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Background: There is some concern that hepatitis C virus (HCV) reinfection might impact HCV micro-elimination efforts among gay and bisexual men (GBM) with HIV. However, there is a limited understanding of reinfection incidence in the context of unrestricted government-funded HCV treatment. We aimed to estimate HCV reinfection incidence among GBM with HIV in Australia from 2016 to 2020., Methods: Data were from 39 clinics participating in ACCESS, a sentinel surveillance network for blood borne viruses and sexually transmissible infections across Australia. GBM with HIV who had evidence of treatment or spontaneous clearance with at least one positive HCV RNA test, a subsequent negative HCV RNA test, and at least one additional HCV RNA test between 1st January 2016 and 31st December 2020 were eligible for inclusion. A new HCV RNA positive test and/or detectable viral load was defined as a reinfection. Generalised linear modelling was used to examine trends in reinfection., Results: Among 12 213 GBM with HIV who had at least one HCV test, 540 were included in the reinfection incidence analysis, of whom 38 (7%) had evidence of reinfection during the observation period. Over 1124 person-years of follow-up, the overall rate of reinfection was 3.4/100PY (95% CI 2.5-4.6). HCV reinfection incidence declined on average 30% per calendar year (Incidence Rate Ratio 0.70, 95% CI 0.54-0.91)., Conclusion: HCV reinfection incidence has declined among GBM with HIV in Australia since government-funded unrestricted DAAs were made available. Ongoing HCV RNA testing following cure and prompt treatment for anyone newly diagnosed is warranted to sustain this., (© 2024 The Authors. Liver International published by John Wiley & Sons Ltd.)

Background: Reinfection after successful treatment with direct-acting antivirals is hypothesised to undermine efforts to eliminate hepatitis C virus (HCV) infection among people with HIV. We aimed to assess changes in incidence of HCV reinfection among people with HIV following the introduction of direct-acting antivirals, and the proportion of all incident cases attributable to reinfection., Methods: We pooled individual-level data on HCV reinfection in people with HIV after spontaneous or treatment-induced clearance of HCV from six cohorts contributing data to the International Collaboration on Hepatitis C Elimination in HIV Cohorts (InCHEHC) in Australia, Canada, France, the Netherlands, Spain, and Switzerland between Jan 1, 2010, and Dec 31, 2019. Participants were eligible if they had evidence of an HCV infection (HCV antibody or RNA positive test) followed by spontaneous clearance or treatment-induced clearance, with at least one HCV RNA test after clearance enabling measurement of reinfection. We assessed differences in first reinfection incidence between direct-acting antiviral access periods (pre-direct-acting antiviral, limited access [access restricted to people with moderate or severe liver disease and other priority groups], and broad access [access for all patients with chronic HCV]) using Poisson regression. We estimated changes in combined HCV incidence (primary and reinfection) and the relative contribution of infection type by calendar year., Findings: Overall, 6144 people with HIV who were at risk of HCV reinfection (median age 49 years [IQR 42-54]; 4989 [81%] male; 2836 [46%] men who have sex with men; 2360 [38%] people who inject drugs) were followed up for 17 303 person-years and were included in this analysis. The incidence of first HCV reinfection was stable during the period before the introduction of direct-acting antivirals (pre-introduction period; 4·1 cases per 100 person-years, 95% CI 2·8-6·0). Compared with the pre-introduction period, the average incidence of reinfection was 4% lower during the period of limited access (incidence rate ratio [IRR] 0·96, 95% CI 0·78-1·19), and 28% lower during the period of broad access (0·72, 0·60-0·86). Between 2015 and 2019, the proportion of incident HCV infections due to reinfection increased, but combined incidence declined by 34%, from 1·02 cases per 100 person-years (95% CI 0·96-1·07) in 2015 to 0·67 cases per 100 person-years (95% CI 0·59-0·75) in 2019., Interpretation: HCV reinfection incidence and combined incidence declined in people with HIV following direct-acting antiviral introduction, suggesting reinfection has not affected elimination efforts among people with HIV in InCHEHC countries. The proportion of incident HCV cases due to reinfection was highest during periods of broad access to direct-acting antivirals, highlighting the importance of reducing ongoing risks and continuing testing in people at risk., Funding: Australian National Health and Medical Research Council., Competing Interests: Declaration of interests MK reports grants for investigator-initiated studies from ViiV Healthcare, AbbVie, and Gilead; consulting fees from ViiV Healthcare, AbbVie, and Gilead, all outside the submitted work; and is supported by a Tier I Canada Research Chair. AR reports support to his institution for advisory boards or travel grants from MSD, Gilead Sciences, and Pfizer, and an investigator initiated trial grant from Gilead Sciences; all remuneration to AR was paid to his home institution, and all remuneration was provided outside the submitted work. KL reports honoraria for advice or public speaking from Gilead, MSD, and ViiV Healthcare; support for attending meetings or travel expenses from Gilead and MSD; and a leadership or fiduciary role in other board, society, committee or advocacy groups, paid or unpaid, from Spikmm. FB reports grants from Gilead and honoraria from Gilead, ViiV Healthcare, and MSD. NKM received research grants from Gilead and the US National Institutes of Health unrelated to this work. TS reports consulting fees from Biogen for serving on advisory boards and scientific leadership committees. JSD reports investigator-initiated research funding to his institution from Gilead Sciences; investigator-initiated and company sponsored research funding to his institution from AbbVie; and consulting fees unrelated to this work to his institution from AbbVie. GVM reports grants or contracts from Gilead, AbbVie, ViiV Healthcare, and Janssen to her institution; payment or honoraria for lectures, presentations, speakers' bureaus, manuscript writing or educational events; and support for attending meetings or travel expenses from Gilead; and participation on a data safety monitoring board or advisory board for Gilead, ViiV Healthcare, and AstraZeneca. IJ reports payment or honoraria for lectures, presentations, speakers' bureaus, manuscript writing or educational events from Gilead Sciences, ViiV Healthcare, and GESIDA; and payment for expert testimony and support for attending meetings or travel expenses from Gilead Sciences. AB reports speakers fees from Gilead Sciences; and participation on a data safety monitoring board for Amsterdam University Medical Centers and an advisory board for ANRS Emerging Infectious Diseases. MvdV reports grants or contracts and consulting fees from Gilead, ViiV Healthcare, and MSD to his institution. MH reports investigator-initiated research grants from Gilead Sciences and AbbVie. MS reports investigator-initiated research grants from Gilead Sciences and AbbVie. M-BR reports funding from SIDACTION for the duration of her PhD. RG reports funding from Cepheid and SpeeDex towards the Australian Research Council Industrial Transformation Research Program Hub to Combat Antimicrobial Resistance grant (IH190100021). Cepheid has also contributed in-kind study equipment (cartridges, machines) to the project Scaling up infectious disease point-of-care testing for Indigenous people (RARUR000080) funded by the Medical Research Future Fund Rapid Applied Research Translation grant. RS-D, DKvS, CS, OL, MP, LW, JY, AS, and JB declare no competing interests., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Background: Among people living with HIV and hepatitis C virus (HCV), people who inject drugs (PWID) have historically experienced higher mortality rates. Direct-acting antivirals (DAA), which have led to a 90 % HCV cure rate independently of HIV co-infection, have improved mortality rates. However, DAA era mortality trends among PWID with HIV/HCV remain unknown. Using data from the International Collaboration on Hepatitis C Elimination in HIV Cohorts (InCHEHC), we compared pre/post-DAA availability mortality changes in three groups: PWID, men who have sex with men (MSM), and all other participants., Methods: We included InCHEHC participants with HIV/HCV followed between 2010 and 2019 in Canada, France, the Netherlands, Spain, and Switzerland. All-cause mortality hazard was compared in the three groups, using Cox proportional hazards regression models adjusted for sex, age, advanced fibrosis/cirrhosis, and pre/post DAA availability., Results: Of the 11,029 participants, 76 % were men, 46 % were PWID, baseline median age was 46 years (interquartile range [IQR] = 40;51), and median CD4 T-cell count was 490 cells/mm 3 (IQR = 327;689). Over the study period (median follow-up = 7.2 years (IQR = 3.7;10.0)), 6143 (56 %) participants received HCV treatment, 4880 (44 %) were cured, and 1322 participants died (mortality rate = 1.81/100 person-years (PY) [95 % confidence interval (CI)=1.72-1.91]). Overall, PWID had higher mortality rates than MSM (2.5/100 PY [95 % CI = 2.3-2.6] vs. 0.8/100 PY [95 % CI = 0.7-0.9], respectively). Unlike women with other transmission modes, those who injected drugs had a higher mortality hazard than men who did not inject drugs and men who were not MSM (adjusted Hazard-Ratio (aHR) [95 % CI] = 1.3[1.0-1.6]). Post-DAA availability, mortality decreased among MSM in the Netherlands, Spain, and Switzerland and increased among PWID in Canada (aHR [95 % CI] = 1.73 [1.15-2.61])., Conclusion: Post-DAA availability, all-cause mortality did not decrease in PWID. Determinants of cause-specific deaths (drug-related, HIV-related, or HCV-related) need to be identified to explain persistently high mortality among PWID in the DAA era., Competing Interests: Declaration of competing interest Juan Berenguer reports honoraria for advice and public speaking from ABBVIE, GILEAD, MSD, JANSSEN, and ViiV Healthcare, as well as grants from ABBVIE, GILEAD, MSD, and ViiV Healthcare. Marina Klein reports grants for investigator-initiated studies from ViiV Healthcare, AbbVie, and Gilead, and consulting fees from ViiV Healthcare, AbbVie, and Gilead, all outside the submitted work. Marina Klein is supported by a Tier I Canada Research Chair. Andri Rauch reports support to his institution for advisory boards and/or travel grants from MSD, Gilead Sciences, and Pfizer, and an investigator-initiated trial (IIT) grant from Gilead Sciences. All remuneration to Andri Rauch went to his home institution and not to Andri Rauch personally; furthermore this remuneration was provided outside the submitted work. Karine Lacombe reports honoraria for advice and public speaking from Abbvie, Gilead, MSD, Janssen and ViiH Healthcare., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Background: Microelimination of the hepatitis C virus (HCV) among men who have sex with men (MSM) could be complicated by continuous external introductions and the emergence of phylogenetic clusters harbouring clinically significant resistance-associated substitutions (RAS). To investigate international clustering and the prevalence and transmission of RAS, we aimed to analyse whole-genome HCV sequences from MSM with a recently acquired infection who participated in a large, international HCV treatment trial., Methods: For this whole-genome analysis, we obtained HCV sequences from 128 MSM who had acquired HCV within the past 12 months and were participating in the REACT trial. The participants from whom sequences were obtained were recruited at 24 sites in eight countries. We inferred maximum-likelihood phylogenies and identified transmission clusters for HCV genotypes separately. We constructed time-scaled phylogenies to estimate cluster introduction dates and used a Bayesian Skygrid approach to estimate the effective population size over the past 50 years. We calculated the prevalence of RAS and the extent of RAS transmission in the study population., Findings: The majority of recent HCV infections were part of international networks that arose in the late 1990s and early 2000s. Sequences obtained in the same country clustered frequently, and in 36% of subclusters since 2015 we found evidence of international transmission. European MSM were more likely than non-European MSM to be in a cluster (odds ratio 11·9 [95% CI 3·6-43·4], p<0·0001). The effective population size decreased rapidly since around 2015 in Europe. RAS associated with substantially diminished cure rates were infrequently detected and transmission of highly resistant viruses was not observed., Interpretation: Despite antiviral treatment becoming widely available, international transmission of HCV among MSM has still occurred over the past 8 years, which could complicate microelimination of the virus in this population. RAS-enriched clusters and widespread RAS transmission are currently not a threat to elimination goals. These findings support an international approach for HCV microelimination among MSM., Funding: National Institutes of Health and Dr. C.J. Vaillant Fonds., Competing Interests: Declaration of interests GM reports grants from Gilead Sciences and AbbVie, outside of the submitted work. SB reports grants from Gilead Sciences and personal fees for advisory board membership, lectures, and presentations from Gilead Sciences, all outside the submitted work. MvdV reports grants and personal fees from AbbVie, Gilead Sciences, Johnson & Johnson, MSD, and ViiV, outside the submitted work. JR reports personal fees from Gilead Sciences, Janssen, Merck, Theratechnologies, and ViiV, outside the submitted work. JF reports grants and personal fees from Gilead Sciences, Enanta, and AbbVie; personal fees from GSK, Arubutus, and Roche; and grants from Janssen and Eiger, all outside the submitted work. AR is a member of advisory boards of MSD and Gilead Sciences; has received travel grants from Gilead Sciences, Pfizer, and AbbVie; and has received an investigator-initiated trial grant from Gilead Sciences; all remuneration was to his home institution (Bern University Hospital, Bern, Switzerland) and not to AR personally. JB reports grants from the National Institutes of Health during the conduct of the study; personal fees from AbbVie; grants and personal fees from Gilead Sciences; and grants from the Canadian Institutes of Health Research, Fonds de Recherche—Québec, Substance Use and Abuse program, and Health Canada, outside the submitted work. MH reports grants from Gilead Sciences and AbbVie, outside the submitted work. PI reports grants and personal fees from Gilead Sciences and personal fees from AbbVie and ViiV, outside the submitted work. JG reports grants and personal fees from AbbVie, Gilead Sciences, Merck, and Cepheid; grants from Hologic and Indivior; payment or honoraria and travel support from AbbVie, Gilead Sciences, and Cepheid; receipt of testing equipment and cartridges from Cepheid; and receipt of testing reagents from Hologic; outside the submitted work. GJD reports grants, personal fees, and non-financial support from Gilead Sciences, AbbVie, and Merck and grants from Bristol-Myers Squibb, outside the submitted work. JS's institution (Amsterdam University Medical Centers, University of Amsterdam, Amsterdam, Netherlands) has received research support and consultancy fees from Gilead Sciences (NoCO grant) and a speaker's fee from Janssen Pharmaceuticals, outside the submitted work. CB reports honoraria for lectures and/or consultancies from AbbVie, Gilead Sciences, Janssen, MSD, and ViiV and funding from Dt. Leberstiftung, DZIF, Hector Stiftung, and NEAT ID. JK, SR, RS-D, MM, and TLA declare no competing interests., (Copyright © 2023 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4·0 license. Published by Elsevier Ltd.. All rights reserved.)

Background: Individuals with HIV and hepatitis C virus (HCV) who remain untreated with direct-acting antivirals can contribute to HCV transmission and HCV-related mortality. We aimed to compare rates of uptake of direct-acting antivirals following unrestricted access to this treatment in high-income countries and examine factors associated with remaining untreated., Methods: This multinational, prospective cohort study used data from the International Collaboration on Hepatitis C Elimination in HIV Cohorts (InCHEHC). We analysed data from nine observational cohorts participating in the InCHEHC, including data from six high-income countries (Australia, Canada, France, the Netherlands, Spain, and Switzerland). We included individuals aged 18 years and older, with HIV and HCV (ie, HCV-RNA positive without evidence of spontaneous clearance) during unrestricted access to interferon-free direct-acting antiviral treatment in each country. We calculated the cumulative proportion of participants who remained untreated with direct-acting antivirals, with follow-up starting after the date of unrestricted access or cohort inclusion, whichever occurred most recently. Factors associated with the commencement rate of direct-acting antiviral treatment were assessed using competing-risks regression with the Fine-Gray method., Findings: The date of unrestricted access to direct-acting antiviral treatment for people with HIV ranged from Nov 1, 2014, in France to Nov 1, 2017, in Switzerland. We included 4552 individuals with HIV-HCV, mainly men who have sex with men (MSM; n=2156 [47%]) and people who inject or have injected drugs (n=1453 [32%]). 1365 (30%) of 4552 participants remained untreated with direct-acting antivirals. For individuals treated with direct-acting antivirals, median time from start of follow-up to treatment was 5 months (IQR 2-12). For individuals who were not treated with direct-acting antivirals, median follow-up was 22 months (8-30). Being linked to care in Australia, France, or the Netherlands, on antiretroviral therapy, having undetectable HIV RNA, and shorter duration since first positive HCV test were independently associated with higher commencement rate of direct-acting antiviral treatment. Compared with MSM, male heterosexuals and females with unknown or other routes of HIV transmission (ie, neither injection drug use nor heterosexual transmission) had lower rates of commencement., Interpretation: Despite unrestricted access, almost a third of individuals with HIV-HCV remained untreated with direct-acting antivirals during follow-up, with variation in commencement rate of HCV treatment between countries and key populations. Increased efforts are required to reach the remaining individuals with HIV who are HCV-viraemic to achieve HIV-HCV micro-elimination., Funding: None., Competing Interests: Declaration of interests CJI has received research funding from Gilead, unrelated to this work. MS has received investigator-initiated research funding from Gilead Sciences and AbbVie and consultant fees from Gilead Sciences for activities unrelated to this work. JB has received grants from Gilead, MSD, and ViiV Healthcare; and honoraria for advice or public speaking from Gilead, MSD, Janssen, and ViiV Healthcare. MBK reports grants for investigator-initiated studies from ViiV Healthcare, AbbVie, and Gilead, and consulting fees from ViiV Healthcare, AbbVie, and Gilead, all outside the submitted work. MBK is supported by a Tier I Canada Research Chair. AR reports support to his institution for advisory boards or travel grants from MSD, Gilead Sciences, Pfizer, and AbbVie, and an investigator-initiated trial grant from Gilead Sciences. All remuneration went to his home institution and not to AR personally, and all remuneration was provided outside the submitted work. JS's institution has received research support and consultancy fees from Gilead, and a speaker's fee from Janssen Pharmaceuticals, independent from the submitted work. JSD receives funding from Gilead Sciences and AbbVie, unrelated to this work. MH receives funding from Gilead Sciences and AbbVie unrelated to this work. MvdV reports honoraria or research grants from Gilead, MSD, and ViiV Healthcare, all paid to his institution and outside the submitted work. KL has received research support from MSD unrelated to this work. All other authors report no competing interests., (Copyright © 2023 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY-NC-ND 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

Background: Hepatitis C virus (HCV) infection has been reported among gay, bisexual, and other men who have sex with men (GBM) globally including GBM with human immunodeficiency virus (HIV) and HIV-negative GBM, particularly those using HIV preexposure prophylaxis (PrEP). In Australia, HCV direct-acting antiviral treatment (DAA) was government-funded from 2016. Large implementation studies of PrEP also began in 2016. We examined HCV incidence among GBM to assess whether HCV incidence has changed since 2015., Methods: Data were drawn from the Australian Collaboration for Coordinated Enhanced Sentinel Surveillance. We included GBM who tested HCV antibody negative at their first test and had ≥1 subsequent test. Generalized linear modeling (Poisson distribution) was used to examine HCV incidence from 2009 to 2019 stratified by HIV status, and among HIV-negative GBM prescribed PrEP from 2016 to 2019., Results: Among 6744 GBM with HIV, HCV incidence was 1.03 per 100 person-years (PY). Incidence declined by 78% in 2019 compared to 2015 (incidence rate ratio [IRR], 0.22 [95% confidence interval {CI}: .09-.55]). Among 20 590 HIV-negative GBM, HCV incidence was 0.20/100 PY, with no significant change over time. Among 11 661 HIV-negative GBM prescribed PrEP, HCV incidence was 0.29/100 PY. Compared to 2016, incidence among GBM prescribed PrEP declined by 80% in 2019 (IRR, 0.20 [95% CI: .06-.64])., Conclusions: HCV incidence among GBM living with HIV declined following DAA availability. There was no observed change in HCV incidence among HIV-negative GBM overall. Among GBM prescribed PrEP, incidence declined since the early years of PrEP implementation in Australia. Australia is on track to eliminate HCV among GBM before global 2030 targets., (© The Author(s) 2021. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.)

Background: This study aimed to investigate the potential influence of venue-based networks on HCV transmission in HIV-positive gay and bisexual men (GBM)., Methods: This was a prospectively recruited cohort of HIV-infected GBM with recently-acquired HCV infection resident in Melbourne and Sydney. Clinical and demographic data were collected together with blood samples for HCV sequencing. Phylogenies were inferred and clusters of individuals infected with HCV with genetic sequence homology were identified. Venues used for sourcing sexual partners were identified; sourcing partners from the same venue was considered a potential social link. Using the Jaccard similarity coefficient, associations were identified between the network of sites where men sourced sex partners and transmission relationships as defined by phylogenetic clustering., Results: Forty individuals were recruited, of whom 62.5% were considered to have sexually- and 37.5% IDU-acquired HCV. Venue use was consistent with men being members of a more sexually adventurous gay community subculture. Six phylogenetically-determined pairs or clusters were identified, comprising fifteen (15/28, 53.6%) individuals. Participants belonging to phylogenetic clusters were observed within the same networks. There was a significant correlation between the network and phylogenetic clustering when both cities were considered simultaneously (p = 0.005), raising the possibility that social connections may be important for HCV transmissions., Conclusions: Venue-based network elicitation is a promising approach for elucidating HCV transmissions amongst HIV-infected GBM. Public health approaches targeting individuals and venues prominent within networks may reduce onward HCV transmission., Competing Interests: The authors have declared that no competing interests exist.