goals by 2030. There are many barriers to enhancing hepatitis C prevention and care among PWID including poor global coverage of harm reduction services, restrictive drug policies and criminalization of drug use, poor access to health services, low hepatitis C testing, linkage to care and treatment, restrictions for accessing DAA therapy, and the lack of national strategies and government investment to support WHO elimination goals. On 5 September 2017, the International Network of Hepatitis in Substance Users (INHSU) held a roundtable panel of international experts to discuss remaining challenges and future priorities for action from a health systems perspective. The WHO health systems framework comprises six core components: service delivery, health workforce, health information systems, medical procurement, health systems financing, and leadership and governance. Communication has been proposed as a seventh key element which promotes the central role of affected community engagement. This review paper presents recommended strategies for eliminating hepatitis C as a major public health threat among PWID and outlines future priorities for action within a health systems framework. [ABSTRACT FROM AUTHOR]

An editorial is presented which examines the authors' views about a variation in global statistics regarding the prevalence of injecting (intravenous) and opioid drug abuse, and it mentions how some studies use alternative information sources and give value to unreferened country estimates. The 2017 World Drug Report and a Global Burden of Disease (GBD) study are examined, along with cocaine and methamphetamine abuse.

Background: Injecting drug use is associated with considerable morbidity and mortality. Estimates of the size of the population of people who inject drugs are critical to inform service planning and estimate disease burden due to injecting drug use. We aimed to estimate the size of the population of people who inject drugs in Australia.Methods: We applied a multiplier method which used benchmark data (number of people in opioid substitution therapy (OST) on a snapshot day in 2014) and multiplied it by a factor derived from the prevalence of current OST among people who inject drugs participating in the Australian Needle and Syringe Program Survey in 2014. Estimates of the total population of people who inject drugs were calculated in each state and territory and summed to produce a national estimate. We used the sex and age group distribution seen in datasets relating to people who inject drugs to derive sex- and age-stratified estimates, and calculated prevalence per 1000 population.Results: Between 68,000 and 118,000 people aged 15-64 years inject drugs in Australia. The population prevalence of injecting drug use was 6.0 (lower and upper uncertainty intervals of 4.3 and 7.6) per 1000 people aged 15-64 years. Injecting drug use was more common among men than women, and most common among those aged 35-44 years. Comparison of expected drug-related deaths based on these estimates to actual deaths suggest that these figures may be underestimates.Conclusions: These are the first indirect prevalence estimates of injecting drug use in Australia in over a decade. This work has identified that there are limited data available to inform estimates of this population. These estimates can be used as a basis for further work estimating injecting drug use in Australia. [ABSTRACT FROM AUTHOR]

Objective: The aims of this study were to assess symptoms of depression, anxiety, and stress and associated sociodemographic factors among people living with chronic hepatitis C virus (HCV) infection with a history of injecting drug use and to assess the association between symptoms of depression, anxiety, or stress and HCV treatment intent, specialist assessment, or treatment uptake. Methods: The Enhancing Treatment for Hepatitis C in Opioid Substitution Settings was an observational cohort study evaluating the provision of HCV assessment and treatment among people with chronic HCV and a history of injecting drug use, recruited from 9 community health centers and opioid substitution therapy (OST) clinics (New South Wales, Australia). Symptoms were assessed using the Depression Anxiety Stress Scales (DASS-21). Analyses were performed using logistic regression. Results: Among 415 participants (mean age 41 years, 71% male), 47%, 52%, and 36% demonstrated moderate to extremely severe symptoms of depression, anxiety, and stress, respectively. In adjusted analyses, depression symptoms were associated with recent injecting drug use [adjusted odds ratio (aOR) 1.63, 95% confidence interval (CI) 1.07-2.49), whereas stress symptoms were associated with unemployment (aOR 2.99, 95% CI 1.09-8.15) and not living with a spouse or other relatives/friends (aOR 1.55, 95% CI 1.01-2.39). Symptoms of depression, anxiety, or stress or having a history of treated mental illness were not independently associated with HCV treatment intent, specialist assessment, or treatment uptake. Conclusions: Findings suggest a need for improved interventions and care regarding mental health among people living with chronic HCV with a history of injecting drug use, but suggest that symptoms of depression, anxiety, and stress should not be immediate contra-indications to HCV assessment and treatment. [ABSTRACT FROM AUTHOR]

Aims To estimate adherence and response to therapy for chronic hepatitis C virus (HCV) infection among people with a history of injecting drug use. A secondary aim was to identify predictors of HCV treatment response. Design Prospective cohort recruited between 2009 and 2012. Participants were treated with peg-interferon alfa-2a/ribavirin for 24 (genotypes 2/3, G2/3) or 48 weeks (genotype 1, G1). Setting Six opioid substitution treatment (OST) clinics, two community health centres and one Aboriginal community-controlled health organization providing drug treatment services in New South Wales, Australia. Participants Among 415 people with a history of injecting drug use and chronic HCV assessed by a nurse, 101 were assessed for treatment outcomes (21% female). Measurements Study outcomes were treatment adherence and sustained virological response (SVR, undetectable HCV RNA >24 weeks post-treatment). Findings Among 101 treated, 37% ( n = 37) had recently injected drugs (past 6 months) and 62% ( n = 63) were receiving OST. Adherence ≥ 80% was 86% ( n = 87). SVR was 74% (75 of 101), with no difference observed by sex (males: 76%, females: 67%, P = 0.662). In adjusted analysis, age < 35 (versus ≥ 45 years) [adjusted odds ratio (aOR) = 5.06, 95% confidence interval (CI) = 1.47, 17.40] and on-treatment adherence ≥ 80% independently predicted SVR (aOR = 19.41, 95% CI = 3.61, 104.26]. Recent injecting drug use at baseline was not associated with SVR. Conclusions People with a history of injecting drug use and chronic hepatitis C virus attending opioid substitution treatment and community health clinics can achieve adherence and responses to interferon-based therapy similar to other populations, despite injecting drugs at baseline. Younger age and adherence are predictive of improved response to hepatitis C virus therapy. [ABSTRACT FROM AUTHOR]

There is considerable interest in determining the impact that increased uptake of treatment for hepatitis C virus (HCV) infection will have on the burden of HCV among people who inject drugs (PWID). An understanding of the size of the population of PWID, rates of injecting cessation and HCV prevalence and incidence within the PWID population is essential for such exercises. However, these parameters are often uncertain. In this paper we review methods for estimating the size of the population of PWID and related parameters, taking into account the uncertainty that exists around data on the natural history of injecting drug use; consider issues in the estimation of HCV prevalence among PWID; and consider the importance of opioid substitution therapy and prisons as settings for the prevention and treatment of HCV infection among PWID. These latter two points are illustrated through examples of ongoing work in England, Scotland and Australia. We conclude that an improved understanding of the size of PWID populations, including current and former PWID and parameters related to injecting drug use and settings where PWID may be reached, is necessary to inform HCV prevention and treatment strategies. [ABSTRACT FROM AUTHOR]

Background Strategies are needed to enhance screening of hepatitis C virus (HCV) infection among people who inject drugs to improve engagement in HCV treatment, and stem the growing burden of HCV-related morbidity and mortality. Methods We linked routinely collected data on enrolment in opioid substitution therapy (OST) and HCV notifications. We calculated rates of incident HCV notifications, and compared rates in and out of OST. Results Following adjustment for sex, age and calendar period, rates of incident HCV notification were significantly higher during periods of OST, compared to periods out of OST (adjusted incident rate ratio: 1.91; 95% confidence interval: 1.86, 1.97). This effect was seen across multiple treatment periods. Conclusions HCV screening in OST settings increases detection of HCV infection among people who inject drugs. [ABSTRACT FROM AUTHOR]

Background & Aims Despite advances in HCV treatment, recent data on treatment uptake is sparse. HCV treatment uptake and associated factors were evaluated in a community-based cohort in Vancouver, Canada. Methods The CHASE study is a cohort of inner city residents recruited from January 2003-June 2004. HCV status and treatment were retrospectively and prospectively determined through data linkages with provincial virology and pharmacy databases. Logistic regression analyses were used to identify factors associated with HCV treatment uptake. Results Among 2913, HCV antibody testing was performed in 2405, 64% were HCV antibody-positive ( n = 1533). Individuals with spontaneous clearance (18%, n = 276) were excluded. Among the remaining 1257 HCV antibody-positive participants (mean age 42, 71% male), 29% were Aboriginal. At enrolment, the majority reported recent injecting (60%) and non-injecting drug use (87%). Between January 1998 and March 2010, 6% (77 of 1257) initiated HCV treatment. In adjusted analyses, Aboriginal ethnicity [adjusted odds ratio ( AOR) 0.23; 95% CI 0.10, 0.51] and crack cocaine use ( AOR 0.61; 95% CI 0.37, 0.99) were associated with a decreased odds of receiving HCV treatment, while methamphetamine injecting ( AOR 0.16; 95% CI 0.02, 1.18) trended towards a lower odds of receiving treatment. HCV treatment uptake ranged from 0.2 (95% CI 0.0, 0.7) per 100 person-years ( PYs) in 2003 to 1.6 (95% CI 0.9, 2.6) per 100 PYs in 2009. Conclusion HCV treatment uptake remains low in this large community-based cohort of inner city residents with a high HCV prevalence and access to universal healthcare. [ABSTRACT FROM AUTHOR]

Introduction: Over the last two decades, the incidence of hepatitis C virus (HCV) co‐infection among men who have sex with men (MSM) living with HIV began increasing in post‐industrialized countries. Little is known about transmission of acute or recent HCV, in particular among MSM living with HIV co‐infection, which creates uncertainty about potential for reinfection after HCV treatment. Using phylogenetic methods, clinical, epidemiological and molecular data can be combined to better understand transmission patterns. These insights may help identify strategies to reduce reinfection risk, enhancing effectiveness of HCV treatment as prevention strategies. The aim of this study was to identify multi‐risk profiles and factors associated with phylogenetic pairs and clusters among people with recent HCV infection. Methods: Data and specimens from five studies of recent HCV in Australia and New Zealand (2004 to 2015) were used. HCV Core‐E2 sequences were used to infer maximum likelihood trees. Clusters were identified using 90% bootstrap and 5% genetic distance threshold. Multivariate logistic regression and latent class analyses were performed. Results: Among 237 participants with Core‐E2 sequences, 47% were in a pair/cluster. Among HIV/HCV co‐infected participants, 60% (74/123) were in a pair/cluster, compared to 30% (34/114) with HCV mono‐infection (p < 0.001). HIV/HCV co‐infection (vs. HCV mono‐infection; adjusted odds ratio (AOR), 2.37, 95% confidence interval (CI), 1.45, 5.15) was independently associated with phylogenetic clustering. Latent class analysis identified three distinct risk profiles: (1) people who inject drugs, (2) HIV‐positive gay and bisexual men (GBM) with low probability of injecting drug use (IDU) and (3) GBM with IDU & sexual risk behaviour. Class 2 (vs. Class 1, AOR 3.40; 95% CI, 1.52, 7.60), was independently associated with phylogenetic clustering. Many clusters displayed homogeneous characteristics, such as containing individuals exclusively from one city, individuals all with HIV/HCV co‐infection or individuals sharing the same route of acquisition of HCV. Conclusions: Clusters containing individuals with specific characteristics suggest that HCV transmission occurs through discrete networks, particularly among HIV/HCV co‐infected individuals. The greater proportion of clustering found among HIV/HCV co‐infected participants highlights the need to provide broad direct‐acting antiviral access encouraging rapid uptake in this population and ongoing monitoring of the phylogeny. [ABSTRACT FROM AUTHOR]

• Vaccination coverage estimates for people who inject drugs were limited. • Estimates were often outdated and reliant upon self-report. • Data were unavailable for low-income countries and scarce for middle-income countries. • The majority of estimates pertained to hepatitis B vaccination. • Where available, data were indicative of suboptimal vaccine coverage. 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. 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. 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. 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. [ABSTRACT FROM AUTHOR]

There is limited research on health-related quality of life (HRQoL) among people who inject drugs (PWID). We evaluated the HRQoL and associated factors among a cohort of PWID in Australia. Participants were enrolled in an observational cohort study (the Enhancing Treatment of Hepatitis C in Opioid Substitution Settings Engage Study) from May 2018 to September 2019 (wave 1) and November 2019 to June 2021 (wave 2). Participants completed the EQ-5D-5L survey at enrolment. Two-part models were used to assess the association of clinical and socioeconomic characteristics with EQ-5D-5L scores. Among 2395 participants (median age, 43 years; 66% male), 65% reported injecting drug use in the past month, 20% had current hepatitis C virus (HCV) infection, and 68% had no/mild liver fibrosis (F0/F1). Overall, the mean EQ-5D-5L and EQ-visual analog scale scores were 0.78 and 57, respectively. In adjusted analysis, factors associated with significantly lower EQ-5D-5L scores include older ages, female (marginal effect = −0.03, P =.014), being homeless (marginal effect = −0.04, P =.040), and polysubstance use (marginal effect = −0.05, P <.001). Factors associated with significantly higher EQ-5D-5L scores were being Aboriginal/Torres Strait Islander (marginal effect = 0.03, P =.021) and recent injecting drug use in the past 12 months. Current HCV infection and liver fibrosis stage were not associated with reduced HRQoL among the study participants. PWID experienced a lower HRQoL compared with the general population. Further research is needed to understand HRQoL in this population to facilitate the development of multifaceted care models for PWID beyond HCV cure and inform health economic analyses for identifying optimal health strategies for PWID. • There is limited research on health-related quality of life (HRQoL) among people who inject drugs (PWID). Previous studies reporting health utility scores for PWID have been limited by either small sample sizes or the lack of health utility information stratified by important subgroups, such as hepatitis C virus (HCV) infection status and liver disease staging. • PWID in this study experienced a lower HRQoL compared with the general population. Factors associated with lower EQ-5D-5L scores included older ages, being female, being homeless and polysubstance use. However, EQ-5D-5L could not discriminate between participants with different stages of liver disease, nor between participants with and without HCV infection. • This study has provided health utility scores among PWID to inform health economic analyses for identifying optimal health strategies to enhance HCV elimination and improve health outcomes among this population. Further research is needed to validate the use of EQ-5D-5L among PWID and understand factors associated with lower HRQoL. [ABSTRACT FROM AUTHOR]

Prisons are key venues for scaling-up hepatitis C virus (HCV) testing and treatment. Complex clinical pathways and frequent movements of people in prison remain barriers to HCV care. This study evaluated the impact of a 'one-stop-shop' point-of-care HCV RNA testing intervention on treatment uptake compared with standard of care among people recently incarcerated in Australia. PIVOT was a prospective, non-concurrent, controlled study comparing HCV treatment uptake during 'standard of care' (n = 239; November 2019–May 2020) and a 'one-stop-shop' intervention (n = 301; June 2020–April 2021) in one reception prison in Australia. The primary endpoint was uptake of direct-acting antiviral treatment at 12 weeks from enrolment. Secondary outcomes included the time taken from enrolment to each stage in the care cascade. A total of 540 male participants were enrolled. Median age (29 vs. 28 years) and history of injecting drug use (48% vs. 42%) were similar between standard of care and intervention phases. Among people diagnosed with current HCV infection (n = 18/63 in the standard of care phase vs. n = 30/298 in the intervention phase), the proportion initiating direct-acting antiviral treatment within 12 weeks from enrolment in the intervention phase was higher (93% [95% CI 0.78–0.99] vs. 22% [95% CI 0.64–0.48]; p <0.001), and the median time to treatment initiation was shorter (6 days [IQR 5–7] vs. 99 days [IQR 57–127]; p <0.001) compared to standard of care. The 'one-stop-shop' intervention enhanced treatment uptake and reduced time to treatment initiation among people recently incarcerated in Australia, thereby overcoming key barriers to treatment scale-up in the prison sector. This study provides important insights for policymakers regarding optimal HCV testing and treatment pathways for people newly incarcerated in prisons. The findings will improve health outcomes in people in prison with chronic HCV infection by increasing testing and treatment, thereby reducing infections, liver-related morbidity/mortality, and comorbidities. The findings will change clinical practice, clinical guidelines, and international guidance, and will inform future research and national and regional strategies, in particular regarding point-of-care testing, which is being rapidly scaled-up in various settings globally. The economic impact will likely include health budget savings resulting from reduced negative health outcomes relating to HCV, and health system efficiencies resulting from the introduction of simplified models of care. This study is registered at Clinicaltrials.gov (NCT04809246). [Display omitted] • The proportion tested for HCV was higher in the intervention (99%) compared with the control phase (26%). • The proportion treated for HCV was higher in the intervention (93%) compared with the control phase (22%). • Median time from diagnosis to treatment initiation was shorter in the intervention than in the control phase (6 vs. 25 days). • Combining all key HCV assessments into a single visit improved efficiencies and enhanced testing and treatment uptake. [ABSTRACT FROM AUTHOR]

Introduction Methods Results Discussion and Conclusions Evaluating progress towards hepatitis C virus (HCV) elimination among Aboriginal and Torres Strait Islander peoples is critical given the disproportionate burden of infection. We examined factors associated with current HCV infection and self‐reported treatment among Aboriginal and Torres Strait Islander (hereafter referred to as Aboriginal peoples) and non‐Aboriginal peoples who inject drugs (PWID) in Australia.ETHOS Engage is an observational cohort study of PWID attending drug treatment and needle and syringe programs in Australia. Participants underwent point‐of‐care HCV RNA testing (Xpert HCV RNA Viral Load Fingerstick) and completed a questionnaire including self‐reported history of HCV treatment.Between May 2018 and June 2021, 2395 participants were enrolled and 555 (23%) identified as Aboriginal (median age 42 years, 58% were men, 63% injected drugs in last month, 76% ever incarcerated). HCV RNA prevalence was 23% among Aboriginal PWID (24% in 2018–2019 and 21% in 2019–2021; p = 0.44), and 21% among non‐Aboriginal PWID (24% in 2018–2019 and 16% in 2019–2021; p < 0.001). Self‐reported HCV treatment was 65% among Aboriginal PWID (63% in 2018–2019 and 69% in 2019–2021; p = 0.30), and 70% among non‐Aboriginal PWID (67% in 2018–2019 and 75% in 2019–2021; p < 0.001). Among Aboriginal PWID, current HCV infection was associated with recently injecting drugs and receiving opioid agonist treatment, and self‐reported HCV treatment was negatively associated with younger age, homelessness and recently injecting drugs.Equitable access to HCV care and prevention is needed to ensure Australia meets its elimination targets among Aboriginal PWID. [ABSTRACT FROM AUTHOR]

Background. This study investigated the efficacy and safety of directly observed pegylated interferon (peg-IFN) alfa-2a plus self-administered ribavirin (RBV) for the treatment of hepatitis C virus (HCV) among people with active drug use.Methods. A randomized, open-label, parallel group trial of immediate vs delayed treatment with peg-IFN alfa-2a plus RBV in participants with recent injection drug and/or crack cocaine use (prior 3 months). The primary end point was sustained virologic response (SVR).Results. Sixty-six participants were randomized (immediate treatment, n = 48; delayed treatment, n = 18). Loss to follow-up was comparable among those randomized to immediate and delayed treatment (23% vs 33%, P = .389). In a post hoc intent-to-treat analysis of all randomized individuals, the SVR was 65% (95% confidence interval [CI], 49%–78%; 31/48) in those randomized to immediate treatment as compared to 39% (95% CI, 17%–64%; 7/18) in those randomized to delayed treatment (P = .060). Among those who received delayed treatment (12/18), SVR was 58% (7/12). Among 60 participants who received at least 1 dose of study medication, SVR was 63% (95% CI, 50%–75%, n = 38). Recent drug use at baseline (past month) did not impact completion or SVR. Discontinuation due to adverse events occurred in 7%. The HCV reinfection rate was 2.8 per 100 person-years (95% CI, 0.0–14.5 person-years) with 1 reinfection observed among 23 remaining in follow-up post-SVR (median, 1.8 years; range, 0.5–1.8 years).Conclusions. Among people actively using drugs treated with directly observed peg-IFN alfa-2a plus self-administered RBV, SVR is comparable to that seen in clinical trials of non–drug users, and the rate of HCV reinfection is low.Clinical Trials Registration. NCT00203606. [ABSTRACT FROM AUTHOR]

Background. Although guidelines recommend that people who inject drugs (PWID) should not be excluded from hepatitis C (HCV) treatment, some services remain reluctant to treat PWID. The aim of this review was to investigate sustained virologic response (SVR), adherence, discontinuation, and HCV reinfection among PWID.Methods. A search of Medline, Embase, and Cochrane databases (between 2002 and January 2012) was conducted for primary articles/conference abstracts examining HCV treatment outcomes in PWID. Meta-analysis was used to obtain pooled estimates of SVR, adherence, discontinuation, and HCV reinfection.Results. Ten primary articles and 1 conference abstract met the inclusion criteria. Across 6 studies (comprising 314 drug users, of whom 141 [45%] were PWID), pooled SVR was 56% (95% confidence interval [CI], 50%–61%) for all genotypes, 37% (95% CI, 26%–48%) for genotypes 1/4, and 67% (95% CI, 56%–78%) for genotypes 2/3. Pooled 80/80/80 adherence was 82% (95% CI, 74%–89%) across 2 studies, and pooled treatment discontinuation was 22% (95% CI, 16%–27%) across 4 studies. Across 5 studies (comprising 131 drug users) examining reinfection, pooled risk was 2.4 (95% CI, .9–6.1) per 100 person-years.Conclusions. HCV treatment outcomes are acceptable in PWID, supporting treatment guidelines. The pooled estimate of HCV reinfection risk was low, but there was considerable uncertainty around this estimate. Further studies on the risk of reinfection are needed to assess the long-term effectiveness of HCV treatment in PWID. [ABSTRACT FROM AUTHOR]

Background: Among people who inject drugs (PWID), the prevalence of hepatitis C virus (HCV) infection is high; however HCV treatment uptake remains low. New models of care are needed to address the growing burden of HCV-related disease in PWID and to understand the barriers to assessment and treatment of HCV. This study evaluated assessment and treatment for HCV infection among PWID attending an opioid substitution treatment (OST) clinic with an integrated peer support worker model.Methods: Clients with a history of IDU and chronic HCV infection, attending the Newcastle Pharmacotherapy Service, Newcastle Australia, were recruited as part of a multisite prospective observational study (the ETHOS Cohort). Additional chart review was conducted for clients not enrolled in the ETHOS Cohort. A peer support worker was introduced to complement and extend services offered by the clinical team. Client contacts and assessments with a nurse and/or peer worker were evaluated, including those who commenced HCV treatment.Results: A total of 1447 clients attended the OST service during February 2009 and June 2014. Of these, 378 (26%) were assessed by a nurse and 242 (17%) by a clinician. HCV treatment was commenced by 20 (5%) participants and 15 (75%) achieved a sustained virological response (SVR). During May 2009 and July 2011, 332 nurse contacts and 726 peer worker contacts were evaluated. The nurse-led contacts were related to HCV treatment (50%) and review of pathology tests (34%), whereas peer worker contacts included discussion about HCV treatment (75%), education, counselling and/or support (53%) and general discussion about HCV infection (59%).Conclusion: These data demonstrate that peer support workers facilitate broader discussion about HCV treatment, education and/or support, allowing nurses to focus on HCV-related assessment and treatment. HCV treatment uptake was very low in this cohort, but SVR was high. The integration of peer support workers in treatment programs within OST clinics may address barriers to HCV care, but further studies are needed to assess their impact on assessment and treatment outcomes. [ABSTRACT FROM AUTHOR]

Hepatitis C virus (HCV) is a significant concern within prison populations. Provision of HCV testing and treatment for people in prison is expanding and a key component of global elimination efforts. Despite growing service availability, several challenges remain in HCV testing and treatment engagement during incarceration. The PIVOT study demonstrated that a 'one-stop-shop' intervention (point-of-care HCV RNA testing, Fibroscan®, nurse-led clinical assessment, and fast-tracked direct-acting antiviral prescription) enhanced HCV testing and treatment at a reception prison in Australia. Utilising Squier et al's Health Literacy Skills Framework, this analysis aimed to understand HCV health literacy and educational needs among people at a reception prison in Australia. Semi-structured interviews were conducted with twenty-four male PIVOT study participants. Purposive sampling ensured comparable representation of those with: 1) prior HCV testing history (standard pathology / no prior testing), and 2) injecting drug use history (IDU; ever / never). Varied HCV health literacy levels and educational needs were evident amongst people in prison. Whilst those with multiple incarceration episodes and IDU history (prior knowledge) appeared to have stronger HCV health literacy than those without, substantial gaps in HCV health literacy were evident. Knowledge of HCV transmission risks in prison was high, and most understood the importance of HCV testing and treatment in prison (comprehension) , but ability to engage with HCV testing and treatment services, participation in safe injecting behaviours (health-related behaviours) , and knowledge of re-infection and re-treatment, within the context of the prison environment, were suboptimal. There was a general desire for increased HCV education in prison. Gaps in HCV health literacy among people in prison were evident, indicating opportunities for improvement. A targeted HCV education program for people in prison, addressing the gaps identified in this analysis, may enhance HCV testing, treatment, and prevention by fostering stronger HCV health literacy among people in prison. [ABSTRACT FROM AUTHOR]

Women who inject drugs are significantly less likely to initiate hepatitis C virus (HCV) treatment than men. Concerted efforts are needed to minimise gender-based inequalities in care. The study aim was to use a stigma and time framework to investigate how women who inject drugs experienced HCV care in healthcare settings. Semi-structured, in-depth interviews were conducted with 34 participants from the ETHOS Engage Cohort (n = 1,443) in Australia. Inclusion criteria were aged ≥18 years, history of injection drug use, and persons who injected in the prior six months or were currently receiving opioid agonist treatment. Drawing on the original qualitative dataset (n = 34), we conducted a secondary analysis focused on women participants' experiences of receiving HCV related care (n = 21/34). Utilising thematic analysis, we applied Earnshaw's theoretical framework, which incorporates time into stigma and health research via three "timescales" – historical context, human development , and status course. Among the 21 women interviewed (mean age 42 years, 5 are Aboriginal, 11 received HCV treatment), the majority were currently receiving opioid agonist treatment and over half injected drugs in the past month. For historical context , most participants were diagnosed with HCV during the interferon era (1990s-2014). Participants had to navigate a sociomedical landscape not only largely bereft of adequate HCV medical knowledge, appropriate support, and adequate treatments, but were also generally assessed as "unsuitable" for treatment based on their perceived personhood as people who inject drugs. For human development , many participants reported encountering overlapping stigmatizing experiences (layered stigma) while receiving their HCV diagnosis in prenatal care and early postpartum. Under status course , participants acutely recognised the intersection of HCV infection, injection drug use, and gender, and reported concerns about being judged more harshly from healthcare providers as a result. A stigma and time framework illuminated multiple overlapping stigmatizing experiences for women who inject drugs in HCV care and in turn, can help to inform tools and interventions to counter their impact. [ABSTRACT FROM AUTHOR]

• Limited research on non-injecting and licit drug use among people who inject drugs. • Diversity in types of drugs and routes of administration used in this population globally. • Licit drug use commonly reported; tobacco was the most widely used drug overall. • Need for increased availability of non-injection harm reduction interventions. A better understanding of global patterns of drug use among people who inject drugs can inform interventions to reduce harms related to different use profiles. This review aimed to comprehensively present the geographical variation in drug consumption patterns among this population. Systematic searches of peer reviewed (PsycINFO, Medline, Embase) and grey literature published from 2008–2022 were conducted. Data on recent (past year) and lifetime drug use among people who inject drugs were included. Data were extracted on use of heroin, amphetamines, cocaine, benzodiazepines, cannabis, alcohol, and tobacco; where possible, estimates were disaggregated by route of administration (injecting, non-injecting, smoking). National estimates were generated and, where possible, regional, and global estimates were derived through meta-analysis. Of 40,427 studies screened, 394 were included from 81 countries. Globally, an estimated 78.1 % (95 %CI:70.2–84.2) and 71.8 % (65.7–77.2) of people who inject drugs had recently used (via any route) and injected heroin, while an estimated 52.8 % (47.0–59.0) and 19.8 % (13.8–26.5) had recently used and injected amphetamines, respectively. Over 90 % reported recent tobacco use (93.5 % [90.8–95.3]) and recent alcohol use was 59.1 % (52.6–65.6). In Australasia recent heroin use was lowest (49.4 % [46.8–52.1]) while recent amphetamine injecting (64.0 % [60.8–67.1]) and recent use of cannabis (72.3 % [69.9–74.6]) were higher than in all other regions. Recent heroin use (86.1 % [78.3–91.4]) and non–injecting amphetamine use (43.3 % [38.4–48.3]) were highest in East and Southeast Asia. Recent amphetamine use (75.8 % [72.7–78.8]) and injecting heroin use (84.8 % (81.4–87.8) were highest in North America while non–injecting heroin use was highest in Western Europe (45.0 % [41.3–48.7]). There is considerable variation in types of drugs and routes of administration used among people who inject drugs. This variation needs to be considered in national and global treatment and harm reduction interventions to target the specific behaviours and harms associated with these regional profiles of use. [ABSTRACT FROM AUTHOR]

Abstract: Background: A systematic review was conducted to determine whether behavioural interventions are effective in preventing transmission of hepatitis C virus (HCV) amongst people who inject drugs. Methods: Medline, EMBASE, the Cochrane Clinical Trial Database, PSYCHINFO and hand-searching of bibliographies were used to identify controlled trials of behavioural interventions for reducing HCV transmission amongst people who inject drugs. Behavioural interventions were defined as non-pharmacological interventions that aimed to change individual behaviours without explicitly attempting to change population norms. Results: Six trials evaluating peer-education training and counselling interventions were included in the review. There was considerable variation between trials with respect to intervention duration, control and study population. Trials evaluated the impact of interventions on HCV incidence (three studies, 1041 participants) and frequency of injecting risk behaviours (six studies, 2472 participants). Amongst the three studies which measured the impact of the intervention on HCV incidence, none found a statistically significant difference between intervention and control groups. Measures of frequency of injecting risk behaviours varied greatly and could not be pooled. Only two studies (n =418, 854) showed significantly greater reductions in injecting risk behaviours in the intervention group compared with the control group. Conclusions: There was considerable variation in study design, outcome measures and magnitude, direction and statistical significance of findings between studies. Nonetheless, it is unlikely that behavioural interventions can have a considerable effect on HCV transmission. It is likely that multi-component interventions are required. [Copyright &y& Elsevier]

Background: Understanding factors associated with engagement across the hepatitis C virus (HCV) cascade of care (CoC) among people who inject drugs (PWID) is critical for developing targeted interventions to enhance engagement and further HCV elimination efforts. We describe the CoC among Australian PWID, and identify factors associated with engagement at each stage.Methods: As part of the 2018 and 2019 Illicit Drug Reporting System, Australians who regularly inject drugs reported lifetime HCV antibody and RNA testing, treatment uptake and completion. Multivariable logistic regression identified characteristics associated with outcomes.Results: Of 1499 participants, 87% reported antibody testing. Of those, 70% reported RNA testing, of whom 60% reported being RNA positive. Among those, 76% reported initiating treatment, 78% of whom completed. Incarceration history (adjusted odds ratio 1.90; 95% confidence interval 1.28-2.82), current opioid agonist treatment (OAT) (1.99; 1.14-3.47), and recent alcohol and other drug (AOD) counselling (2.22; 1.27-3.88) were associated with antibody testing. Incarceration history (1.42; 1.07-1.87), and current OAT (2.07; 1.51-2.86) were associated with RNA testing. Current OAT (1.92; 1.22-3.03) and recent AOD counselling (1.91; 1.16-3.13) were associated with treatment uptake. Methamphetamine as drug injected most often in the last month was associated with reduced odds of antibody (0.41; 0.25-0.66) and RNA testing (0.54; 0.40-0.74), compared to heroin.Conclusion: CoC engagement amongst Australian PWID is encouraging, with AOD service engagement associated with testing and treatment. Further efforts to reach those not service engaged, particularly those not receiving OAT or who predominantly inject methamphetamine, are needed to achieve HCV elimination targets. [ABSTRACT FROM AUTHOR]

• Women who inject drugs face gendered barriers to care that impact on engagement with HCV services. • Compared to men, women who inject drugs had similar HCV testing, but lower treatment uptake. • Among women, those aged <45 had lower HCV testing and treatment, and higher HCV prevalence. • Women aged <45 need enhanced, gender-informed support to increase HCV testing and treatment. Evaluating gender-specific trends in hepatitis C virus (HCV) treatment uptake among men and women who inject drugs is crucial for ensuring equitable progress towards HCV elimination. This study aimed to quantify differences in testing, treatment, and current HCV infection between men and women who inject drugs. ETHOS Engage is an observational cohort study of people who inject drugs attending drug treatment clinics and needle and syringe programs in Australia recruited from May 2018-September 2019 (wave 1) and November 2019-April 2021 (wave 2). Participants completed a questionnaire including self-reported HCV testing and treatment history and underwent point-of-care HCV RNA testing (Xpert® HCV Viral Load Fingerstick). Logistic regression was used to compare the factors associated with self-reported HCV testing and treatment and current HCV infection for men and women who inject drugs. Among 2,395 participants enrolled in ETHOS Engage, 66% (n = 1,591) were men, 33% (n = 786) women, and <1% (n = 18) did not identify as a man or woman. HCV testing history and current infection were similar among men and women. Among men or women ever eligible for HCV treatment (ever chronic HCV) (n = 1,242), women were less likely to report a history of HCV treatment compared to men (227/352, 64% vs. 631/890, 71%; p = 0.03). Among women, those aged <45 were less likely to report HCV testing (aOR: 0.57, 95%CI: 0.36, 0.90), treatment (aOR: 0.47, 95%CI: 0.29, 0.77), and more likely to have HCV infection (aOR: 1.48, 95%CI: 1.00, 2.20) Among women, those of childbearing age (<45) were less likely to report testing and treatment and were more likely to have current HCV infection. Women <45 years old should be a priority population for HCV care. Services that interface with these women should be optimised to enhance HCV testing and treatment. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Background: Globally, HCV testing, linkage to care and treatment is sub-optimal among people who use drugs (PWUD). This study aimed to evaluate the impact of an innovative intervention to enhance HCV testing, linkage to care, and treatment initiation among PWUD in Tehran, Iran.Methods: ENHANCE is a non-randomized trial evaluating the effect of on-site rapid HCV antibody testing, venepuncture for HCV RNA testing (HCV antibody positive only), liver fibrosis assessment, and linkage to care to enhance direct-acting antiviral (DAA) therapy (sofosbuvir/daclatasvir) initiation for HCV among people with a history of drug use. Recruitment was from April 2018 and will continue to July 2019, through three opioid substitution treatment (OST) clinics, five community-based drop-in centres, and one homeless reception centre. Participants initiated DAA therapy at a specialist clinic (OST clinics) or on-site (other sites), with monitoring provided on-site or at the specialist clinic (for those with cirrhosis attending OST clinics).Results: Among 632 participants enrolled (median age, 44 years), 97% were male, 28% had a history of injecting drug use, and 58% had used drugs within the previous year. HCV antibody prevalence was 27%; 62% and 15% among those with and without a history of injecting drug use. Among 170 HCV antibody positive participants, 168 had HCV RNA testing (99%), of whom 134 (80%) were positive. Among HCV RNA positive participants, treatment initiation was 84%: 100% (45/45), 96% (46/48) and 54% (22/41) in OST clinics, drop-in centres, and homeless reception settings, respectively.Conclusion: Following on-site HCV testing and linkage to care, HCV treatment uptake was extremely high among PWUD, apart from the homeless reception population. This intervention could be explored in other settings globally to enhance HCV scale-up and elimination efforts. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Transfer of hepatitis C virus (HCV) infection from a donor to a new recipient is associated with a bottleneck of genetic diversity in the transmitted viral variants. Existing data suggests that one, or very few, variants emerge from this bottleneck to establish the infection (transmitted founder [T/F] variants). In HCV, very few T/F variants have been characterized due to the challenges of obtaining early infection samples and of high throughput viral genome sequencing. This study used a large, acute HCV, deep-sequenced dataset from first viremia samples collected in nine prospective cohorts across four countries, to estimate the prevalence of single T/F viruses, and to identify host and virus-related factors associated with infections initiated by a single T/F variant. The short reads generated by Illumina sequencing were used to reconstruct viral haplotypes with two haplotype reconstruction algorithms. The haplotypes were examined for random mutations (Poisson distribution) and a star-like phylogeny to identify T/F viruses. The findings were cross-validated by haplotype reconstructions across three regions of the genome (Core-E2, NS3, NS5A) to minimize the possibility of spurious overestimation of single T/F variants. Of 190 acute infection samples examined, 54 were very early acute infections (HCV antibody negative, RNA positive), and single transmitted founders were identified in 14 (26%, 95% CI: 16–39%) after cross validation across multiple regions of the genome with two haplotype reconstruction algorithms. The presence of a single T/F virus was not associated with any host or virus-related factors, notably viral genotype or spontaneous clearance. In conclusion, approximately one in four new HCV infections originates from a single T/F virus. Resolution of genomic sequences of single T/F variants is the first step in exploring unique properties of these variants in the infection of host hepatocytes. • Approximately one in four new HCV infections originates from a single T/F virus • When identifying T/F viruses require haplotype reconstruction, various algorithms may disagree with each other • Cross validation across multiple algorithms will reduce the risk of overestimation of T/F viruses • Phenotypic characterization of T/F variants in HCV is a priority for vaccine design [ABSTRACT FROM AUTHOR]

Highlights • Aptima HCV detects HCV from dried blood spots with good sensitivity/specificity. • Dried blood spots are a suitable alternative to plasma for HCV RNA detection. • Dried blood spots could simplify and enhance HCV testing in people who inject drugs. Abstract Background The availability of effective direct-acting antiviral therapy for hepatitis C virus (HCV) has led to a need for simplified diagnostic pathways. Barriers to treatment uptake, specifically in people who inject drugs and in remote and resource limited settings, may be overcome by utilizing novel collection methods, such as dried blood spots (DBS). However, there are currently no registered assays for HCV RNA testing from DBS samples. Objectives To evaluate the sensitivity and specificity of the Aptima HCV Dx Quant assay for HCV RNA detection in DBS samples Study design 107 paired venepuncture and DBS samples from HCV antibody positive individuals were analyzed for HCV RNA on the Aptima HCV Dx Quant and Roche CAP/CTM (gold standard) HCV assays. Results 78% (n=83) had detectable HCV RNA in plasma. Sensitivity of the Aptima assay for HCV RNA detection in DBS was 96.4% (95% CI 89.8–99.3%) and specificity was 95.8% (95% CI 78.8–99.9%). Sensitivity for HCV RNA detection in DBS using a quantitative threshold of ≥15 IU/mL in plasma was 95.1% (95% CI 88%–98.7%) and specificity was 96.0% (95% CI 79.7%–99.9%). The sensitivity of HCV RNA detection in DBS using a quantitative threshold of ≥1000 IU/mL (based on a clinically relevant threshold) was 100% (95% CI 95.3–100%) and specificity was 100% (95% CI 88.4–100%). Conclusions Our data indicates that the Aptima HCV Dx Quant can detect active HCV infection from a DBS sample with good sensitivity and specificity, particularly when using a threshold of ≥1000 IU/mL. [ABSTRACT FROM AUTHOR]

Graphical abstract Highlights • Evidence to support feasibility of elimination of hepatitis C as a public health threat. • High uptake of hepatitis C treatment reflected in reduction in viraemic prevalence. • Surveillance and monitoring are required to track progress toward elimination goals. Background & Aims The World Health Organization (WHO) established targets to eliminate hepatitis C virus (HCV) infection as a public health threat by 2030. Evidence that HCV treatment can lower viraemic prevalence among people who inject drugs (PWID) is limited. Broad accessibility of direct-acting antiviral (DAA) therapy in Australia, since March 2016, provides an opportunity to assess the efficacy of these treatments at a population level in a real-world setting. Methods Data from Australia's annual bio-behavioural surveillance examined treatment uptake and estimated viraemic prevalence among PWID attending needle syringe programs nationally between 2015 and 2017. Multivariate logistic regression identified variables independently associated with HCV treatment among those considered eligible (anti-HCV positive excluding HCV RNA negative with no self-reported history of HCV treatment) in 2017. Results Annual samples ranged from 1,995–2,380 PWID. Anti-HCV prevalence declined from 57% (2015) to 49% (2017, χ2 p trend <0.001), with 40–56% of anti-HCV positive respondents providing sufficient sample for HCV RNA testing. Between 2015 and 2017, treatment uptake among those eligible increased from 10% to 41% (χ2 p trend <0.001) and viraemic prevalence among the overall sample declined from 43% to 25% (χ2 p trend <0.001). In multivariable analysis, older age (≥50 years adjusted odds ratio [aOR] 1.82; 95% CI 1.09–3.06; p = 0.023 and 44–49 years aOR 1.75; 95% CI 1.03–3.00; p = 0.038 vs. ≤37 years) and history of opioid substitution therapy (aOR 2.06; 95% CI 1.30–3.26; p = 0.002) were independently associated with treatment. Conclusions This study confirms PWID are willing to initiate treatment when HCV DAA therapy is available and provides population-level evidence of a decline in viraemic prevalence among people most at risk of ongoing HCV transmission. Scaled up surveillance and monitoring are required to evaluate progress toward WHO HCV elimination goals. Lay summary The World Health Organization's goal to reduce hepatitis C virus incidence by 80% will be difficult to achieve without widespread scale up and a corresponding reduction in viraemic prevalence among those most at risk of onward transmission. Our results indicate that a population-level reduction in viraemic prevalence is achievable through high levels of treatment and cure among people who inject drugs. [ABSTRACT FROM AUTHOR]

Background: The risk of hepatitis C virus (HCV) reinfection due to continued injecting risk behaviours might remain a barrier to HCV treatment among people who inject drugs. We aimed to evaluate changes in risk behaviours during and following HCV treatment among people with ongoing injecting drug use or receiving opioid substitution treatment (OST).Methods: ACTIVATE was an international multicentre clinical trial conducted between 2012 and 2014. Participants with HCV genotypes 2/3 infection were treated with peg-interferon/ribavirin for 12 or 24 weeks and completed a self-administered behavioural questionnaire at each study visit. The impact of time in treatment and follow-up on longitudinally measured recent (past month) behavioural outcomes was evaluated using generalized estimating equations.Results: Among 93 enrolled participants (83% male, median age 41 years), 55 (59%) had injected in the past month. Any injecting drug use decreased during HCV treatment and follow-up (OR 0.89 per incremental study visit; 95% CI 0.83-0.95). No significant changes were found in ≥daily injecting (OR 0.98; 95% CI 0.89-1.07), use of non-sterile needles (OR 0.94; 95% CI 0.79-1.12), sharing of injecting paraphernalia (OR 0.87; 95% CI 0.70-1.07) or non-injecting drug use (OR 1.01; 95% CI 0.92-1.10). Hazardous alcohol use decreased throughout (OR 0.56; 95% CI 0.40-0.77) and OST increased between enrolment and end of treatment (OR 1.48; 95% CI 1.07-2.04).Conclusions: Recent injecting drug use and hazardous alcohol use decreased, while OST increased during and following HCV treatment among participants with ongoing injecting drug use. These findings support further expansion of HCV care among PWID. [ABSTRACT FROM AUTHOR]

Background Simple, affordable diagnostic tools are essential to facilitate global hepatitis C virus (HCV) elimination efforts. Objectives This study evaluated the clinical performance of core antigen (HCVcAg) assay from plasma samples to monitor HCV treatment efficacy and HCV viral recurrence. Study design Plasma samples from a study of response-guided pegylated-interferon/ribavirin therapy for people who inject drugs with chronic HCV genotype 2/3 infection were assessed for HCV RNA (AmpliPrep/COBAS Taqman assay, Roche) and HCVcAg (ARCHITECT HCV Ag, Abbott Diagnostics) during and after therapy. The sensitivity and specificity of the HCVcAg assay was compared to the HCV RNA assay (gold standard). Results A total of 335 samples from 92 enrolled participants were assessed (mean 4 time-points per participant). At baseline, end of treatment response (ETR) and sustained virological response (SVR) visits, the sensitivity of the HCVcAg assay with quantifiable HCV RNA threshold was 94% (95% CI: 88%, 98%), 56% (21%, 86%) and 100%, respectively. The specificity was between 98 to 100% for all time-points assessed. HCVcAg accurately detected all six participants with viral recurrence, demonstrating 100% sensitivity and specificity. One participant with detectable (non-quantifiable) HCV RNA and non-reactive HCVcAg at SVR12 subsequently cleared HCV RNA at SVR24. Conclusions HCVcAg demonstrated high sensitivity and specificity for detection of pre-treatment and post-treatment viraemia. This study indicates that confirmation of active HCV infection, including recurrent viraemia, by HCVcAg is possible. Reduced on-treatment sensitivity of HCVcAg may be a clinical advantage given the moves toward simplification of monitoring schedules. [ABSTRACT FROM AUTHOR]

Background: Awareness of hepatitis C virus (HCV) infection status among people who inject drugs (PWID) can empower people with diagnosis, enable treatment uptake, and facilitate elimination. We aimed to evaluate awareness of HCV infection status among a large national cohort of PWID in an era of unrestricted HCV treatment.Methods: ETHOS Engage is an observational cohort study of PWID attending drug treatment clinics and needle and syringe programs in Australia. Participants completed a questionnaire containing self-reported HCV data (including infection status: never tested, tested/unknown, no current HCV infection [HCV RNA not detectable], current HCV infection [HCV RNA detectable]) and underwent point-of-care HCV RNA testing (Xpert® HCV Viral Load Fingerstick). Awareness was defined as concordant self-reported HCV status and test result. Awareness was assessed among all participants, those with current HCV infection, and participants who reported a lifetime history of HCV treatment. Logistic regression was used to assess factors associated with awareness in these three populations.Results: Among 2,305 PWID, 65% (n=1,506) were aware of their HCV infection status (self-reported HCV status matched HCV point-of-care result). Awareness of infection status was higher among those who were not currently infected (70%, n=1,281/1,818) compared to those with current HCV infection (46%, n=225/487). After adjusting, those with current HCV infection were less likely to be aware of infection status (aOR: 0.40, 95%CI: 0.30, 0.45). Among those who reported a lifetime history of HCV treatment, 71% (n=592/829) were aware of their HCV infection status.Conclusion: Among a large cohort of PWID in Australia, awareness of HCV infection status is sub-optimal, with particularly concerning levels among those with active infection. Increased and simplified testing, post-test counselling, and post-treatment monitoring is warranted. [ABSTRACT FROM AUTHOR]

Background & Aims We determined the optimal HCV treatment prioritization strategy for interferon-free (IFN-free) HCV direct-acting antivirals (DAAs) by disease stage and risk status incorporating treatment of people who inject drugs (PWID). Methods A dynamic HCV transmission and progression model compared the cost-effectiveness of treating patients early vs. delaying until cirrhosis for patients with mild or moderate fibrosis, where PWID chronic HCV prevalence was 20, 40 or 60%. Treatment duration was 12 weeks at £3300/wk, to achieve a 95% sustained viral response and was varied by genotype/stage in alternative scenarios. We estimated long-term health costs (in £UK = €1.3 = $1.5) and outcomes as quality adjusted life-years (QALYs) gained using a £20,000 willingness to pay per QALY threshold. We ranked strategies with net monetary benefit (NMB); negative NMB implies delay treatment. Results The most cost-effective group to treat were PWID with moderate fibrosis (mean NMB per early treatment £60,640/£23,968 at 20/40% chronic prevalence, respectively), followed by PWID with mild fibrosis (NMB £59,258 and £19,421, respectively) then ex-PWID/non-PWID with moderate fibrosis (NMB £9,404). Treatment of ex-PWID/non-PWID with mild fibrosis could be delayed (NMB -£3,650). In populations with 60% chronic HCV among PWID it was only cost-effective to prioritize DAAs to ex-PWID/non-PWID with moderate fibrosis. For every one PWID in the 20% chronic HCV setting, 2 new HCV infections were averted. One extra HCV-related death was averted per 13 people with moderate disease treated. Rankings were unchanged with reduced drug costs or varied sustained virological response/duration by genotype/fibrosis stage. Conclusions Treating PWID with moderate or mild HCV with IFN-free DAAs is cost-effective compared to delay until cirrhosis, except when chronic HCV prevalence and reinfection risk is very high. [ABSTRACT FROM AUTHOR]

The aim of this study was to identify factors associated with phylogenetic clustering among people with recently acquired hepatitis C virus (HCV) infection. Participants with available sample at time of HCV detection were selected from three studies; the Australian Trial in Acute Hepatitis C, the Hepatitis C Incidence and Transmission Study — Prison and Community. HCV RNA was extracted and Core to E2 region of HCV sequenced. Clusters were identified from maximum likelihood trees with 1000 bootstrap replicates using 90% bootstrap and 5% genetic distance threshold. Among 225 participants with available Core-E2 sequence (ATAHC, n = 113; HITS-p, n = 90; and HITS-c, n = 22), HCV genotype prevalence was: G1a: 38% (n = 86), G1b: 5% (n = 12), G2a: 1% (n = 2), G2b: 5% (n = 11), G3a: 48% (n = 109), G6a: 1% (n = 2) and G6l 1% (n = 3). Of participants included in phylogenetic trees, 22% of participants were in a pair/cluster (G1a-35%, 30/85, mean maximum genetic distance = 0.031; G3a-11%, 12/106, mean maximum genetic distance = 0.021; other genotypes-21%, 6/28, mean maximum genetic distance = 0.023). Among HCV/HIV co-infected participants, 50% (18/36) were in a pair/cluster, compared to 16% (30/183) with HCV mono-infection (P = < 0.001). Factors independently associated with phylogenetic clustering were HIV co-infection [vs. HCV mono-infection; adjusted odds ratio (AOR) 4.24; 95%CI 1.91, 9.39], and HCV G1a infection (vs. other HCV genotypes; AOR 3.33, 95%CI 0.14, 0.61).HCV treatment and prevention strategies, including enhanced antiviral therapy, should be optimised. The impact of targeting of HCV treatment as prevention to populations with higher phylogenetic clustering, such as those with HIV co-infection, could be explored through mathematical modelling. [ABSTRACT FROM AUTHOR]