Syphilis testing, incidence, and reinfection among gay and bisexual men in Australia over a decade spanning HIV PrEP implementation: an analysis of surveillance data from 2012 to 2022.

Background: Gay and bisexual men (GBM) remain overrepresented among syphilis diagnoses in Australia and globally. The extent to which changes in sexual networks associated with HIV pre-exposure prophylaxis (PrEP) and treatment as prevention (TasP) may have influenced syphilis transmission among GBM at the population-level is poorly understood. We describe trends in syphilis testing and incidence among GBM in Australia over eleven years spanning widespread uptake of HIV PrEP and TasP. Methods: We analysed linked clinical data from GBM aged 16 years or older across a sentinel surveillance network in Australia from January 1, 2012, to December 31, 2022. Individuals with at least two clinic visits and with at least two syphilis tests during the observations period were included in testing and incidence analyses, respectively. Annual rates of testing and infectious syphilis incidence from 2012 to 2022 were disaggregated by HIV status and PrEP use (record of PrEP prescription; retrospectively categorised as ever or never-PrEP user). Cox regression explored associations between demographics, PrEP use and history of bacterial sexually transmissible infections (STIs) and infectious syphilis diagnosis. Findings: Among 129,278 GBM (mean age, 34.6 years [SD, 12.2]) included in testing rate analyses, 7.4% were living with HIV at entry and 31.1% were prescribed PrEP at least once during the study period. Overall syphilis testing rate was 114.0/100 person-years (py) and highest among GBM with HIV (168.4/100 py). Syphilis testing increased from 72.8/100 py to 151.8/100 py; driven largely by increases among ever-PrEP users. Among 94,710 GBM included in incidence analyses, there were 14,710 syphilis infections diagnosed over 451,560 person-years (incidence rate = 3.3/100 py). Syphilis incidence was highest among GBM with HIV (6.5/100 py), followed by ever-PrEP users (3.5/100 py) and never-PrEP users (1.4/100 py). From 2012 to 2022, syphilis incidence increased among ever-PrEP users from 1.3/100 py to 5.1/100 py, and fluctuated between 5.4/100 py and 6.6/100 py among GBM with HIV. In multivariable Cox regression, previous syphilis diagnosis (adjusted hazard ratio [aHR] = 1.98, 95% CI = 1.83-2.14), living with HIV (aHR = 1.83, 95% CI = 1.12-1.25) and recent (past 12 m) prescription of PrEP (aHR = 1.78, 95% CI = 1.61-1.97) were associated with syphilis diagnosis. Interpretation: Syphilis trends between GBM with HIV and GBM with evidence of PrEP use have converged over the past decade in Australia. Our findings recommend targeting emergent syphilis control strategies (e.g. doxycycline post-exposure prophylaxis) to GBM with prior syphilis diagnoses, using HIV PrEP or who are living with HIV. Funding: Australian Department of Health and Aged Care, National Health and Medical Research Council.

Improving Hepatocellular Carcinoma Surveillance Outcomes in Patients with Cirrhosis after Hepatitis C Cure: A Modelling Study.

BACKGROUND & AIMS: Hepatocellular carcinoma (HCC) presents a significant global health challenge, particularly among individuals with liver cirrhosis, with hepatitis C (HCV) a major cause. In people with HCV-related cirrhosis, an increased risk of HCC remains after cure. HCC surveillance with six monthly ultrasounds has been shown to improve survival. However, adherence to biannual screening is currently suboptimal. This study aimed to evaluate the effect of increased HCC surveillance uptake and improved ultrasound sensitivity on mortality among people with HCV-related cirrhosis post HCV cure. METHODS: This study utilized mathematical modelling to assess HCC progression, surveillance, diagnosis, and treatment among individuals with cirrhosis who had successfully been treated for HCV. The deterministic compartmental model incorporated Barcelona Clinic Liver Cancer (BCLC) stages to simulate disease progression and diagnosis probabilities in 100 people with cirrhosis who had successfully been treated for hepatitis C over 10 years. Four interventions were modelled to assess their potential for improving life expectancy: realistic improvements to surveillance adherence, optimistic improvements to surveillance adherence, diagnosis sensitivity enhancements, and improved treatment efficacy Results: Realistic adherence improvements resulted in 9.8 (95% CI 7.9, 11.6) life years gained per cohort of 100 over a 10-year intervention period; 17.2 (13.9, 20.3) life years were achieved in optimistic adherence improvements. Diagnosis sensitivity improvements led to a 7.0 (3.6, 13.8) year gain in life years, and treatment improvements improved life years by 9.0 (7.5, 10.3) years. CONCLUSIONS: Regular HCC ultrasound surveillance remains crucial to reduce mortality among people with cured hepatitis C and cirrhosis. Our study highlights that even minor enhancements to adherence to ultrasound surveillance can significantly boost life expectancy across populations more effectively than strategies that increase surveillance sensitivity or treatment efficacy.

Same-visit hepatitis C testing and treatment to accelerate cure among people who inject drugs (the QuickStart Study): a cluster randomised cross-over trial protocol.

INTRODUCTION: Despite universal access to government-funded direct-acting antivirals (DAAs) in 2016, the rate of hepatitis C treatment uptake in Australia has declined substantially. Most hepatitis C is related to injecting drug use; reducing the hepatitis C burden among people who inject drugs (PWID) is, therefore, paramount to reach hepatitis C elimination targets. Increasing DAA uptake by PWID is important for interrupting transmission and reducing incidence, as well as reducing morbidity and mortality and improving quality of life of PWID and meeting Australia's hepatitis C elimination targets. METHODS AND ANALYSIS: A cluster randomised cross-over trial will be conducted with three intervention arms and a control arm. Arm A will receive rapid hepatitis C virus (HCV) antibody testing; arm B will receive rapid HCV antibody and rapid RNA testing; arm C will receive rapid HCV antibody testing and same-day treatment initiation for HCV antibody-positive participants; the control arm will receive standard of care. The primary outcomes will be (a) the proportion of participants with HCV commencing treatment and (b) the proportion of participants with HCV achieving cure. Analyses will be conducted on an intention-to-treat basis with mixed-effects logistic regression models. ETHICS AND DISSEMINATION: The study has been approved by the Alfred Ethics Committee (number HREC/64731/Alfred-2020-217547). Each participant will provide written informed consent. Reportable adverse events will be reported to the reviewing ethics committee. The findings will be presented at scientific conferences and published in peer-reviewed journals. TRIAL REGISTRATION NUMBER: NCT05016609. TRIAL PROGRESSION: The study commenced recruitment on 9 March 2022 and is expected to complete recruitment in December 2024.

Annual hepatitis C testing and positive tests among gay and bisexual men in Australia from 2016 to 2022: a serial cross-sectional analysis of sentinel surveillance data.

OBJECTIVE: Guidelines recommend annual hepatitis C virus (HCV) testing for gay and bisexual men (GBM) with HIV and GBM prescribed HIV pre-exposure prophylaxis (PrEP). However, there is a limited understanding of HCV testing among GBM. We aimed to examine trends in HCV testing and positivity from 2016 to 2022. METHODS: Using sentinel surveillance data, we examined the proportion of GBM with at least one test and the proportion with a positive test in each year for HCV antibody testing among GBM with no previous HCV positive test, HCV RNA testing among GBM with a positive antibody test but no previous positive RNA test (naïve RNA testing), and HCV RNA testing among people who had a previous RNA positive test and a subsequent negative test (RNA follow-up testing). Trends were examined using logistic regression from 2016 to 2019 and 2020 to 2022. RESULTS: Among GBM with HIV, from 2016 to 2019 antibody testing was stable averaging 55% tested annually. Declines were observed for both naïve HCV RNA testing (75.4%-41.4%: p<0.001) and follow-up HCV RNA testing (70.1%-44.5%: p<0.001). Test positivity declined for HCV antibody tests (2.0%-1.3%: p=0.001), HCV RNA naïve tests (75.4%-41.4%: p<0.001) and HCV RNA follow-up tests (11.3%-3.3%: p=0.001). There were minimal or no significant trends from 2020 to 2022.Among GBM prescribed PrEP, antibody testing declined from 2016 to 2019 (79.4%-69.4%: p<0.001) and was stable from 2020 to 2022. Naïve and follow-up HCV RNA testing was stable with an average of 55% and 60% tested each year, respectively. From 2016-2019, the proportion positive from HCV RNA naïve tests declined (44.1%-27.5%: p<0.046) with no significant change thereafter. Positive follow-up HCV RNA tests fluctuated with no or one new positive test among this group in most years. CONCLUSION: The proportion of GBM with positive HCV tests has declined, however a substantial proportion are not tested annually. A renewed focus on HCV testing, and treatment where required, is warranted to achieve HCV elimination among GBM in Australia.

Risk of Primary Incident Hepatitis C Infection Following Bacterial Sexually Transmissible Infections Among Gay and Bisexual Men in Australia From 2016 to 2020.

Background: In Australia, the incidence of hepatitis C virus (HCV) has declined among gay and bisexual men (GBM) with human immunodeficiency virus (HIV) since 2015 and is low among GBM using HIV preexposure prophylaxis (PrEP). However, ongoing HCV testing and treatment remains necessary to sustain this. To assess the potential utility of sexually transmissible infections (STIs) to inform HCV testing among GBM with HIV and GBM using PrEP, we examined the association between bacterial STI diagnoses and subsequent primary HCV infection. Methods: Data were from a national network of 46 clinics participating in the Australian Collaboration for Coordinated Enhanced Sentinel Surveillance. GBM included had ≥1 HCV antibody negative test result and ≥1 subsequent HCV antibody and/or RNA test. Discrete time survival analysis was used to estimate the association between a positive syphilis, rectal chlamydia, and rectal gonorrhea diagnosis in the previous 2 years and a primary HCV diagnosis, defined as a positive HCV antibody or RNA test result. Results: Among 6529 GBM with HIV, 92 (1.4%) had an incident HCV infection. A prior positive syphilis diagnosis was associated with an incident HCV diagnosis (adjusted hazard ratio, 1.99 [95% confidence interval, 1.11-3.58]). Among 13 061 GBM prescribed PrEP, 48 (0.4%) had an incident HCV diagnosis. Prior rectal chlamydia (adjusted hazard ratio, 2.75 [95% confidence interval, 1.42-5.32]) and rectal gonorrhea (2.54 [1.28-5.05]) diagnoses were associated with incident HCV. Conclusions: Diagnoses of bacterial STIs in the past 2 years was associated with HCV incidence. These findings suggest that STIs might be useful for informing HCV testing decisions and guidelines for GBM with HIV and GBM using PrEP.

Viral hepatitis testing and treatment in community pharmacies: a systematic review and meta-analysis.

Background: The World Health Organization seeks to eliminate viral hepatitis as a public health threat by 2030. This review and meta-analysis aims to evaluate the effectiveness of programs for hepatitis B and C testing and treatment in community pharmacies. Methods: Medline, Embase, Cochrane CENTRAL, and Global Health were searched from database inception until 12 November 2023. Comparative and single arm intervention studies were eligible for inclusion if they assessed delivery of any of the following interventions for hepatitis B or C in pharmacies: (1) pre-testing risk assessment, (2) testing, (3) pre-treatment assessment or (4) treatment. Primary outcomes were proportions testing positive and reaching each stage in the cascade. Random effects meta-analysis was used to estimate pooled proportions stratified by recruitment strategy and setting where possible; other results were synthesised narratively. This study was pre-registered (PROSPERO: CRD42022324218). Findings: Twenty-seven studies (4 comparative, 23 single arm) were included, of which 26 reported hepatitis C outcomes and four reported hepatitis B outcomes. History of injecting drug use was the most identified risk factor from pre-testing risk assessments. The pooled proportion hepatitis C antibody positive from of 19 studies testing 5096 participants was 16.6% (95% CI 11.0%-23.0%; heterogeneity I2 = 96.6%). The pooled proportion antibody positive was significantly higher when testing targeted people with specified risk factors (32.5%, 95% CI 24.8%-40.6%; heterogeneity I2 = 82.4%) compared with non-targeted or other recruitment methods 4.0% (95% CI 2.1%-6.5%; heterogeneity I2 = 83.5%). Meta-analysis of 14 studies with 813 participants eligible for pre-treatment assessment showed pooled attendance rates were significantly higher in pharmacies (92.7%, 95% CI 79.1%-99.9%; heterogeneity I2 = 72.4%) compared with referral to non-pharmacy settings (53.5%, 95% CI 36.5%-70.1%; heterogeneity I2 = 92.3%). The pooled proportion initiating treatment was 85.6% (95% CI 74.8%-94.3%; heterogeneity I2 = 75.1%). This did not differ significantly between pharmacy and non-pharmacy settings. Interpretation: These findings add pharmacies to the growing evidence supporting community-based testing and treatment for hepatitis C. Few comparative studies and high degrees of statistical heterogeneity were important limitations. Hepatitis B care in pharmacies presents an opportunity for future research. Funding: None.

Injecting drug use and hepatitis C virus infection independently increase biomarkers of inflammatory disease risk which are incompletely restored by curative direct-acting antiviral therapy.

Background: Hepatitis C virus (HCV) infections are more prevalent in people who inject drugs (PWID) who often experience additional health risks. HCV induces inflammation and immune alterations that contribute to hepatic and non-hepatic morbidities. It remains unclear whether curative direct acting antiviral (DAA) therapy completely reverses immune alterations in PWID. Methods: Plasma biomarkers of immune activation associated with chronic disease risk were measured in HCV-seronegative (n=24) and HCV RNA+ (n=32) PWID at baseline and longitudinally after DAA therapy. Adjusted generalised estimating equations were used to assess longitudinal changes in biomarker levels. Comparisons between community controls (n=29) and HCV-seronegative PWID were made using adjusted multiple regression modelling. Results: HCV-seronegative PWID exhibited significantly increased levels of inflammatory biomarkers including soluble (s) TNF-RII, IL-6, sCD14 and sCD163 and the diabetes index HbA1c as compared to community controls. CXCL10, sTNF-RII, vascular cell adhesion molecule-1 and lipopolysaccharide binding protein (LBP) were additionally elevated in PWID with viremic HCV infection as compared to HCV- PWID. Whilst curative DAA therapy reversed some biomarkers, others including LBP and sTNF-RII remained elevated 48 weeks after HCV cure. Conclusion: Elevated levels of inflammatory and chronic disease biomarkers in PWID suggest an increased risk of chronic morbidities such as diabetes and cardiovascular disease. HCV infection in PWID poses an additional disease burden, amplified by the incomplete reversal of immune dysfunction following DAA therapy. These findings highlight the need for heightened clinical surveillance of PWID for chronic inflammatory diseases, particularly those with a history of HCV infection.

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.

Hepatitis C virus reinfection incidence among gay and bisexual men with HIV in Australia from 2016 to 2020.

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.

All-cause mortality before and after DAA availability among people living with HIV and HCV: An international comparison between 2010 and 2019.

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/mm3 (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.

Determining reinfection rates by hepatitis C testing interval among key populations: A systematic review and meta-analysis.

BACKGROUND & AIMS: Detecting hepatitis C virus (HCV) reinfection among key populations helps prevent ongoing transmission. This systematic review aims to determine the association between different testing intervals during post-SVR follow-up on the detection of HCV reinfection among highest risk populations. METHODS: We searched electronic databases between January 2014 and February 2023 for studies that tested individuals at risk for HCV reinfection at discrete testing intervals and reported HCV reinfection incidence among key populations. Pooled estimates of reinfection incidence were calculated by population and testing frequency using random-effects meta-analysis. RESULTS: Forty-one single-armed observational studies (9453 individuals) were included. Thirty-eight studies (8931 individuals) reported HCV reinfection incidence rate and were included in meta-analyses. The overall pooled estimate of HCV reinfection incidence rate was 4.13 per 100 per person-years (py) (95% confidence interval [CI]: 3.45-4.81). The pooled incidence estimate among people who inject drugs (PWID) was 2.84 per 100 py (95% CI: 2.19-3.50), among men who have sex with men (MSM) 7.37 per 100 py (95% CI: 5.09-9.65) and among people in custodial settings 7.23 per 100 py (95% CI: 2.13-16.59). The pooled incidence estimate for studies reporting a testing interval of ≤6 months (4.26 per 100 py; 95% CI: 2.86-5.65) was higher than studies reporting testing intervals >6 months (5.19 per 100 py; 95% CI: 3.92-6.46). CONCLUSIONS: HCV reinfection incidence was highest in studies of MSM and did not appear to change with retesting interval. Shorter testing intervals are likely to identify more reinfections, help prevent onward transmission where treatment is available and enable progress towards global HCV elimination, but additional comparative studies are required.

Connecting patients notified with hepatitis C to treatment (CONNECT Study): A randomized controlled trial of active case management by a health department to support primary care practitioners.

BACKGROUND: Despite subsidised access to direct-acting antivirals (DAAs), hepatitis C (HCV) treatment uptake in Australia is declining. Interventions are needed to link people living with HCV to care and treatment. We implemented and measured effectiveness of a state-wide, health department-led, enhanced case management through the primary care practitioner for all HCV notifications, aiming to encourage and support treatment commencement. METHODS: A randomised controlled trial compared enhanced case management, delivered by the health department to diagnosing clinicians, with standard of care using notifiable disease systems in Tasmania, Australia (2020-21). The intervention involved a nurse specialist contacting and providing support by telephone to primary care practitioners making an HCV notification. The primary outcome was the proportion of cases notified with chronic hepatitis C who commenced treatment within 12 weeks of notification. We allowed a 12-week extended follow-up period at the end of the study for participants with no outcomes. RESULTS: Eighty-five primary care practitioners randomised to the intervention and 86 to standard of care arms notified 111 and 115 HCV cases, respectively. The proportion of cases notified with chronic hepatitis (HCV RNA detected) commencing treatment within 12 weeks was similar between study arms (41% vs 33%; p=0·51) and after extended study follow-up (65% vs 48%; p=0·18). RNA test completion was higher in the intervention than in standard of care arm (89% vs. 78%; p=0·03), while completing pre-treatment workup for chronic patients (65% vs. 64%; p=0·93) was similar. CONCLUSION: This was the first prospective randomised study of the utility of immediate HCV notification follow-up of primary care practitioners to enhance treatment uptake using disease notification surveillance data. We demonstrated improvement in HCV RNA testing and trend toward better engagement in care, but no significant increase in treatment uptake.

Identifying the Most Effective Recruitment Strategy Using Financial Reimbursements for a Web-Based Peer Network Study With Young People Aged 16-18 Years: Protocol for a Randomized Controlled Trial.

BACKGROUND: Peers are an important determinant of health and well-being during late adolescence; however, there is limited quantitative research examining peer influence. Previous peer network research with adolescents faced methodological limitations and difficulties recruiting young people. OBJECTIVE: This study aims to determine whether a web-based peer network survey is effective at recruiting adolescent peer networks by comparing 2 strategies for reimbursement. METHODS: This study will use a 2-group randomized trial design to test the effectiveness of reimbursements for peer referral in a web-based cross-sectional peer network survey. Young people aged 16-18 years recruited through Instagram, Snapchat, and a survey panel will be randomized to receive either scaled group reimbursement (the experimental group) or fixed individual reimbursement (the control group). All participants will receive a reimbursement of Aus $5 (US $3.70) for their own survey completion. In the experimental group (scaled group reimbursement), all participants within a peer network will receive an additional Aus $5 (US $3.70) voucher for each referred participant who completes the study, up to a maximum total value of Aus $30 (US $22.20) per participant. In the control group (fixed individual reimbursement), participants will only be reimbursed for their own survey completion. Participants' peer networks are assessed during the survey by asking about their close friends. A unique survey link will be generated to share with the participant's nominated friends for the recruitment of secondary participants. Outcomes are the proportion of a participant's peer network and the number of referred peers who complete the survey. The required sample size is 306 primary participants. Using a multilevel logistic regression model, we will assess the effect of the reimbursement intervention on the proportion of primary participants' close friends who complete the survey. The secondary aim is to determine participant characteristics that are associated with successfully recruiting close friends. Young people aged 16-18 years were involved in the development of the study design through focus groups and interviews (n=26). RESULTS: Participant recruitment commenced in 2022. CONCLUSIONS: A longitudinal web-based social network study could provide important data on how social networks and their influence change over time. This trial aims to determine whether scaled group reimbursement can increase the number of peers referred. The outcomes of this trial will improve the recruitment of young people to web-based network studies of sensitive health issues. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/44813.

Incidence and Prevalence of Hepatitis C Virus Among HIV-Negative Gay and Bisexual Men Using HIV Pre-exposure Prophylaxis (PrEP): A Systematic Review and Meta-analysis.

Background: Gay and bisexual men using HIV pre-exposure prophylaxis (PrEP) are at increased risk for sexually transmissible infections. Hepatitis C virus (HCV) risk among PrEP users is less clear. We explored HCV prevalence and incidence among cohorts of gay and bisexual men using PrEP and sources of heterogeneity across studies. Methods: This was a systematic review and meta-analysis of open-label PrEP studies to April 2022 reporting HCV prevalence at baseline or incidence during follow-up among gay and bisexual men using PrEP. Pooled prevalence and incidence estimates were calculated using random-effects meta-analysis, and subgroup analyses were performed by study- and country-level characteristics, including availability of HCV direct-acting antiviral (DAA) therapy at time of study. Results: Twenty-four studies from 9 countries were included, with a total sample of 24 733 gay and bisexual men. Pooled HCV antibody baseline prevalence was 0.97% (95% CI, 0.63%-1.31%), and pooled HCV RNA baseline prevalence was 0.38% (95% CI, 0.19%-0.56%). Among 19 studies reporting HCV incidence, incidence ranged from 0.0 to 2.93/100 person-years (py); the pooled estimate was 0.83/100py (95% CI, 0.55-1.11). HCV incidence was higher in 12 studies that began follow-up before broad DAA availability (1.27/100py) than in 8 studies that began follow-up after broad DAA availability (0.34/100py) and higher in studies in Europe compared with North America and Australia. Conclusions: Early reports of high HCV incidence among PrEP-using cohorts likely reflect enrollment of individuals based on specific risk-based eligibility criteria for smaller studies and enrollment before DAA scale-up. In contexts where both DAAs and PrEP have been implemented at scale, studies report lower HCV incidence. PrEP-specific HCV testing guidelines should be guided by local epidemiology.

Pathway to global elimination of hepatitis B: HBV cure is just the first step.

Hepatitis B (HBV) is a major cause of global morbidity and mortality, and the leading cause of liver cancer worldwide. Significant advances have recently been made toward the development of a finite HBV treatment that achieves permanent loss of HBsAg and HBV DNA (so-called "HBV cure"), which could provide the means to eliminate HBV as a public health threat. However, the HBV cure is just one step toward achieving WHO HBV elimination targets by 2030, and much work must be done now to prepare for the successful implementation of the HBV cure. In this review, we describe the required steps to rapidly scale-up future HBV cure equitably. We present key actions required for successful HBV cure implementation, integrated within the World Health Organization (WHO) Global Health Sector Strategy (GHSS) 2022-2030 framework. Finally, we highlight what can be done now to progress toward the 2030 HBV elimination targets using available tools to ensure that we are preparing, but not waiting, for the cure.

Time-to-hepatitis C treatment initiation among people who inject drugs in Melbourne, Australia.

This study aims to understand the time-to-treatment initiation pre and post DAA access to inform strategies to improve HCV care. The data for our study were derived from the SuperMIX cohort study of people who inject drugs in Melbourne, Australia. Time-to-event analysis using Weibull accelerated failure time was performed for data collected between 2009 and 2021, among a cohort of HCV-positive participants. Among 223 participants who tested positive for active hepatitis C infection, 102 people (45.7%) reported treatment initiation, with a median time-to-treatment of 7 years. However, the median time-to-treatment reduced to 2.3 years for those tested positive after 2016. The study found that treatment with Opioid Agonist Therapy (TR 0.7, 95% CI 0.6-0.9), engagement with health or social services (TR 0.7, 95% CI 0.6-0.9), and having a first positive HCV RNA test after March 2016 (TR 0.3, 95% CI 0.2-0.3) were associated with a reduced time-to-treatment initiation. The study highlights the need for strategies to improve engagement with health services, including drug treatment services into routine HCV care to achieve timely treatment.

Leave No-One Behind: A Retrospective Study of Hepatitis C Testing and Linkage to Care for Hospital Inpatients.

Hospital admissions are a missed opportunity to engage people living with hepatitis C virus (HCV) into care. This study aimed to describe the proportion of hospital inpatients and emergency department (ED) patients identified with hepatitis C who were subsequently linked to care and treatment at a metropolitan health service in Melbourne, Australia. Data were collected retrospectively from hospital databases (admissions, notifiable diseases, and pharmacy) for all adults admitted or attending the ED with separation coding indicating hepatitis C infection from March 2016 to March 2019. There were 2149 patients with at least one separation with hepatitis C coding. 15.4% (331/2149) had a documented antibody test, 4.6% (99/2149) had a documented RNA test, and 8.3% (179/2149) had a DAA prescription dispensed by hospital pharmacy. Antibody positivity was 95.2% (315/331) and RNA (when completed) was detected in 37.4% (37/99). Hepatitis specialist units had the highest rate of hepatitis C coded separations and RNA testing (39/88; 44.3%), mental health had the highest rate of antibody testing (70/276; 25.4%). Emergency had the lowest rate of antibody testing (101/1075; 13.7%) and the third highest rate of RNA testing (32/94; 34.1%), but the highest rate of RNA detected (15/32; 46.9%). This study highlights key steps to improve the care cascade. Simplified diagnostic pathways, expansion of hepatitis C care services, and clear in-hospital pathways to link patients to care would be beneficial in this setting. To scale up hepatitis C testing and treatment as part of national elimination strategies, hospital systems need to target interventions to their local data.