Evaluation of the hepatitis C cascade of care among people living with HIV in New South Wales, Australia: A data linkage study.

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.

Opportunities to Enhance Linkage to Hepatitis C Care Among Hospitalized People With Recent Drug Dependence in New South Wales, Australia: A Population-based Linkage Study.

BACKGROUND: People who inject drugs are at greater risk of hepatitis C virus (HCV) infection and hospitalization, yet admissions are not utilized for HCV treatment initiation. We aimed to assess the extent to which people with HCV notification, including those with evidence of recent drug dependence, are hospitalized while eligible for direct-acting antiviral (DAA) therapy, and treatment uptake according to hospitalization in the DAA era. METHODS: We conducted a longitudinal, population-based cohort study of people living with HCV in the DAA era (March 2016-December 2018) through analysis of linked databases in New South Wales, Australia. Kaplan-Meier estimates were used to report HCV treatment uptake by frequency, length, and cause-specific hospitalization. RESULTS: Among 57 467 people, 14 938 (26%) had evidence of recent drug dependence, 50% (n = 7506) of whom were hospitalized while DAA eligible. Incidence of selected cause-specific hospitalization was highest for mental health-related (15.84 per 100 person-years [PY]), drug-related (15.20 per 100 PY), and injection-related infectious disease (9.15 per 100 PY) hospitalizations, and lowest for alcohol use disorder (4.58 per 100 PY) and liver-related (3.13 per 100 PY). In total, 65% (n = 4898) of those who were hospitalized had been admitted ≥2 times, and 46% (n = 3437) were hospitalized ≥7 days. By the end of 2018, DAA therapy was lowest for those hospitalized ≥2 times, for ≥7 days, and those whose first admission was for injection-related infectious disease, mental health disorders, and drug-related complications. CONCLUSIONS: Among people who have evidence of recent drug dependence, frequent hospitalization-particularly mental health, drug, and alcohol admissions-presents an opportunity for engagement in HCV care.

High hepatitis C treatment uptake among people with recent drug dependence in New South Wales, Australia.

BACKGROUND & AIMS: High HCV treatment uptake among people at most risk of transmission is essential to achieve elimination. We aimed to characterise subpopulations of people with HCV based on drug dependence, to estimate direct-acting antiviral (DAA) uptake in an unrestricted treatment era, and to evaluate factors associated with treatment uptake among people with recent drug dependence. METHODS: HCV notifications in New South Wales, Australia (1995-2017) were linked to opioid agonist therapy (OAT), hospitalisations, incarcerations, HIV notifications, deaths, and prescription databases. Drug dependence was defined as hospitalisation due to injectable drugs or receipt of OAT, with indicators in 2016-2018 considered recent. Records were weighted to account for spontaneous clearance. Logistic regression was used to analyse factors associated with treatment uptake among those with recent drug dependence. RESULTS: 57,467 people were estimated to have chronic HCV throughout the DAA era. Treatment uptake was highest among those with recent (47%), compared to those with distant (38%), and no (33%) drug dependence. Among those with recent drug dependence, treatment was more likely among those with HIV (adjusted odds ratio [aOR] 1.71; 95% CI 1.24-2.36), recent incarceration (aOR 1.10; 95% CI 1.01-1.19), and history of alcohol use disorder (aOR 1.22; 95% CI 1.13-1.31). Treatment was less likely among women (aOR 0.78; 95% CI 0.72-0.84), patients of Indigenous ethnicity (aOR 0.75; 95% CI 0.69-0.81), foreign-born individuals (aOR 0.86; 95% CI 0.78-0.96), those with outer-metropolitan notifications (aOR 0.90; 95% CI 0.82-0.98), HBV coinfection (aOR 0.69; 95% CI 0.59-0.80), and >1 recent hospitalisation (aOR: 0.91; 95% CI 0.84-0.98). CONCLUSIONS: These data provide evidence of high DAA uptake among people with recent drug dependence, including those who are incarcerated. Enhancing this encouraging initial uptake among high-risk populations will be essential to achieve HCV elimination. LAY SUMMARY: To facilitate HCV elimination, those at highest risk of infection and transmission are a treatment priority. This study shows the successes of Australia's universal provision of DAA therapy in reducing the barriers to treatment which have historically persisted among people who inject drugs. Despite higher DAA therapy uptake among those with recent drug dependence, gaps remain. Strategies which aim to reduce marginalisation and increase treatment uptake to ensure equitable HCV elimination must be advanced.

Time to Detection of Hepatitis C Virus Infection With the Xpert HCV Viral Load Fingerstick Point-of-Care Assay: Facilitating a More Rapid Time to Diagnosis.

BACKGROUND: Xpert HCV Viral Load Fingerstick assay (Xpert HCV VL FS) is a point-of-care test quantifying HCV RNA in <1 hour, enabling same-visit diagnosis and treatment. METHODS: This study evaluated time to HCV RNA detection using the Xpert HCV VL FS assay. Fingerstick whole-blood samples were collected from participants in an observational cohort in Australia. RESULTS: In May 2018-2019, 1468 participants were enrolled, 1426 had Xpert HCV VL FS testing performed, and 1386 had a valid result. HCV RNA was detected in 23% (325/1386). Among people with undetectable HCV RNA (n = 1061), median time to result was 57 minutes. Among people with detectable HCV RNA (n = 325), median time to HCV RNA detection was 32 minutes and 80% (261/325) had a detectable HCV RNA result in ≤40 minutes. Median time to HCV RNA detection was dependent on HCV RNA level. CONCLUSIONS: A quicker HCV diagnosis could be achieved by monitoring the time when HCV RNA is first detected with the Xpert HCV VL FS test, rather than HCV RNA quantification, although the current platform does not allow for this. These findings could facilitate new strategies to reduce waiting times for an HCV diagnosis and improve linkage to treatment.

Trends in viral hepatitis liver-related morbidity and mortality in New South Wales, Australia.

Background: Monitoring hepatitis B virus (HBV) and hepatitis C virus (HCV) liver-related morbidity and mortality is key to evaluate progress towards elimination targets. Methods: HBV and HCV notifications in NSW, Australia (1995-2022) were linked to hospital and mortality records. Temporal trends in decompensated cirrhosis (DC), hepatocellular carcinoma (HCC), and mortality were evaluated among people notified for HBV and HCV. Segmented Poisson regression models were used to assess the impact of the viral hepatitis elimination era (1 January 2015-31 December 2022) on advanced liver disease and mortality. Findings: During 1995-2022, there were 64,865 people with an HBV notification and 112,277 people with an HCV notification in NSW. Between 2002 and 2022, there were significant reductions in age-adjusted HBV- and HCV-related DC, HCC, and liver-related mortality. Among those with HBV, age-standardised incidence per 1000 person-years (py) in 2002, 2015, and 2022 was 3.08, 1.47, and 1.16 for DC (p < 0.001); 2.97, 1.45, and 0.75 for HCC (p < 0.001); and 2.84, 1.93, and 1.40 for liver-related mortality (p < 0.001). Among those with HCV, age-standardised incidence per 1000 py in 2002, 2015, and 2022, was 5.53, 4.57, and 2.31 for DC (p < 0.001); 2.22, 2.59, and 1.87 for HCC (p < 0.001); and 3.89, 4.73, and 3.16 for liver-related mortality (p < 0.001). In 2022, absolute liver-related mortality per 100,000 population was 0.95 for HBV and 3.56 for HCV. In adjusted analyses, older age, comorbidity, and a history of alcohol use disorder were associated with increased liver-related mortality among those with HBV and HCV. Interpretation: This population-level study demonstrated declining risks of DC, HCC, and mortality, with HBV-related declines commencing well before elimination era while HCV-related declines were mostly during elimination era. Population liver mortality indicates elimination target achieved for combined viral hepatitis and HBV, but not HCV. Funding: The Kirby Institute, UNSW Sydney, and New South Wales Ministry of Health, Australia.

Evaluation of Simplified HCV Diagnostics in HIV/HCV Co-Infected Patients in Myanmar.

To evaluate a decentralised testing model and simplified treatment protocol of hepatitis C virus (HCV) infection to facilitate treatment scale-up in Myanmar, this prospective, observational study recruited HIV-HCV co-infected outpatients receiving sofosbuvir/daclatasvir in Yangon, Myanmar. The study examined the outcomes and factors associated with a sustained virological response (SVR). A decentralised "hub-and-spoke" testing model was evaluated where fingerstick capillary specimens were transported by taxi and processed centrally. The performance of the Xpert HCV VL Fingerstick Assay in detecting HCV RNA was compared to the local standard of care ( plasma HCV RNA collected by venepuncture). Between January 2019 and February 2020, 162 HCV RNA-positive individuals were identified; 154/162 (95%) initiated treatment, and 128/154 (84%) returned for their SVR12 visit. A SVR was achieved in 119/154 (77%) participants in the intent-to-treat population and 119/128 (93%) participants in the modified-intent-to-treat population. Individuals receiving an antiretroviral therapy were more likely to achieve a SVR (with an odds ratio (OR) of 7.16, 95% CI 1.03-49.50), while those with cirrhosis were less likely (OR: 0.26, 95% CI 0.07-0.88). The sensitivity of the Xpert HCV VL Fingerstick Assay was 99.4% (95% CI 96.7-100.0), and the specificity was 99.2% (95% CI 95.9-99.9). A simplified treatment protocol using a hub-and-spoke testing model of fingerstick capillary specimens can achieve an SVR rate in LMIC comparable to well-resourced high-income settings.

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

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

Factors associated with hepatitis C treatment uptake among females of childbearing age in New South Wales, Australia: A population-based study.

INTRODUCTION: Females of childbearing age with hepatitis C virus (HCV) face increased marginalisation with intersecting, sex-specific barriers to direct acting antiviral (DAA) therapy. We assessed the factors associated with uptake of DAA therapy among females of childbearing age, including those with evidence of recent drug dependence. METHODS: HCV notifications in New South Wales, Australia (1995-2017) were linked to opioid agonist therapy (OAT), hospitalisations, incarcerations, perinatal, HIV notifications, deaths and prescription databases. Recent drug dependence was defined as hospitalisation due to injectable drugs or receipt of OAT occurring in the DAA era (2016-2018). Logistic regression was used to analyse factors associated with DAA uptake among females of childbearing age (18-44), including those with recent drug dependence. RESULTS: Among 57,467 people with evidence of chronic HCV in the DAA era (2016-2018), 20,161 (35%) were female, including 33% (n = 6563/20,161) of childbearing age (18-44). Among all females of childbearing age (n = 6563) and those with evidence of recent drug dependence (n = 2278/6563, 35%), DAA uptake was lower among those who had given birth in the DAA era (vs. no birth record, all females of childbearing age; aOR: 0.74, 95% CI 0.61, 0.89; those with recent drug dependence; aOR 0.69, 95% CI 0.51, 0.93) and Aboriginal and Torres Strait Islander peoples (all females of childbearing age; aOR 0.81, 95% CI 0.71, 0.93; those with recent drug dependence aOR 0.75, 95% CI 0.62, 0.90). CONCLUSION: Females of childbearing age should be considered a key population for DAA therapy. Enhancing antenatal and postnatal HCV care may be critical in the pursuit towards elimination.

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

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