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.

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.

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.

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.

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.

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.

The cost-effectiveness of universal hepatitis B screening for reaching WHO diagnosis targets in Australia by 2030.

OBJECTIVES: To assess the impact on diagnosis targets, cost, and cost-effectiveness of universal hepatitis B screening in Australia. DESIGN: Markov model simulation of disease and care cascade progression for people with chronic hepatitis B in Australia. SETTING: Three scenarios were compared: 1. no change to current hepatitis B virus (HBV) testing practice; 2. universal screening strategy, with the aim of achieving the WHO diagnosis target by 2030 (90% of people with chronic hepatitis B diagnosed), based on opportunistic (general practitioner-initiated) screening for HBsAg; 3. universal screening strategy, and also ensuring that 50% of people with chronic hepatitis B are receiving appropriate clinical management by 2030. MAIN OUTCOME MEASURES: Projected care cascade for people with chronic hepatitis B, cumulative number of HBV-related deaths, intervention costs, and health utility (quality-adjusted life-years [QALYs] gained during 2020-2030). An incremental cost-effectiveness ratio (ICER) threshold (v scenario 1) of $50 000 per QALY gained was applied. RESULTS: Compared with scenario 1, 80 HBV-related deaths (interquartile range [IQR], 41-127 deaths) were averted during 2020-2030 in scenario 2, 315 HBV-related deaths (IQR, 211-454 deaths) in scenario 3. Scenario 2 cost $84 million (IQR, $41-106 million) more than scenario 1 during 2020-2030 (+8%), yielding an ICER of $104 921 (IQR, $49 587-107 952) per QALY gained. Scenario 3 cost $263 million (IQR, $214-316 million) more than scenario 1 during 2020-2030 (+24%), yielding an ICER of $47 341 (IQR, $32 643-58 200) per QALY gained. Scenario 3 remained cost-effective if the test positivity rate was higher than 0.35% or the additional costs per person tested did not exceed $4.02. CONCLUSIONS: Universal screening for hepatitis B will be cost-effective only if the cost of testing is kept low and people receive appropriate clinical management.

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.

Eliminating hepatitis C in Australia: a novel model of hepatitis C testing and treatment for people who inject drugs at a medically supervised injecting facility.

OBJECTIVE: To evaluate the feasibility of testing and treating people who inject drugs at a supervised injecting facility for hepatitis C virus (HCV) infection. DESIGN: Retrospective cohort study. SETTING, PARTICIPANTS: People who inject drugs who attended the Melbourne supervised injecting facility, 30 June 2018 - 30 June 2020. MAIN OUTCOME MEASURES: Proportion of people tested for hepatitis C; proportions of people positive for anti-HCV antibody and HCV RNA, and of eligible people prescribed direct-acting antiviral (DAA) treatment; sustained virological response twelve weeks or more after treatment completion. RESULTS: Of 4649 people who attended the supervised injecting facility during 2018-20, 321 were tested for hepatitis C (7%); 279 were anti-HCV antibody-positive (87%), of whom 143 (51%) were also HCV RNA-positive. Sixty-four of 321 had previously been treated for hepatitis C (20%), 21 had clinically identified cirrhosis (7%), eight had hepatitis B infections (2%), and four had human immunodeficiency virus infections (1%). In multivariate analyses, people tested for hepatitis C were more likely than untested clients to report psychiatric illness (adjusted odds ratio [aOR], 9.65; 95% confidence interval [CI], 7.26-12.8), not have a fixed address (aOR, 1.59; 95% CI, 1.18-2.14), and to report significant alcohol use (aOR, 1.57; 95% CI, 1.06-2.32). The median number of injecting facility visits was larger for those tested for hepatitis C (101; interquartile range [IQR], 31-236) than for those not tested (20; IQR, 3-90). DAA treatment was prescribed for 126 of 143 HCV RNA-positive clients (88%); 41 of 54 with complete follow-up data were cured (76%). CONCLUSIONS: People who attend supervised injecting facilities can be tested and treated for hepatitis C on site. Models that provide streamlined, convenient hepatitis C care promote engagement with treatment in a group in which the prevalence of hepatitis C is high.

The Incidence of Hepatitis C Among Gay, Bisexual, and Other Men Who Have Sex With Men in Australia, 2009-2019.

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.