Point-of-Care Testing for Hepatitis C in the Priority Settings of Mental Health, Prisons, and Drug and Alcohol Facilities—the PROMPt Study

Abstract

Background

A barrier to hepatitis C virus (HCV) cure is conventional testing. The aim of this study was to evaluate the effect of HCV antibody and RNA point-of-care testing (POCT) on testing rates, linkage to care, treatment, and acceptability of testing in 3 priority settings in Australia.

Methods

Participants were enrolled in an interventional cohort study at a reception prison, inpatient mental health service, and inpatient alcohol and other drug unit, between October 2020 and December 2021. HCV POCT was performed using SD Bioline HCV antibody fingerstick test and a reflexive Xpert HCV Viral Load Fingerstick test using capillary blood samples. A retrospective audit of HCV testing and treatment data was performed at each site for the preceding 12-month period to generate a historical control.

Results

A total of 1549 participants received a HCV antibody test with 17% (264 of 1549) receiving a positive result, of whom 21% (55 of 264) tested HCV RNA positive. Across all settings the rate of testing per year significantly increased between the historical controls and the study intervention period by 2.57 fold (rate ratio, 2.57 [95% confidence interval, 2.32–2.85]) for HCV antibody testing and 1.62 (rate ratio, 1.62 [95% confidence interval, 1.31–2.01]) for RNA testing. Treatment uptake was higher during the POCT intervention (86% [47 of 55]; P = .01) compared to the historical controls (61% [27 of 44]).

Conclusions

This study demonstrated across 3 settings that the use of HCV antibody and RNA POCT increased testing rates, treatment uptake, and linkage to care. The testing model was highly acceptable for most participants.

Clinical Trials Registration

ACTRN-12621001578897

(See the Editorial Commentary by Grebely on pages 974–7.)

An estimated 58 million people are infected with hepatitis C virus (HCV) worldwide, with 1.5 million new infections occurring each year [1]. The majority of infections lead to chronicity (65%–75%) and an increased morbidity and mortality risk from liver cirrhosis, liver failure, and hepatocellular carcinoma [2, 3]. Direct-acting antiviral (DAA) treatment now offers a curative therapy and can prevent these long-term complications [4].

The World Health Organization developed targets to achieve the elimination of HCV as a public health threat by 2030. Although Australia was one of the first countries to introduce unrestricted access to DAAs in 2016, it may miss these targets due to declining rates of testing and treatment [5–7]. For these targets to be actualized, new strategies are urgently required to scale up testing and linkage to care, particularly for marginalized individuals at high risk of HCV infection [7–11].

A key barrier to achieving linkage to care is the multistage process of conventional HCV testing [12]. This model requires patients to undergo multiple visits to pathology services and healthcare providers to obtain a HCV antibody test and a subsequent HCV RNA test, then return to the clinic for a result, and finally be linked with a DAA prescriber for treatment [13]. Furthermore, conventional models use venipuncture for HCV testing, which has been shown to be a deterrent for individuals accessing testing, especially for people who inject drugs (PWID), who often have difficult venous access [14]. The Xpert HCV Viral Load Fingerstick point-of-care testing (POCT) has demonstrated high technical accuracy in a number of studies [15, 16]. Systematic reviews have shown that HCV antibody and RNA POCT assays reduce the time from antibody test to treatment initiation and uptake [17], increase RNA testing and DAA treatment initiation [18], and significantly improve the uptake of HCV antibody testing, linkage to care, and uptake of DAA treatment [18]. However, few studies using combined HCV antibody and RNA POCT have included a standard-of-care (SOC) comparator arm, nor were they conducted concurrently across multiple settings.

The aim of this study, conducted as part of the Eliminate Hepatitis C (EC) Australia Partnership, was to evaluate the effect of HCV antibody and RNA POCT on testing rates and acceptability, linkage to care, and treatment in 3 priority settings—reception prison, an alcohol and other drug (AOD) inpatient unit, and an inpatient mental health service (MHS) in South Australia, Australia.

METHODS

Study Design

PROMPt was a prospective interventional cohort study with a historical control that evaluated the introduction of HCV antibody and RNA POCT in the priority settings of a reception prison, an inpatient AOD unit, and an inpatient MHS. This study was registered with Clinical Trials AZNCTR (ACTRN-12621001578897). Ethical approval was granted by the Central Adelaide Local Health Network Human Research Ethics Committee (HREC13046).

Setting

PROMPt was conducted at 3 priority settings within metropolitan Adelaide, South Australia: a maximum-security prison facility used to hold prisoners on remand pending trial (reception prison), an inpatient AOD unit, and an inpatient MHS. Due to delays with site initiation, the intervention arm commenced at the AOD unit 2 months later than the other sites. The time periods for the interventional cohort were October 2020 to October 2021 for both the impatient MHS and the reception prison and December 2020 to December 2021 for the AOD unit.

Procedures

Intervention POCT Cohort

The tests used in this study were the SD Bioline (Abbott) HCV antibody point-of-care fingerstick test, using capillary blood samples, and the Xpert HCV Viral Load Fingerstick assay on the GeneXpert system (Cepheid), which provides a quantitative HCV RNA viral load result from a capillary blood sample.

Real-world implementation studies have estimated that the sensitivity of detection for the SD Bioline antibody HCV test ranges between 94.0% and 99.4%, and the specificity ranges between 98.0% and 100.0% [19, 20]. Based on meta-analysis for the Xpert HCV Viral Load Fingerstick, the estimated sensitivity and specificity for HCV RNA detection were 99% (95% confidence interval [CI], 97%–99%) and 99% (94%–100%), respectively [15, 16, 21, 22]. For this study, HCV RNA detected at any viral load was deemed a positive result.

The study team performing POCT at the settings consisted of a nurse trained in viral hepatitis management and experienced HCV peer educators. Both the peer educators and nurse administered POCT, reported results to participants, and provided pretest and posttest counseling and harm reduction education.

Participants provided 10 µL of capillary whole blood for the HCV antibody test. This test was read visually, with positive results available at 5 minutes and negative results available after 20 minutes. Participants with a positive HCV antibody result were offered a HCV RNA test and provided 100 µL of capillary whole blood. HCV RNA test results were available after 60 minutes. Results were communicated in person by the study team on the same day testing was conducted. Participants who returned detectable HCV RNA levels were linked to treatment. Linkage to care consisted of the clinical service staff being notified of the positive HCV RNA results and participant details being sent to the local viral hepatitis nurse service for management and treatment. For this study, linkage to care was defined as phone contact with a viral hepatitis nurse, an appointment attended, or a prescription for medication given to the participant.

Historical Control

To assess whether there were increases in HCV testing and treatment rates during the intervention period, we conducted a retrospective clinical audit of HCV antibody and RNA testing and treatment data for all admissions in the preceding year for each setting. Data were collected from medical records and via the centralized pathology service in Adelaide. All sites used conventional venipuncture collection and laboratory-based pathology services for HCV antibody and RNA testing during this time. Duplicate tests for the same individual were removed from final analysis. Rates of HCV antibody and RNA testing were calculated for both the intervention year and the year preceding in each setting (no. of antibody or RNA tests/total admissions). Rate ratios (RRs) were also calculated for both antibody and RNA testing.

Follow-up

For the interventional cohort, we used a 6-month follow-up period to assess linkage to care and commencement of treatment among participants who received a positive HCV RNA POCT. For the historical control, we used a 6-month follow-up period to assess linkage to care and commencement of treatment and a 12-month period to assess sustained virologic response (SVR) testing among participants who received a positive RNA test result.

Participants

Consent was opt-in, and all participants were aged ≥18 years and were not currently engaged in HCV treatment. Study staff verbally consented participants and conducted mobile POCT at each setting. Posters and pamphlets were displayed at all 3 settings, and staff were encouraged to discuss the study with clients to raise awareness.

Data Sources

Data Collection

Participants completed a survey while waiting for the HCV antibody test results. The survey collected demographic data, previous HCV testing history, and participant attitudes toward HCV POCT. Data were collected using REDCap (Research Electronic Data Capture) software, version 10.6.28 (Vanderbilt University; https://www.project-redcap.org/).

Outcomes

The primary outcomes of the study were the number and proportion of participants who underwent HCV antibody and RNA POCT, were linked to care, and began treatment. We used RRs to assess changes in the yearly rate of antibody and RNA testing between the intervention period and the historical comparison period, both overall and within each setting. Secondary outcomes were the acceptability of POCT among participants and the time from diagnosis to commencement of treatment in the interventional cohort.

Statistical Methods/Analysis

Rate of HCV antibody and RNA testing were calculated for the intervention year and the historical control, both overall and relative to admissions (no. of antibody or RNA tests/total admissions in year). To assess for changes in HCV testing rates between the intervention and historical control periods, RRs were calculated for both antibody and RNA testing. Fisher exact test was used to assess changes in treatment uptake between the intervention period and the historical control period. Differences were considered statistically significant at P < .05, and statistical analysis was performed using Stata software, version 16.1 (StataCorp).

RESULTS

Participant Characteristics for POCT Intervention Cohort

In total, 1549 participants were enrolled into the study and received a HCV antibody test. Participant characteristics for each priority setting are summarized in Table 1. Figure 1 displays the study design and the total numbers of participants who underwent testing and results. The median age for the total population was 37 years (interquartile range [IQR], 30–46 years); 1290 participants (83%) were male, and 379 (25%) self-identified as Aboriginal/Torres Strait Islander. More than half (54%) reported previously having a test for HCV (antibody or RNA). Of the 55 participants who tested RNA positive, 29 (53%) reported that they were experiencing homelessness within 90 days of testing (Table 2).

Acceptability of POCT Methods

The results of a self-reported survey for HCV POCT acceptability are summarized in Table 3. The majority of participants (98%) indicated a preference for same-day HCV POCT compared with standard venipuncture and laboratory-based tests. Four in 5 (84%) responded that it was important to receive their HCV test results on the day of testing. The acceptability of POCT methods was comparable across all 3 settings.

POCT Intervention Results

Results of HCV antibody and RNA POCT are summarized in Table 4. One in 5 participants (17%) tested HCV antibody positive, of whom 100% received reflexive RNA testing. Proportions of chronic HCV infection were low across the study, with a positive HCV RNA result in 4% of participants (55 of 1549). Among participants who with a positive HCV antibody test result, HCV RNA test positivity was present in 21% (55 of 264).

Comparison of HCV Testing Rates Between POCT Intervention Period and Historical Controls

Across all 3 settings, there was an approximate 3-fold (RR, 2.57 [95% CI, 2.32–2.85]) increase in the rate of HCV antibody testing per year in the intervention period compared with the historical control period Table 5. When stratified by setting, HCV antibody testing approximately doubled in the MHS (RR, 1.88 [95% CI, 1.48–2.41]) and reception prison (2.01 [1.77–2.30]) and increased 9-fold in the inpatient AOD unit (8.86 [6.67–11.99]). There was an approximately 2-fold increase in RNA testing rate across all 3 settings (RR, 1.62 [95% CI, 1.31–2.01]) in the intervention period compared with the historical control period (Table 5). However, when stratified by setting, this increase was driven largely by the AOD setting (RR, 5.68 [95% CI, 3.33–10.34]), with no evidence of an increase observed in the reception prison (1.2 [96–1.65]) or the MHS (0.72 [.36–1.38]). Antibody positivity was similar between the intervention and historical control period across all 3 settings. HCV RNA positivity decreased from 33% in the historical control period to 21% during the POCT intervention period.

Linkage to Care/Treatment

Results in Tables 6 and 7 demonstrate that, for the intervention arm, of 55 participants who received a positive RNA result, 91% (50 of 55) were linked to care and 86% (47 of 55) began treatment. The median (IQR) interval from referral to treatment was 14 (5–30) days.

Of the 39 participants who tested positive for HCV RNA at the reception prison, 95% (37 of 39) were linked to care and began treatment. The median (IQR) interval from referral to treatment was 14 (5–43) days. At the inpatient AOD unit, 10 participants produced positive HCV RNA results, of whom 70% (7 of 10) were linked to care and 60% (6 of 10) began treatment. The median (IQR) interval from referral to treatment was 20 (5–27) days. At the inpatient MHS, 100% of participants (6 of 6) who received a HCV RNA–positive result were linked to care, and 67% (4 of 6) began treatment. The median (IQR) interval from referral to treatment was 2 (1.5–2.0) days.

Table 7 depicts treatment data for the HCV RNA–positive participants in the historical control group, In the total population, 61% began treatment following a positive HCV RNA result. Results differed between the study sites, with 66% beginning treatment at the reception prison, 50% in the AOD, and 0% in the inpatient MHS. Comparing treatment data, the POCT intervention significantly increased treatment uptake, from 61% to 86% (P < .001).

DISCUSSION

Our study demonstrates that the use of HCV antibody and RNA POCT in 3 priority settings led to increased HCV antibody and RNA testing rates and treatment uptake, and that this is a highly acceptable model of testing for people at high risk of HCV. Our model provided streamlined linkage to care to participants with a diagnosis of chronic hepatitis C and overcame significant barriers known to prevent people at risk of HCV from accessing HCV testing and treatment. One major strengths of this study was the use of combined HCV antibody and reflexive HCV RNA POCT, which did not require a venous blood sampling. The benefit of combined testing is that it is a more cost-effective model than RNA POCT alone, as demonstrated by a 2023 study in drug treatment clinics, needle and syringe programs, and prisons [23]. Antibody POCT also has a lower complexity of training for operators and a reduced wait time for results (5–20 minutes for antibody test vs 60 minutes for RNA test). The utility of the rapid HCV antibody fingerstick test allowed more participants to be screened per session, as opposed to using only the more time-consuming and expensive Xpert HCV Viral Load Fingerstick test as the sole testing tool.

While RNA testing rates and RRs increased overall in the intervention arm, most notably in the AOD setting, we observed only a modest increase in the reception prison and a decrease in RNA testing rates in the inpatient MHS. One possibility is that risk-based testing was doing an acceptable job in these settings; however, this approach may overlook people with HCV who do not have obvious risk factors.

This model was extremely effective at linking RNA-positive participants to care, with nearly all participants at the reception prison (95%) and inpatient MHS (100%) successfully referred on for treatment. This supports previous research highlighting streamlined POCT as a strategy for engaging and retaining people with hepatitis C in the HCV care cascade [14, 17]. Furthermore, the same-day HCV testing approach in our study has been successfully implemented outside well-resourced high-income settings, including Myanmar [24], Egypt [25], and Malaysia [26].

The model of care used in this study combined the skills and experience of HCV peer educators and a nurse highly skilled in viral hepatitis management to engage and educate participants. Similar to previous studies, the integration of peer educators contributed significantly to the engagement of participants in the study at each setting [14, 27]. The combined HCV antibody test with reflexive RNA testing provided important opportunities for harm reduction education relating to risk factors of HCV transmission. This proved to be a key facilitator in ensuring that participants who tested HCV antibody positive underwent reflexive RNA testing, with 100% of participants who tested HCV antibody positive receiving a subsequent RNA test. Consistent with other studies, most participants indicated that they preferred the fingerstick test that provided same-day results over standard venipuncture and laboratory-based testing [28].

In most high-income countries, including Australia, the HCV epidemic has been primarily concentrated among PWID. Consequently, it is critical that HCV models of care are appropriately tailored for PWID, including adopting a stigma-free and person-centered approach. Previous studies offering HCV POCT among PWID have exhibited varying levels of treatment uptake and linkage, ranging between 49% and 97% [26, 29–31]. In our study, we achieved high linkage to care across all 3 priority settings. While the reasons for this are multifaceted, key factors in our model that may have contributed to this result are the combined HCV antibody and RNA POCT, the removal of venous blood samples, and the fact that all participants were housed within each of the services for our study. Homelessness was cited as a major prohibitive factor for linkage and treatment initiation, which was similarly observed in our study, with almost half of all participants testing RNA positive and all participants not linked to care reporting a recent history of homelessness. This marginalized population remains a priority group in urgent need of refined models of care to cure HCV [32]. Within the reception prison, our model enabled high levels of participant recruitment. Other studies support this finding, with POCT studies conducted in English [33] and Australian [34] prisons also demonstrating high engagement with HCV testing and treatment.

RNA positivity was considerably lower in the inpatient AOD unit than in the other settings. Possible reasons for this include the fact that most clients at this service were being treated for alcohol dependency, indicating that other settings may be better suited to a targeted HCV testing approach. Antibody positivity, however, was the highest in the AOD. It is also possible that HCV treatment is better administered in this setting where clinicians being aware of screening and treatment procedures. Interestingly, RNA positivity was the highest in the inpatient MHS, the only setting to show an increase in RNA positivity between the periods before and after POCT intervention. This population also had the lowest number of participants previously tested for HCV, consistent with the history of MHSs being an underserviced area of HCV testing and treatment [35]. This finding highlights the possibility that clinicians may not be clear on HCV testing and treatment guidelines. Also of note, all RNA-positive participants in this setting were successfully linked to care, suggesting that further investigations in MHS settings could yield significant gains in reaching a high-risk population.

The findings in this study demonstrate a scalable model of HCV testing that can increase testing rates and treatment uptake in high-risk settings and provides insights for shaping future policies and healthcare pathways aimed at HCV eradication. This is of particular importance for the HCV 5-year elimination plan in the United States, that sites use HCV POCT technologies and focus on at-risk populations as part of the road map to reach HCV eradication within this time frame [36]. Furthermore, the updated World Health Organization HCV elimination guidelines recommend simplifying HCV testing and treatment pathways, with a focus on high-risk settings, such as prisons, and the routine use of HCV RNA POCT [37]. Our findings support these recommendations and provide important insights for implementing POCT in high-risk settings and continuing progress toward global HCV elimination targets.

We acknowledge the following limitations of this study. Uptake of HCV POCT was not measured because the consent process was opt-in. HCV testing performed per SOC protocols was not recorded during the POCT intervention period; however, the effect on the overall testing rates during the intervention period was believed to be minimal to none. Staff reported that minimal to no SOC HCV testing occurred at all 3 settings during the intervention period as the study team became integrated within the services and offered regular HCV POCT sessions. While SVR data collection for the treated participants would have been beneficial, the effectiveness of DAA therapy and emerging data indicate that it is highly probable that all participants beginning treatment in this study will achieve SVR, even those who were lost to follow-up or failed to complete their full course of treatment [38–43]. Another limitation of this study was the absence of demographic and clinical characteristics for the historical control group. Thus, we are not able to conclusively discern whether observed differences between pre- and postintervention periods are due to differences in participant characteristics. However, we believe that the impact of such differences was minimal, as it is likely the participants tested in the POCT intervention cohort may be a higher-risk population that has become even more difficult to test and treat over time.

As another possible limitation, this study was conducted during the coronavirus disease 2019 (COVID-19) pandemic, when lockdowns during outbreaks affected recruitment and access to settings at various times during the year. Particularly at the beginning of the pandemic, COVID-19 may have reduced the number of tests performed during the preintervention testing period because of interruptions to services within each setting. Despite these limitations, our study provides valuable data that can aid in increasing HCV testing and linkage to care in priority settings.

In conclusion, this study has demonstrated that it is feasible to increase HCV testing rates and treatment uptake in priority settings, using a combined model of HCV antibody and RNA POCT to provide a diagnosis in a single visit, and that this model was highly acceptable to participants. Homelessness was a significant factor prohibiting linkage to care and HCV treatment and as such remains an area of need for further models of care to be developed within the community.

Notes

Acknowledgments. The authors thank study participants and site staff for their invaluable contribution to this study. They also gratefully acknowledge peer educators Lisa Carter and Deborah Warneke-Arnold for their vital role in this study and the contributions of the Eliminate Hepatitis C (EC) Australia Executive Committee and Advisory Committee members and the EC Australia Project Team to this work.

Author Contributions. Conceptualization: T. R., D. S., and C. F. Methodology: E. M. M., L. R., J. D., J. R., A. W., V. C., E. Y. T., T. R., D. S., and C. F. Visualization: E. M. M., L. R., D. S., and C. F. Funding acquisition: T. R., D. S., and C. F. Project administration: E. M. M., L. R., and C. F. Resources: E. M. M., L. R., and C. F. Supervision: J. D., J. R., A. W., V. C., E. Y. T., T. R., D. S., and C. F. Data—curation: E. M. M., L. R., J. D., and J. Z. Formal analysis: E. M. M., J. D., and J. Z. Writing—original draft: E. M. M. Writing—review and editing: E. M. M., L. R., J. D., J. R., A. W., V. C., E. Y. T., T. R., D. S., and C. F.

Disclaimer. The funding body was not involved in the project design, data collection, interpretation, and analysis or manuscript preparation.

Financial support. This work was supported by the Eliminate Hepatitis C (EC) Australia Partnership, funded through the Paul Ramsay Foundation (2019–2022) with support from the Burnet Institute.

References

Author notes