Sex and gender differences in hepatitis C virus risk, prevention, and cascade of care in people who inject drugs: systematic review and meta-analysis.

Background: People who inject drugs (PWID) are a priority population in HCV elimination programming. Overcoming sex and gender disparities in HCV risk, prevention, and the cascade of care is likely to be important to achieving this goal, but these have not yet been comprehensively reviewed. Methods: Systematic review and meta-analysis. We searched Pubmed, EMBASE and the Cochrane Database of Systematic Reviews 1 January 2012-22 January 2024 for studies of any design reporting sex or gender differences among PWID in at least one of: sharing of needles and/or syringes, incarceration history, injection while incarcerated, participation in opioid agonist treatment or needle and syringe programs, HCV testing, spontaneous HCV clearance, direct-acting antiviral (DAA) treatment initiation or completion, and sustained virological response (SVR). Assessment of study quality was based on selected aspects of study design. Additional data were requested from study authors. Data were extracted in duplicate and meta-analysed using random effects models. PROSPERO registration CRD42022342806. Findings: 9533 studies were identified and 92 studies were included. Compared to men, women were at greater risk for receptive needle and syringe sharing (past 6-12 months: risk ratio (RR) 1.12; 95% confidence interval (CI) 1.01-1.23; <6 months: RR 1.38; 95% CI 1.09-1.76), less likely to be incarcerated (lifetime RR 0.64; 95% CI 0.57-0.73) more likely to be tested for HCV infection (lifetime RR 1.07; 95% CI 1.01, 1.14), more likely to spontaneously clear infection (RR1.58; 95% CI 1.40-1.79), less likely to initiate DAA treatment (0.84; 95% CI 0.78-0.90), and more likely to attain SVR after completing DAA treatment (RR 1.02; 95% CI 1.01-1.04). Interpretation: There are important differences in HCV risk and cascade of care indicators among people who inject drugs that may impact the effectiveness of prevention and treatment programming. Developing and assessing the effectiveness of gender-specific and gender-responsive HCV interventions should be a priority in elimination programming. Funding: Réseau SIDA-MI du Québec.

Factors associated with hepatitis C testing, treatment, and current hepatitis C infection among men and women who inject drugs: The ETHOS engage study.

BACKGROUND: 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. METHOD: 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. RESULTS: 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) CONCLUSION: 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.

Needle and syringe sharing among people who have recently injected drugs in Australia: The ETHOS Engage Study.

INTRODUCTION: Understanding needle/syringe sharing is crucial for reducing hepatitis C virus (HCV) infection and reinfection. This study aimed to assess the prevalence and factors associated with needle/syringe sharing among people who inject drugs in Australia, including those previously receiving HCV treatment. METHODS: The ETHOS Engage study was an observational cohort study which collected self-reported survey data on demographic and drug use information from people who inject drugs attending drug treatment clinics and needle and syringe programs over two waves between May 2018 and June 2021. Logistic regression was used to identify factors associated with needle/syringe sharing. RESULTS: Overall, 1555/2395 people enrolled in ETHOS Engage (65%) injected drugs in the past month. Among these, 432 (28%) reported needle/syringe sharing in the past month and 276 (18%) reported receptive sharing. Factors associated with receptive sharing included younger age (adjusted odds ratio [aOR] 1.72; 95% confidence interval [CI] 1.28-2.30), recent incarceration (aOR 2.04; 95% CI 1.40-2.94), more frequent injecting (≥daily vs. less than weekly; aOR 2.59; 95% CI 1.75-3.84) and unstable housing (aOR 1.78; 95% CI 1.26-2.52). Among 560 participants with prior HCV treatment, 87 (16%) reported receptive sharing with younger age (aOR 2.42; 95% CI 1.45-4.05) and daily or greater injection frequency (aOR 2.51; 95% CI 1.31-4.83) associated with receptive sharing. DISCUSSION AND CONCLUSIONS: Needle/syringe sharing was common among this population accessing harm reduction services. This study identifies high-risk populations with needle/syringe sharing. Research is needed to optimise HCV treatment to ensure people with ongoing risk behaviours receive adequate harm reduction following treatment to prevent reinfection.

Chlamydia retesting remains low among young women in Australia: an observational study using sentinel surveillance data, 2018-2022.

BACKGROUND: Chlamydia remains the most notified bacterial sexually transmissible infection in Australia with guidelines recommending testing for re-infection at 3months post treatment. This paper aimed to determine chlamydia retesting and repeat positivity rates within 2-4months among young women in Australia, and to evaluate what factors increase or decrease the likelihood of retesting. METHODS: Chlamydia retesting rates among 16-29-year-old women were analysed from Australian Collaboration for Coordinated Enhanced Sentinel Surveillance of sexually transmissible infection and bloodborne virus (ACCESS) sentinel surveillance data (n =62 sites). Among women with at least one positive test between 1 January 2018 and 31 August 2022, retesting counts and proportions within 2-4months were calculated. Logistic regression was performed to assess factors associated with retesting within 2-4months. RESULTS: Among 8758 women who were positive before 31 August 2022 to allow time for follow up, 1423 (16.2%) were retested within 2-4months, of whom 179 (12.6%) tested positive. The odds of retesting within 2-4months were 25% lower if tested in a coronavirus disease 2019 (COVID-9) pandemic year (2020-2022) (aOR=0.75; 95% CI 0.59-0.95). Among 9140 women with a positive test before 30 November 2022, 397 (4.3%) were retested too early (within 7days to 1month) and 81 (20.4%) of those were positive. CONCLUSIONS: Chlamydia retesting rates remain low with around a sixth of women retested within 2-4months in line with guidelines. Re-infection is common with around one in eight retesting positive. An increase in retesting is required to reduce the risk of reproductive complications and onward transmission.

Testing, diagnosis, and treatment following the implementation of a program to provide dried blood spot testing for HIV and hepatitis C infections: the NSW DBS Pilot.

BACKGROUND: Dried blood spot (DBS) testing provides an alternative to phlebotomy and addresses barriers to accessing healthcare experienced by some key populations. Large-scale evaluations of DBS testing programs are needed to understand their feasibility. This study evaluated the implementation of a state-wide DBS HIV and hepatitis C virus (HCV) testing pilot. METHODS: The New South Wales (NSW) DBS Pilot is an interventional cohort study of people testing for HIV antibody and/or HCV RNA from DBS samples in NSW, Australia. Participants at risk of HIV/HCV participated in testing via: 1) self-registration online with a DBS collection kit delivered and returned by conventional postal service; or 2) assisted DBS sample collection at 36 community health sites (including drug treatment and harm-minimisation services) and prisons. Participants received results by text (HIV antibody/ HCV RNA not detected) or a healthcare provider (HIV antibody/ HCV RNA detected). The RE-AIM framework was used to evaluate reach, effectiveness, adoption, and implementation. RESULTS: Reach: Between November 2016 and December 2020, 7,392 individuals were tested for HIV and/or HCV (21% self-registration, 34% assisted in community, and 45% assisted in prison). EFFECTIVENESS: Of 6,922 people tested for HIV (19% men who have sex with men, 13% living outside major cities, 21% born outside Australia), 51% (3,521/6,922) had no HIV test in the past two years, 0.1% (10/6,922) were newly diagnosed with HIV, and 80% (8/10) initiated HIV treatment within six months. Of 5,960 people tested for HCV (24% women, 35% Aboriginal and/or Torres Strait Islander, 55% recently injected drugs), 15% had detectable HCV RNA (878/5,960), and 45% (393/878) initiated treatment within six months. Adoption: By the end of 2020, DBS via assisted registration was available at 36 community sites and 21 prisons. IMPLEMENTATION: 90% of DBS cards arriving at the laboratory had the three full spots required for testing; the proportion was higher in assisted (94%) compared to online (76%) registration. CONCLUSIONS: This study demonstrated the feasibility of DBS testing for HIV and HCV in key populations including Aboriginal and Torres Strait Islander peoples, men who have sex with men, people who inject drugs, and demonstrated the utility of DBS in the prison setting.

Health-Related Quality of Life of People Who Inject Drugs: The Enhancing Treatment of Hepatitis C in Opioid Substitution Settings Engage Study.

OBJECTIVES: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Hepatitis C Treatment Uptake Following Dried Blood Spot Testing for Hepatitis C RNA in New South Wales, Australia: The NSW DBS Pilot Study.

Background: Dried blood spot (DBS) testing for hepatitis C virus (HCV) RNA provides a sampling option that avoids venepuncture and can be carried out in a nonclinical setting. Large-scale evaluations are needed to understand how DBS testing can reduce HCV burden. This study estimated prevalence of, and factors associated with, HCV RNA and treatment initiation among people enrolled in a state-wide pilot of people testing in the NSW DBS Pilot in New South Wales, Australia. Methods: People at risk of HIV/HCV could participate via (1) self-registration online with a DBS collection kit delivered and returned by conventional postal service; or (2) assisted DBS sample collection at a community site or prison. Logistic regression was used to identify factors associated with detectable HCV RNA and treatment initiation within 6 months of testing. Results: Between September 2017 and December 2020, 5960 people were tested for HCV (76% men, 35% Aboriginal and/or Torres Strait Islander, 55% recently injected drugs): 21% online self-registration, 34% assisted registration in the community, 45% assisted registration in prison. Fifteen percent had detectable HCV RNA (878/5960). Overall, 44% (n = 386/878) of people with current HCV initiated treatment within 6 months (13% online self-registration, 27% assisted registration in the community, 61% assisted registration in prison). Testing in prison compared with the community (adjusted odds ratio [aOR], 4.28; 95% CI, 3.04-6.03) was associated with increased odds of treatment initiation. Being a woman compared with a man (aOR, 0.68; 95% CI, 0.47-0.97) was associated with reduced treatment initiation. Conclusions: The NSW DBS Pilot demonstrates the feasibility of using DBS to promote HCV testing and treatment in community and prison settings.

Evaluating the prevalence of current hepatitis C infection and treatment among Aboriginal and Torres Strait Islander peoples who inject drugs in Australia: The ETHOS engage study.

INTRODUCTION: 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. METHODS: 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. RESULTS: 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. DISCUSSION AND CONCLUSIONS: Equitable access to HCV care and prevention is needed to ensure Australia meets its elimination targets among Aboriginal PWID.

Single-visit hepatitis C point-of-care testing, linkage to nursing care, and peer-supported treatment among people with recent injecting drug use at a peer-led needle and syringe program: The TEMPO Pilot Study.

BACKGROUND: Point-of-care hepatitis C virus (HCV) RNA testing can facilitate single-visit diagnosis and treatment. This study evaluated a single-visit test and treat intervention integrating point-of-care HCV RNA testing, linkage to nursing care, and peer-supported engagement/delivery of treatment among people with recent injecting drug use at a peer-led needle and syringe program (NSP). METHODS: TEMPO Pilot is an interventional cohort study of people with recent injecting drug use (previous month) recruited between September 2019-February 2021 from one peer-led NSP in Sydney, Australia. Participants received point-of-care HCV RNA testing (Xpert HCV Viral Load Fingerstick), linkage to nursing care, and peer-supported engagement/delivery of treatment. The primary endpoint was the proportion initiating HCV therapy. RESULTS: Among 101 people with recent injecting drug use (median age 43; 31% female), 27% (n = 27) were HCV RNA detectable. Treatment uptake was 74% (20 of 27; sofosbuvir/velpatasvir, n = 8; glecaprevir/pibrentasvir, n = 12). Among people initiating treatment (n = 20), 45% (n = 9) initiated treatment at the same visit, 50% (n = 10) in the next 1-2 days, and 5% on day 7 (n = 1). Two participants initiated treatment outside the study (overall treatment uptake 81%). Reasons for not initiating treatment included loss to follow-up (n = 2), no reimbursement (n = 1), not suitable for treatment (mental health) (n = 1), and inability to perform liver disease assessment (n = 1). In the full analysis set, 60% (12 of 20) completed treatment and 40% (8 of 20) had a sustained virological response (SVR). In the evaluable population (excluding people without an SVR test), SVR was 89% (8 of 9). CONCLUSION: Point-of-care HCV RNA testing, linkage to nursing, and peer-supported engagement/delivery led to high HCV treatment uptake (majority single-visit) among people with recent injecting drug use attending a peer-led NSP. The lower proportion of people with SVR highlights the need for further interventions to support treatment completion.

Infectious syphilis in women and heterosexual men in major Australian cities: sentinel surveillance data, 2011-2019.

OBJECTIVES: To examine changes in the positive infectious syphilis test rate among women and heterosexual men in major Australian cities, and rate differences by social, biomedical, and behavioural determinants of health. DESIGN, SETTING: Analysis of data extracted from de-identified patient records from 34 sexual health clinics participating in the Australian Collaboration for Coordinated Enhanced Sentinel Surveillance of Sexually Transmissible Infections and Blood Borne Viruses (ACCESS). PARTICIPANTS: First tests during calendar year for women and heterosexual men aged 15 years or more in major cities who attended ACCESS sexual health clinics during 2011-2019. MAIN OUTCOME MEASURES: Positive infectious syphilis test rate; change in annual positive test rate. RESULTS: 180 of 52 221 tested women (0.34%) and 239 of 36 341 heterosexual men (0.66%) were diagnosed with infectious syphilis. The positive test rate for women was 1.8 (95% confidence interval [CI], 0.9-3.2) per 1000 tests in 2011, 3.0 (95% CI, 2.0-4.2) per 1000 tests in 2019 (change per year: rate ratio [RR], 1.12; 95% CI, 1.01-1.25); for heterosexual men it was 6.1 (95% CI, 3.8-9.2) per 1000 tests in 2011 and 7.6 (95% CI, 5.6-10) per 1000 tests in 2019 (RR, 1.10; 95% CI, 1.03-1.17). In multivariable analyses, the positive test rate was higher for women (adjusted RR [aRR], 1.85; 95% CI, 1.34-2.55) and heterosexual men (aRR, 2.39; 95% CI, 1.53-3.74) in areas of greatest socio-economic disadvantage than for those in areas of least socio-economic disadvantage. It was also higher for Indigenous women (aRR, 2.39; 95% CI, 1.22-4.70) and for women who reported recent injection drug use (aRR, 4.87; 95% CI, 2.18-10.9) than for other women; it was lower for bisexual than heterosexual women (aRR, 0.48; 95% CI, 0.29-0.81) and for women who reported recent sex work (aRR, 0.35; 95% CI, 0.29-0.44). The positive test rate was higher for heterosexual men aged 40-49 years (aRR, 2.11; 95% CI, 1.42-3.12) or more than 50 years (aRR, 2.36; 95% CI, 1.53-3.65) than for those aged 15-29 years. CONCLUSION: The positive test rate among both urban women and heterosexual men tested was higher in 2019 than in 2011. People who attend reproductive health or alcohol and drug services should be routinely screened for syphilis.

Effectiveness of direct-acting antiviral therapy among Aboriginal and Torres Strait Islander peoples with HCV infection in Australia: A national real-world cohort (REACH-C).

Aboriginal and Torres Strait Islander peoples experience a disproportionate burden of hepatitis C virus (HCV) infection. This study assessed the effectiveness of direct-acting antiviral (DAA) therapy among Aboriginal peoples in the three years following universal access in Australia. REACH-C, a national multicentre prospective cohort study, evaluated HCV treatment outcomes from sequential DAA initiations across 33 health services between March 2016 and June 2019. DAA effectiveness was assessed by sustained virological response (SVR) in the total (full analysis set) and effectiveness (modified analysis set excluding those lost to follow-up) populations. Overall, 915 (10%) Aboriginal and 8095 (90%) non-Indigenous people commenced DAA therapy, of whom 30% and 16% reported current injecting drug use and 73% and 42% were treated in primary care, respectively. SVR in the total and effectiveness populations was 74% and 94% among Aboriginal people and 82% and 94% among non-Indigenous people, with loss to follow-up contributing to lower SVR in the total population analysis (22% Aboriginal, 13% non-Indigenous). Among Aboriginal people, returning for follow-up was positively associated with older age (aOR 1.20; 95% CI 1.04, 1.39) and SVR was negatively associated with cirrhosis (aOR 0.39; 95% CI 0.19, 0.80) and prior DAA treatment (aOR 0.14; 95% CI 0.04, 0.49). Factors reflecting higher vulnerability or inequity were not associated with returning for testing or SVR. DAA therapy was highly effective among Aboriginal peoples with HCV treated through primary and tertiary services. Tailored community-led interventions are necessary to optimize follow-up and engagement. Sustained DAA uptake and equitable access to care, treatment and prevention are required for HCV elimination.

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.

Awareness of HCV Status and Preferences for Testing and Treatment among People with Recent Injecting Drug Use at a Peer-Led Needle and Syringe Program: The TEMPO Pilot Study.

BACKGROUND: New technologies and therapies allow the possibility of a single-visit test and treat model for hepatitis C virus (HCV), addressing some of the barriers to care faced by people who inject drugs. METHODS: The TEMPO Pilot Study was an interventional cohort study evaluating a single-visit test and treat intervention among people with recent injecting drug use at a one peer-led needle and syringe program (NSP) in Sydney, Australia between September 2019 and February 2021. This analysis evaluated awareness of HCV status and agreement of self-report with HCV RNA test results. The analysis also assessed acceptability of: modality of result delivery, modality of blood sampling, site of treatment, and duration of treatment. RESULTS: Among 101 participants (median age 43; 31% female), 100 had a valid HCV RNA test result and 27% (27/100) were HCV RNA detectable. Overall, 65% (65/100) were aware of their status. Among people with a positive HCV RNA result, 48% (13/27) were aware of their status. People preferred same-day HCV test results (95%, 96/101), and preferred to receive results in person (69%, 70/101). Receiving treatment at an NSP was acceptable (100%, 101/101) and 78% (79/101) were willing to discuss their health with a peer NSP worker. CONCLUSION: Half of people with current HCV infection were aware of their status. The high acceptability of simplified testing and treatment pathways delivered at NSPs indicates that this is an appropriate strategy to improve HCV awareness and treatment uptake in this population.

Awareness of hepatitis C virus infection status among people who inject drugs in a setting of universal direct-acting antiviral therapy: The ETHOS Engage study.

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.

Patterns and correlates of hepatitis C virus phylogenetic clustering among people living with HIV in Australia in the direct-acting antiviral era: A molecular epidemiology study among participants in the CEASE cohort.

Background and Aims: In moving towards the elimination of hepatitis C virus (HCV) infection among people living with HIV, understanding HCV transmission patterns may provide insights to guide and evaluate interventions. In this study, we evaluated patterns of, and factors associated with HCV phylogenetic clustering among people living with HIV/HCV co-infection in Australia in the direct-acting antiviral era. Methods: HCV RNA was extracted from dried blood spot (DBS) samples collected between 2014 and 2018 in the CEASE cohort study. The HCV Core-E2 region was amplified by a polymerase chain reaction and Sanger sequenced. Maximum likelihood phylogenetic trees (1000 bootstrap replicates) were used to identify patterns of clustering (3% genetic distance threshold). Mixed-effects logistic regression was used to determine correlates of phylogenetic clustering. Factors assessed were sexual risk behavior, education, injecting drug use, housing, employment, HIV viral load, age, sex, and sexuality. Results: Phylogenetic trees were reconstructed for HCV subtype 1a (n = 139) and 3a (n = 63) sequences, with 29% (58/202) in a pair or cluster. Overall (n = 202), phylogenetic clustering was positively associated with younger age (under 40; adjusted odds ratio [aOR] 2.52, 95% confidence interval [CI] 1.20-5.29), and among gay and bisexual men (n = 168), was positively associated with younger age (aOR 2.61, 95% CI 1.10-6.19), higher education (aOR 2.58, 95% CI 1.09-6.13), and reporting high-risk sexual behavior (aOR 3.94, 95% CI 1.31-11.84). During follow-up, five reinfections were observed, but none were in phylogenetic clusters. Conclusion: This study found a high proportion of phylogenetic relatedness, predominantly among younger people and gay and bisexual men reporting high-risk sexual behavior. Despite this, few reinfections were observed, and reinfections demonstrated little relationship with known clusters. These findings highlight the importance of rapid HCV treatment initiation, together with monitoring of the phylogeny.

A Testing Campaign Intervention Consisting of Peer-Facilitated Engagement, Point-of-Care HCV RNA Testing, and Linkage to Nursing Support to Enhance Hepatitis C Treatment Uptake among People Who Inject Drugs: The ETHOS Engage Study.

This study evaluated HCV treatment initiation among people who inject drugs (PWID) following an intervention of campaign days involving peer connection, point-of-care HCV RNA testing, and linkage to nursing support. ETHOS Engage is an observational cohort study of PWID attending 25 drug treatment clinics and needle and syringe programs in Australia (May 2018-September 2019). Point-of-care results were provided to the nurse, facilitating confirmatory testing and treatment. The study aimed to evaluate treatment uptake and factors associated with treatment at 24 months post-enrolment. There were 317 people with current HCV infection and eligible for treatment (median age 43, 65% male, 15% homeless, 69% receiving opioid agonist treatment, 70% injected in last month). Overall, 15% (47/317), 27% (85/317), 38% (120/317), and 49% (155/317) of people with current HCV infection had initiated treatment at 3-, 6-, 12-, and 24-months following testing, respectively. Homelessness (adjusted hazard ratio (aHR): 0.40; 95% confidence interval: 0.23, 0.71) and incarceration in the past 12 months (vs. never, aHR:0.46; 0.28, 0.76) were associated with decreased treatment initiation in the 24 months post-enrolment. This testing campaign intervention facilitated HCV treatment uptake among PWID. Further interventions are needed to achieve HCV elimination among people experiencing homelessness or incarceration.

Prevalence and factors associated with hospitalisation for bacterial skin infections among people who inject drugs: The ETHOS Engage Study.

BACKGROUND: Injecting-related skin and soft tissue infections (SSTIs) are a preventable cause of inpatient hospitalisation among people who inject drugs (PWID). This study aimed to determine the prevalence of hospitalisation for SSTIs among PWID, and identify similarities and differences in factors associated with hospitalisation for SSTIs versus non-bacterial harms related to injecting drug use. METHODS: We performed cross-sectional analyses of baseline data from an observational cohort study of PWID attending drug treatment clinics and needle and syringe programs in Australia. Logistic regression models were used to identify factors associated with self-reported hospitalisation for (1) SSTIs (abscess and/or cellulitis), and (2) non-bacterial harms related to injecting drug use (e.g., non-fatal overdose; hereafter referred to as non-bacterial harms), both together and separately. RESULTS: 1851 participants who injected drugs in the previous six months were enrolled (67% male; 85% injected in the past month; 42% receiving opioid agonist treatment [OAT]). In the previous year, 40% (n = 737) had been hospitalised for drug-related causes: 20% (n = 377) and 29% (n = 528) of participants were admitted to hospital for an SSTI and non-bacterial harm, respectively. Participants who were female (adjusted odds ratio [aOR]: 1.53, 95% CI: 1.19-1.97) or homeless (aOR: 1.59, 95% CI: 1.16-2.19) were more likely to be hospitalised for an SSTI, but not a non-bacterial harm. Both types of hospitalisation were more likely among people recently released from prison. CONCLUSIONS: Hospitalisation for SSTIs is common among PWID. Community-based interventions to prevent SSTIs and subsequent hospitalisation among PWID will require targeting of at-risk groups, including women, people experiencing homelessness, and incarcerated people upon prison release.

Declining prevalence of current HCV infection and increased treatment uptake among people who inject drugs: The ETHOS Engage study.

BACKGROUND: Evaluating trends in HCV treatment and prevalence is crucial for monitoring elimination. We evaluated the change in current infection and treatment among people who inject drugs (PWID) between 2018-2019 and 2019-2021. METHODS: ETHOS Engage is an observational cohort study of PWID attending drug treatment clinics and needle and syringe programs in Australia. Participant enrolment occurred over two periods, Wave 1 (May 2018-September 2019, 25 sites) and Wave 2 (November 2019-June 2021, 21 sites), with baseline questionnaire completion and point-of-care HCV RNA testing (Xpert® HCV Viral Load Fingerstick). Logistic regression was used to identify factors associated with current HCV infection and historic HCV treatment. RESULTS: 2,395 individuals were enrolled across the two recruitment waves (66% male, median age 43, 72% current opioid agonist therapy, and 65% injecting in the previous month). HCV prevalence decreased from 24% to 17% between 2018-2019 and 2019-2021, respectively (p=0.003). HCV treatment increased from 66% to 74% between 2018-2019 and 2019-2021, respectively (p<0.001). After adjusting, there was a reduction in current HCV infection in 2019-2021 (adjusted odds ratio [aOR] 0.62; 95% CI, 0.50, 0.77) compared to 2018-2019. Other factors associated with current infection included homelessness (aOR, 1.70; 1.26, 2.30), incarceration (vs. never; historic: aOR 1.69; 95%CI 1.31, 2.19; recent: aOR 1.85; 95%CI, 1.35, 2.54), and recently injecting drugs (vs. >12 months ago; previous month

Retreatment for hepatitis C virus direct acting antiviral therapy virological failure in primary and tertiary settings: the REACH-C cohort.

Virological failure occurs in a small proportion of people treated for hepatitis C virus (HCV) with direct-acting antiviral (DAA) therapies. This study assessed retreatment for virological failure in a large real-world cohort. REACH-C is an Australian observational study (n=10843) evaluating treatment outcomes of sequential DAA initiations across 33 health services between March 2016 to June 2019. Virological failure retreatment data were collected until October 2020. Of 408 people with virological failure (81% male; median age 53; 38% cirrhosis; 56% genotype 3), 213 (54%) were retreated once; 15 were retreated twice. A range of genotype specific and pangenotypic DAAs were used to retreat virological failure in primary (n=56) and tertiary (n=157) settings. Following sofosbuvir/velpatasvir/voxilaprevir availability in 2019, the proportion retreated in primary care increased from 21% to 40% and median time to retreatment initiation declined from 294 to 152 days. Per-protocol (PP) sustained virological response (SVR12) was similar for people retreated in primary and tertiary settings (80% vs 81%; p=1.000). In regression analysis, sofosbuvir/velpatasvir/voxilaprevir (vs. other regimens) significantly decreased likelihood of second virological failure (PP SVR12 88% vs. 77%; adjusted odds ratio [AOR] 0.29; 95%CI 0.11-0.81); cirrhosis increased likelihood (PP SVR12 69% vs. 91%; AOR 4.26; 95%CI 1.64-11.09). Indigenous Australians had lower likelihood of retreatment initiation (AOR 0.36; 95%CI 0.15-0.81). Treatment setting and prescriber type were not associated with retreatment initiation or outcome. Virological failure can be effectively retreated in primary care. Expanded access to simplified retreatment regimens through decentralised models may increase retreatment uptake and reduce HCV-related mortality.