Point-of-Care Testing for Hepatitis C Infection: A Critical Building Block for the Foundation to Achieve Elimination

(See the Major Article by McCartney et al. on pages 965–73.)

A barrier to improving hepatitis C virus (HCV) testing and treatment and achieving elimination is that the current diagnostic pathway requires multiple visits (HCV antibody to confirm exposure, HCV RNA to confirm active infection, and one or more assessments to start treatment), leading to loss to follow-up [1]. This is amplified in populations with high HCV burden, such as people who inject drugs and those in prison.

A fingerstick point-of-care test to detect current HCV infection in 1 hour [2, 3] is a “game changer,” as it enables diagnosis and treatment in a single visit and increases testing acceptability, overcoming the barrier of multiple visits leading to loss to follow-up [1]. The Xpert HCV Viral Load Fingerstick assay has excellent technical accuracy [2–4] and clinical utility [4–6]. Point-of-care HCV RNA testing programs have been successfully implemented in a range of settings, including prisons [7], mobile clinics [8], community clinics [9–11], needle/syringe programs [12–14], and overdose prevention sites [15, 16]. Clinical studies of point-of-care HCV RNA testing using the Xpert HCV Viral Load Fingerstick assay have demonstrated shortened time to diagnosis, and increased testing, linkage to care, and treatment compared with the standard of care [4–6].

In this issue of Clinical Infectious Diseases, McCartney and colleagues [17] evaluated the effect of combined point-of-care HCV antibody and RNA testing on acceptability and rates of HCV antibody testing, RNA testing, and treatment uptake compared with the standard of care in prison, drug treatment, and mental health settings between December 2019 and December 2021 in Australia. Among people receiving point-of-care HCV antibody testing (n = 1549), 98% indicated a preference for same day point-of-care testing, and 84% said they felt it was important to receive test results on the same day. Among those who were HCV antibody positive (17% [264 of 1549]), 100% received reflexive RNA testing.

Combined point-of-care HCV antibody/reflexive RNA testing was associated with a 3-fold increase in the rate of HCV antibody testing/year (relative risk [RR], 2.57 [95% confidence interval (95% CI)], 2.32–2.85) and nearly a 2-fold increase in the rate of HCV RNA testing per year (1.62 [1.31–2.01]), compared with a historical control (December 2019 to December 2020). These increases were driven primarily by increased rates of HCV antibody testing (RR, 8.86 [95% CI, 6.67–11.99]) and RNA testing (5.68 [3.33–10.34]) in the drug treatment clinic setting. Treatment uptake was 86% (47 of 55) in the combined point-of-care HCV antibody/reflexive RNA group compared to 61% (27 of 44; P = .01) in the historical control group. Study limitations included the design (participants were not randomized) and data collection (some demographic data from the historical controls were not available, precluding an ability to adjust for characteristics between the 2 periods).

This important study by McCartney and colleagues [17] demonstrates the critical role of combined point-of-care HCV antibody and reflexive RNA testing to increase testing and treatment. Results are consistent with a systematic review demonstrating that point-of-care HCV RNA testing is associated with increased treatment uptake (pooled RR, 1.32 [95% CI, 1.06–1.64]) [6]. The current study adds to the literature by evaluating a combined point-of-care HCV antibody and RNA testing strategy (most studies have investigated immediate point-of-care RNA testing), with the inclusion of a historical comparator group (most studies have been single arm) and the inclusion of multiple settings. These data support guidelines by the World Health Organization recommending clinic-based reflexive HCV RNA testing following a positive HCV antibody test result (point-of-care or laboratory-based determination) and the use of point-of-care RNA testing in HCV clinical management [18].

This study highlights the importance of combining HCV antibody testing with reflexive RNA testing, compared with proceeding to immediate point-of-care RNA testing, depending on the setting. While immediate point-of-care RNA testing might be considered in high-prevalence settings (eg, drug treatment clinic or overdose prevention site), in settings with low to moderate HCV antibody prevalence (eg, prisons, needle-syringe programs, or homelessness services), it might make more sense to implement point-of-care HCV antibody and reflexive RNA testing, for several reasons [1]. Point-of-care HCV antibody tests are less expensive and have a shorter time to result than point-of-care RNA tests (1–20 vs 60 minutes, respectively), improving acceptability among patients and providers and reducing the likelihood that someone will leave before receiving their test result. Point-of-care HCV antibody tests are less complex to administer and require less intensive operator training and less time to conduct the test. Point-of-care antibody tests can reduce the number of RNA tests performed, thereby lowering the number of error/invalid RNA test results (often resulting from inadequate sample collection). Point-of-care antibody testing can increase the throughput of RNA tests by improving the use of the GeneXpert system and reducing the burden/workload on clinic staff. Finally, combined point-of-care HCV antibody/reflexive RNA testing is more cost-effective than immediate point-of-care RNA testing across a range of settings up to an HCV antibody prevalence of 74% (albeit based on Australian parameters) [19].

A practical testing strategy would be to offer immediate point-of-care HCV RNA testing in people with self-reported knowledge of exposure and offer combined point-of-care HCV antibody/reflexive RNA testing to all others. Preliminary data from McCartney and colleagues [17] (and the rationale above) informed our approach to implement this algorithm as part of the National Australian Hepatitis C Point-of-Care Testing Program [20]. This program has partnered with more than 150 researchers, health service providers, community organizations, and policy makers to scale up point-of-care HCV antibody and RNA testing at 90 sites in Australia. Program sites include drug treatment clinics, needle and syringe programs, prisons, mobile outreach models, homelessness services, Aboriginal community-controlled health organizations, and mental health services. The program facilitates point-of-care testing for anyone at risk of HCV or attending a service providing care for people at risk of HCV.

Between January 2022 and August 2023, 74 sites (53 community and 21 prison sites) have been established nationally, with 13 689 HCV point-of-care tests performed (2149 antibody and 11 540 RNA tests) [21]. The strategy of combined HCV antibody/RNA testing has been implemented more recently according to the algorithm described above. Among 11 853 people receiving testing (39% at community and 61% at prison sites), 1668 (14%) have current HCV infection (10% at community and 16% at prison sites), and 79% have initiated treatment (52% at community and 89% at prison sites). Overall, 9% of HCV treatment in Australia is being facilitated through this program [21], which is among the first internationally to evaluate point-of-care HCV testing scale-up and could be used as a model for other countries (eg, the United States [22]).

Several critical components are required to scale-up point-of-care HCV testing. Point-of-care HCV antibody test availability is essential, including tests with faster times to result (eg, the Bioline HCV test [5 minutes to positive result] or the INSTI HCV test [1 minute to result]). The down-classification of HCV antibody tests by the Food and Drug Administration make it easier for manufacturers to conduct studies required for regulatory approval, and other regulatory agencies globally should consider similar changes. Given the need to exclude human immunodeficiency virus (HIV) and hepatitis B virus (HBV) infections as causes of comorbid conditions before the start of HCV treatment, point-of-care tests for HIV and HBV will facilitate single-visit HCV treatment models (although this shouldn’t be a deal breaker, as these tests can be ordered at the time of treatment initiation and results reviewed within 1–2 weeks). A point-of-care test for alanine aminotransferase/aspartate aminotransferase/platelets would also be helpful (although the lack of such testing shouldn’t preclude treatment, as decompensated disease can be clinically determined without the need for these tests at treatment initiation).

Changes to clinical guidelines and reimbursement mechanisms are needed to allow a single HCV RNA detectable test as evidence of current infection for single-visit treatment (irrespective of acute or chronic disease), consistent with guideline changes in Australia [23]. Prison-based HCV point-of-care testing and treatment programs (including high-intensity testing campaigns) have been (and will be) critical. Greater investment is needed for development and sustainability point-of-care testing programs. This should include funding for development/maintenance of quality assurance programs, operator education/training, and program implementation (eg, clinical and peer workforces). Investment in information technology/connectivity solutions is critical to ensure delivery of test results (and associated information) into medical records, government public health databases for infection notification, and surveillance systems to monitor program effectiveness. Research is needed to understand interventions to enhance point-of-care HCV testing and treatment, including implementation science and social science research to better understand what works with point-of-care testing and why. Health economics and modeling is critical to determine the cost-effectiveness of point-of-care testing to support investment cases to health policy makers.

In April 2023, a group of experts at the 2023 INHSU Hepatitis C Point-of-Care Testing Forum before the 2023 Global Hepatitis Summit (Paris, France) discussed barriers and solutions for increasing access to point-of-care HCV testing. Solutions were proposed to address barriers related to governance, workforce and quality assurance, health information systems, financing, and service delivery within a health systems framework (Figure 1). Recommendations from this report could overcome barriers and expand global access to point-of-care HCV testing [24].

Figure 1.

Recommended solutions to address governance, workforce and quality assurance, health information systems, financing, and service delivery barriers for expanding global access to point-of-care hepatitis C virus (HCV) testing (adapted from the International Network on Health and Hepatitis in Substance Users [24] with permission). Abbreviation: IT, information technology.

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Although there has been some progress in expanding point-of-care testing access, work is needed to achieve greater scale-up. Facilitating more rapid access and implementation of point-of-care testing is a critical component of the United States elimination plan [22, 25]. We must move with more urgency to implement available innovations, such as point-of-care testing, as critical building blocks to form a foundation for HCV elimination in the United States and globally.

Notes

Acknowledgments. The author acknowledges the authors of the report from the 2023 INHSU Hepatitis C Point-of-Care Testing Forum, including Emma Day, Susan Matthews, Corey Markus, Elisa Martro, Saeed Hamid, Jonas Demant Hansen, John Ward, Oriel Fernandez, Jordan Feld, and Jean-Michel Pawlotsky. The meeting was convened by the International Network on Health and Hepatitis in Substance Users, in collaboration with the Coalition for Global Hepatitis Elimination, Foundation for Innovative New Diagnostics, The Kirby Institute, UNSW Sydney, and the Clinton Health Access Initiative. This report is based on presentations and roundtable discussions during that meeting. The author also acknowledges the speakers, facilitators, and attendees and the Global Hepatitis Summit organizers for their participation and support.

Disclaimer. The views expressed in this publication do not necessarily represent the position of the Australian government.

Financial support. The Kirby Institute is funded by the Department of Health and Ageing, Australian Government, and J. G. is supported by the National Health and Medical Research Council (investigator grant 1176131).

References

Author notes