A Turning Point for Hepatitis C Care: Point-of-Care HCV RNA Authorization as a Critical First Step Towards Integrated Test-and-Treat Models in the United States

The authorization of Cepheid’s Xpert^® HCV test in June 2024 marks a long-awaited inflection point toward the increasing diversification and adaptability of hepatitis C care models in the United States. This Clinical Laboratory Improvement Amendments (CLIA)–waived, fingerstick-based assay enables point-of-care (POC) hepatitis C virus (HCV) RNA testing with results available in less than one hour. Unlike laboratory-based testing where results may take days to weeks, POC HCV nucleic acid testing can close the gap between diagnosis and treatment initiation by co-locating testing and care in settings that serve people at highest risk. Authorization of the first point-of-care HCV RNA test in the United States represents a necessary first step toward integrated test-and-treat models. Realizing its potential, however, will require thoughtful redesign of certain care pathways and sustained implementation support.

Hepatitis C elimination offers a triple benefit: it saves lives, reduces onward transmission, and lowers healthcare costs by preventing HCV-related complications [1]. The National Academies of Science, Engineering, and Medicine have estimated that 90% of people with hepatitis C must be diagnosed and 80% of people diagnosed must be treated to reach elimination [2]. However, about one-third of people with hepatitis C remain unaware of their infection and fewer than one-third who are diagnosed initiate curative treatment within one year of diagnosis [3, 4]. Traditional care models, which rely on phlebotomy, laboratory infrastructure, multiple visits, and often specialist referral, work for some but perpetuate disparities for people with hepatitis C who use drugs, are incarcerated, or experience homelessness or severe mental illness. The long-recognized need for a POC device capable of diagnosing current infection during a single-encounter without the need for phlebotomy coincided with the Food and Drug Administration’s (FDA) down-classification of HCV diagnostics and a federal partnership between the Centers for Disease Control and Prevention (CDC), the National Institutes of Health (NIH), and FDA through the NIH’s Independent Test Assessment Program (ITAP).

ITAP was created during the COVID-19 pandemic to accelerate the evaluation of novel diagnostics. In late 2022, ITAP pivoted to hepatitis C and with the support of CDC and NIH launched a solicitation for POC HCV RNA tests. ITAP first met with Cepheid in May 2023, and within 13 months of that meeting, completed the data collection required for FDA authorization, including a prospective 15-site clinical evaluation conducted in just four months and reported by Havens et al. [5]. The study demonstrated high positive and negative percent agreement with laboratory-based HCV RNA testing across diverse real-world CLIA-waived settings relying on operators with no training on the system and with only limited instructions. Together with a low limit of detection of <100 IU/ml for most HCV genotypes, these data supported FDA de novo authorization [6].

Although Xpert^® HCV represents an important breakthrough, several limitations have implications for its implementation and scalability. First, there is a learning curve associated with collecting 250 μL of capillary fingerstick blood using a high-flow lancet and microtainer and then accurately transferring the specimen into the cartridge. In the clinical study, 10% (133/1,279) of participants were excluded because of insufficient fingerstick collection, and 6% (61/1,015) of tests initially yielded indeterminant results—although 80% (49/61) of these produced valid results upon retesting [5]. Second, in contrast to an instrument-free ‘true’ POC diagnostic, Xpert^® HCV functions as a ‘near’ POC diagnostic because it requires an Xpert^® Xpress instrument that must be purchased or leased and maintained according to quality assurance standards. This introduces additional training requirements and costs, which are not fully offset by current reimbursement for HCV RNA testing. Third, despite its early termination feature allowing for detectable RNA results within 41 minutes, the turnaround time may still present workflow challenges during high-volume testing campaigns or in brief-encounter settings where patients may leave before results are available. Finally, the current FDA authorization does not extend to Xpert^® HCV use in pediatric populations (<21 years), pregnant women, assessment of sustained virologic response, or use with venous whole blood samples, although future expansions may address these gaps. These limitations are real but surmountable. Countries such as Australia have successfully piloted and scaled highly successful national HCV point-of-care testing programs despite similar constraints [7].

The key question now is where POC HCV RNA testing can have the greatest impact. Clinical settings such as primary care practices and office-based opioid treatment programs that already have phlebotomy services, laboratory access, and longitudinal patient follow-up may find it more practical to continue laboratory-based testing workflows. In contrast, non-clinical settings such as syringe services programs and opioid treatment programs or brief-encounter environments like jails and mobile health units often serve populations with high hepatitis C prevalence who are less likely to return for follow-up care. In these settings, POC HCV RNA testing can enable rapid, on-site diagnosis that is paired with rapid or even same-encounter treatment initiation.

Another key consideration is whether to implement a single-step strategy (offering only POC HCV RNA testing to all persons) or a two-step strategy (POC HCV antibody testing followed, when reactive, by POC HCV RNA testing). A single-step approach has the advantage of identifying early infections before antibodies are detectable. However, economic analyses from Australia suggest that a two-step strategy may be more cost-efficient except in settings with HCV seroprevalence above 70% [8]. Operationally, a two-step approach may also be easier to manage due to the lower cost, shorter turnaround time, and simpler sample collection with POC HCV antibody tests. Regardless of the strategy, POC HCV RNA testing must be coupled with systems that streamline prescribing and medication access. Without rapid treatment pathways, investments in POC diagnostics risk building bridges to nowhere.

International evidence underscores this point. In Australia, the PROMPt study integrated POC HCV RNA testing across prison, inpatient mental health, and alcohol and drug treatment settings, more than doubling HCV testing and significantly increasing treatment initiation [9]. Similarly, the PIVOT study in an Australian reception prison reduced time to treatment from 99 days to 6 days and increased uptake from 22% to 93% under a same-encounter test-and-treat model [10]. In the United States, studies including ACCESS (NCT06730555) and CREST are underway to inform how to integrate POC test-and-treat models in the U.S. context. The Substance Abuse and Mental Health Services Agency Hepatitis C Elimination pilot (TI-25-005) has also awarded $98 million over two years to integrate same-day testing and treatment initiation in substance use disorder treatment settings. Together, these efforts aim to accelerate adoption of integrated care models.

FDA authorization of a POC HCV RNA test is a critical first step toward integrating hepatitis C test-and-treat models in the United States but is not sufficient on its own for achieving elimination. Complementary efforts including the development of the new AASLD/IDSA POC test-and-treat algorithm, ongoing work with ITAP to bring a POC hepatitis B surface antigen test to market, a new 2027 Medicaid Adult Core Set measure tracking HCV testing and rapid treatment initiation, and the $10 billion proposed investment in elimination from the Cure Hepatitis C Act will determine whether this diagnostic milestone translates into population-level impact. Thanks to the work of Havens et al., the essential building blocks of elimination are now in place. The challenge ahead is to move from authorization to care transformation.