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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]

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. [ABSTRACT FROM AUTHOR]

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

Background: Bacterial meningitis is a medical emergency and timely management has been shown to improve outcomes. The aim of this study was to compare the early assessment and management of adults with suspected community‐onset meningitis between hospitals and identify opportunities for clinical practice improvement. Methods: This retrospective cohort study was conducted at three principal referral hospitals in Sydney, Australia. Adult patients with suspected meningitis undergoing cerebrospinal fluid sampling between 1 July 2018 and 31 June 2019 were included. Relevant clinical and laboratory data were extracted from the medical record. Differences between sites were analysed and factors associated with time to antimicrobial therapy were assessed by Cox regression. Results: In 260 patients, the median time from triage to antibiotic administration was 332 min with a difference of up to 147 min between hospitals. Median time from triage to lumbar puncture (LP) was 366 min with an inter‐hospital difference of up to 198 min. Seventy per cent of patients had neuroimaging prior to LP, and this group had a significantly longer median time to antibiotic administration (367 vs 231 min; P = 0.001). Guideline concordant antibiotics were administered in 84% of patients, with only 39% of those administered adjunctive corticosteroids. Seven (3%) patients had confirmed bacterial meningitis. Modifiable factors associated with earlier antimicrobial administration included infectious diseases involvement (adjusted hazard ratio [aHR], 1.50 [95% confidence interval (CI), 1.01–2.24]) and computed tomography (CT) scanning (aHR, 0.67 [95% CI, 0.46–0.98]). Conclusion: Opportunities for improvement include reducing the time to LP and antibiotic administration, improving coadministration of corticosteroids and avoiding potentially unnecessary CT scanning. [ABSTRACT FROM AUTHOR]

Introduction: Exploration of sexual and drug use behaviours following treatment for recent hepatitis C virus (HCV) is limited. This analysis modelled behavioural trajectories following treatment for recent HCV and assessed reinfection. Methods: Participants treated for recent HCV in an international trial (enrolled 2017–2019) were followed at 3‐monthly intervals for up to 2 years to assess longitudinal behaviours. Population‐averaged changes were assessed using generalized estimating equations. Distinct behavioural trajectories were identified using group‐based trajectory modelling. HCV reinfection incidence was calculated using person‐years (PY) of observation. Results: During the follow‐up of 212 participants (84% gay and bisexual men [GBM]; 69% HIV; 26% current injecting drug use [IDU]), behavioural trajectories for IDU and stimulant use (past month) did not change. However, population‐averaged decreases in the likelihood of daily IDU (adjusted odds ratio [AOR] 0.83; 95% CI 0.72, 0.95) and opioid use (AOR 0.84; 95% CI 0.75, 0.93) were observed. Among GBM, behavioural trajectories for chemsex did not change. Population‐averaged decreases in condomless anal intercourse with casual male partners (CAI‐CMP) (AOR 0.95; 95% CI 0.90, 0.99) and group‐sex (AOR 0.86; 95% CI 0.80, 0.93) were observed, but masked distinct trajectories. While a proportion had a decreased probability of CAI‐CMP (23%) and group‐sex (59%) post‐treatment, a substantial proportion retained a high probability of these behaviours. High HCV reinfection incidence was observed for the sustained high probability IDU (33.0/100 PY; 95% CI 17.7, 61.3) and chemsex (23.3/100 PY; 95% CI 14.5, 37.5) trajectories. Conclusions: Limited sexual and drug use behavioural change was observed following treatment for recent HCV, supporting access to surveillance and (re)treatment. [ABSTRACT FROM AUTHOR]

Objectives: SARS‐CoV‐2 infection causes a spectrum of clinical disease presentation, ranging from asymptomatic to fatal. While neutralising antibody (NAb) responses correlate with protection against symptomatic and severe infection, the contribution of the T‐cell response to disease resolution or progression is still unclear. As newly emerging variants of concern have the capacity to partially escape NAb responses, defining the contribution of individual T‐cell subsets to disease outcome is imperative to inform the development of next‐generation COVID‐19 vaccines. Methods: Immunophenotyping of T‐cell responses in unvaccinated individuals was performed, representing the full spectrum of COVID‐19 clinical presentation. Computational and manual analyses were used to identify T‐cell populations associated with distinct disease states. Results: Critical SARS‐CoV‐2 infection was characterised by an increase in activated and cytotoxic CD4+ lymphocytes (CTL). These CD4+ CTLs were largely absent in asymptomatic to severe disease states. In contrast, non‐critical COVID‐19 was associated with high frequencies of naïve T cells and lack of activation marker expression. Conclusion: Highly activated and cytotoxic CD4+ T‐cell responses may contribute to cell‐mediated host tissue damage and progression of COVID‐19. Induction of these potentially detrimental T‐cell responses should be considered when developing and implementing effective COVID‐19 control strategies. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

The long‐term health consequences of severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) infection are still being understood. The molecular and phenotypic properties of SARS‐CoV‐2 antigen–specific T cells suggest a dysfunctional profile that persists in convalescence in those who were severely ill. By contrast, the antigen‐specific memory B‐cell (MBC) population has not yet been analyzed to the same degree, but phenotypic analysis suggests differences following recovery from mild or severe coronavirus disease 2019 (COVID‐19). Here, we performed single‐cell molecular analysis of the SARS‐CoV‐2 receptor‐binding domain (RBD)–specific MBC population in three patients after severe COVID‐19 and four patients after mild/moderate COVID‐19. We analyzed the transcriptomic and B‐cell receptor repertoire profiles at ~2 months and ~4 months after symptom onset. Transcriptomic analysis revealed a higher level of tumor necrosis factor‐alpha (TNF‐α) signaling via nuclear factor‐kappa B in the severe group, involving CD80, FOS, CD83 and TNFAIP3 genes that was maintained over time. We demonstrated the presence of two distinct activated MBCs subsets based on expression of CD80hiTNFAIP3hi and CD11chiCD95hi at the transcriptome level. Both groups revealed an increase in somatic hypermutation over time, indicating progressive evolution of humoral memory. This study revealed distinct molecular signatures of long‐term RBD‐specific MBCs in convalescence, indicating that the longevity of these cells may differ depending on acute COVID‐19 severity. [ABSTRACT FROM AUTHOR]

Individuals who spontaneously clear hepatitis C virus (HCV) infection have demonstrated evidence of partial protective immunity, whereas treatment‐induced clearance provides little or no protection against reinfection. We aimed to investigate whether treatment of acute HCV infection with direct‐acting antivirals (DAA) prevents establishment of, or reverses, T‐cell exhaustion, leading to a virus‐specific T‐cell immune profile more similar to that seen in spontaneous clearance. The magnitude and breadth of HCV‐specific T‐cell responses before and after DAA or interferon‐based therapy in acute or chronic HCV were compared to those of participants with spontaneous clearance of infection, using Enzyme‐linked Immunospot (ELISPOT). PBMCs were available for 55 patients comprising 4 groups: spontaneous clearance (n = 17), acute interferon (n = 14), acute DAA (n = 13) and chronic DAA (n = 11). After controlling for sex, the magnitude of post‐treatment HCV‐specific responses after acute DAA treatment was greater than after chronic DAA or acute IFN treatment and similar to those found in spontaneous clearers. However, spontaneous clearers responded to more HCV peptide pools indicating greater breadth of response. In conclusion, early treatment with DAAs may prevent or reverse some degree of immune exhaustion and result in stronger HCV‐specific responses post‐treatment. However, individuals with spontaneous clearance had broader HCV‐specific responses. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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 = 10,843) 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 decentralized models may increase retreatment uptake and reduce HCV‐related mortality. [ABSTRACT FROM AUTHOR]

People living with HIV (PLHIV) are a priority population to receive hepatitis C virus (HCV) screening and treatment. We aimed to characterize the HCV care cascade among PLHIV between 2010 and 2018 and to compare HCV testing and treatment uptake pre‐ and post‐availability of direct‐acting antivirals (DAAs) in New South Wales (NSW), Australia. Records of all HCV notifications (1993–2017) were linked to HIV notifications, deaths, hospitalizations, incarcerations, opioid agonist therapy, HCV RNA testing and treatment databases. Numbers and proportions were calculated for all stages of the care cascade and factors associated with HCV testing, and DAA treatment uptake were evaluated using logistic regression. From 383 individuals with HCV notification (2009–2017), 349 (91%) were ever HCV RNA tested, 285 (74%) had an indicator of chronic HCV infection, and from those eligible for treatment, 210 (74%) received HCV treatment. HCV testing was recorded for 85% pre‐DAA era and reached a cumulative proportion of 90% post‐DAA while treatment uptake had a 10‐fold increase from 7% pre‐ to 73% post‐DAA era. Younger age (adjusted odds ratio [aOR] 0.98; 95% CI 0.96–0.99), female gender (aOR 1.87; 95% CI 1.10–3.19), and rural region residence at notification (aOR 1.56; 95% CI 1.03–2.36) were associated with not receiving HCV testing. No identified factor was associated with not receiving treatment post‐DAA era. Removing barriers to HCV testing, expanding treatment to a variety of settings and continuous education and harm reduction are essential to achieve HCV elimination among PLHIV in Australia. [ABSTRACT FROM AUTHOR]

We sought to characterize risk factors and patterns of HCV transmission amongst men who have sex with men (MSM). MSM with recently acquired HCV (AHCV) were prospectively recruited ('clinic cohort') between January and September 2017. Clinical data and risk behaviours were identified and blood obtained for HCV whole genome sequencing. Phylogenetic analyses were performed, using sequences from this cohort and two other AHCV cohorts, to identify transmission clusters. Sixteen (40.0%) men in the clinic cohort were HIV‐negative MSM. HIV‐negative MSM were younger than HIV‐positive MSM; most (81.3%) had taken HIV PrEP in the preceding year. Eighteen men (45.0%) reported injection drug use; most (34, 85.0%) reported noninjection drug use in the last year. Most in both groups reported condomless anal sex, fisting and sex in a group environment. Few (7, 17.5%) men thought partners may have had HCV. There were 52 sequences in the HCV genotype 1a phylogeny, 18 from the clinic cohort and 34 from other AHCV cohorts; 47 (90.4%) clustered with ≥1 other sequence. There were 7 clusters of 2‐27 sequences; 6 clusters contained HIV‐negative and HIV‐positive MSM and 1 cluster only HIV‐positive MSM. Four of these clusters were part of larger clusters first described in 2007. PrEP‐using MSM are at risk of HCV, sharing similar risk factors to HIV‐positive MSM. Phylogenetics highlights that PrEP‐using and HIV‐positive MSM are involved in the same HCV transmission networks. Few men demonstrated HCV awareness and risk reduction strategies should be expanded. [ABSTRACT FROM AUTHOR]

People who are homeless have increased hepatitis C virus (HCV) infection risk, and are less likely to access primary healthcare. We aimed to evaluate HCV RNA prevalence, liver disease burden, linkage to care and treatment uptake and outcomes among people attending a homelessness service in Sydney. Participants were enrolled in an observational cohort study with recruitment at a homelessness service over eight liver health campaign days. Finger‐stick whole‐blood samples for Xpert® HCV Viral Load and venepuncture blood samples were collected. Participants completed a self‐administered survey and received transient elastography and clinical assessment by a general practitioner or nurse. Clinical follow‐up was recommended 2‐12 weeks after enrolment. For participants initiating direct‐acting antiviral (DAA) therapy, medical records were audited retrospectively and treatment outcome data were collected. Among 202 participants (mean age, 48 years), 82% were male (n = 165), 39% (n = 78) reported ever injecting drugs, of whom 63% (n = 49) injected in the previous month. Overall, 23% (n = 47) had detectable HCV RNA and 6% (n=12) had cirrhosis. HCV RNA prevalence among participants with either injecting or incarceration history was 35% (37/105), compared to 4% (3/73) among participants without these risk factors. Among those with detectable HCV RNA, 23 (49%) commenced therapy, of whom 65% (n = 15) achieved sustained virological response, while the remainder had no available treatment outcome. No participant had documented virological failure. HCV DAA treatment uptake among people attending a homelessness service was encouraging, but innovative models of HCV care are required to improve linkage to care and treatment uptake among this highly marginalized population. [ABSTRACT FROM AUTHOR]

Keywords: Hepatitis; viral; Treatment outcome; General practice; Hepatitis C EN Hepatitis viral Treatment outcome General practice Hepatitis C 332 333 2 10/05/21 20211001 NES 211001 In Australia, highly effective direct-acting antiviral (DAA) therapy has been available for people with chronic hepatitis C through the Pharmaceutical Benefits Scheme (PBS) since March 2016. Prescribing of direct-acting antiviral therapy by general practitioners for people with hepatitis C in an unrestricted treatment program Almost half the prescribing GPs (48%, 2986 of 6187) and 14% of prescribing specialists (112 of 811) had prescribed DAA therapy for one patient only; 10% of GP prescribers (630 of 6187) and 58% of specialist prescribers (469 of 811) had treated ten or more patients (Box 2, C). [Extracted from the article]

Keywords: Hepatitis C EN Hepatitis C 362 363 2 05/05/20 20200515 NES 200515 Early empirical evidence provides grounds for optimism about eliminating HCV by 2030 Curative direct-acting antiviral (DAA) therapy for people with chronic hepatitis C virus (HCV) infections[1] has transformed clinical management and spurred ambitious World Health Organization elimination targets for 2030.[2] WHO service targets encompass marked improvements in prevention, diagnosis, and treatment; impact targets include a 65% reduction in HCV-related deaths and an 80% reduction in new HCV infections compared with 2015.[2] In 2015, an estimated 71 million people were living with chronic HCV infection. First, our recent downward revision of the estimated number of people with chronic HCV infection in 2015, from 227 000 to 188 000 (largely because of duplicate HCV notifications), means that the starting point for HCV elimination is 17% lower. Declining hepatitis C virus-related liver disease burden in the direct-acting antiviral therapy era in New South Wales, Australia. [Extracted from the article]

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]

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]