Evaluation of the Xpert HCV Viral Load point-of-care assay from venepuncture-collected and finger-stick capillary whole-blood samples: a cohort study

doi:10.1016/S2468-1253(17)30075-4

The Lancet Gastroenterology & Hepatology

Volume 2, Issue 7, July 2017, Pages 514-520

https://doi.org/10.1016/S2468-1253(17)30075-4 Get rights and content

Summary

Background

Point-of-care hepatitis C virus (HCV) RNA testing offers an advantage over antibody testing (which only indicates previous exposure), enabling diagnosis of active infection in a single visit. In this study, we evaluated the performance of the Xpert HCV Viral Load assay with venepuncture and finger-stick capillary whole-blood samples.

Methods

Plasma and finger-stick capillary whole-blood samples were collected from participants in an observational cohort enrolled at five sites in Australia (three drug and alcohol clinics, one homelessness service, and one needle and syringe programme). We compared the sensitivity and specificity of the Xpert HCV Viral Load test for HCV RNA detection by venepuncture and finger-stick collection with the Abbott RealTime HCV Viral Load assay (gold standard).

Findings

Of 210 participants enrolled between Feb 8, 2016, and July 27, 2016, 150 participants had viral load testing results for the three assays tested. HCV RNA was detected in 45 (30% [95% CI 23–38]) of 150 participants based on Abbott RealTime. Sensitivity of the Xpert HCV Viral Load assay for HCV RNA detection in plasma collected by venepuncture was 100·0% (95% CI 92·0–100·0) and specificity was 99·1% (95% CI 94·9–100·0). Sensitivity of the Xpert HCV Viral Load assay for HCV RNA detection in samples collected by finger-stick was 95·5% (95% CI 84·5–99·4) and specificity was 98·1% (95% CI 93·4–99·8). No adverse events caused by the index test or the reference standard were observed.

Implications

The Xpert HCV Viral Load test can detect active infection from a finger-stick sample, which represents an advance over antibody-based tests that only indicate past or previous exposure.

Funding

National Health and Medical Research Council (Australia), Cepheid, South Eastern Sydney Local Health District (Australia), and Merck Sharp & Dohme (Australia).

Introduction

Despite a growing burden of hepatitis C virus (HCV) infection worldwide,1, 2 testing and diagnosis remain inadequate.3, 4, 5 As highlighted by the 2016 WHO guidance on HCV testing,⁶ strategies to improve testing and diagnosis of HCV infection are essential to improve linkage to HCV care and treatment with direct-acting antivirals (DAAs).

Strategies to improve HCV testing and diagnosis include on-site HCV testing (via venepuncture),7, 8, 9, 10, 11, 12 dried blood spot testing,7, 12, 13, 14, 15, 16, 17 and point-of-care HCV testing.18, 19, 20 Dried blood spot testing from whole blood collected via finger-stick (also referred to as capillary testing) can enhance HCV testing,6, 12 but requires specialised testing to be done at centralised diagnostic laboratories and people to return for a second visit to receive their result, which is a potential barrier in remote areas and in marginalised populations. Finger-stick21, 22, 23, 24 or oral fluid22, 23, 24, 25 rapid diagnostic HCV tests are available, but many of these tests are restricted—ie, they only measure HCV antibodies (previous exposure), not HCV RNA (active infection).⁶ Given that 25% of individuals spontaneously clear HCV infection,²⁶ efforts to enhance diagnosis of chronic HCV infection and improve the HCV care cascade requires enhanced uptake of HCV RNA testing. Point-of-care HCV RNA platforms enabling detection of HCV RNA and diagnosis of active infection in a single visit would be important for clinical use. As highlighted in the WHO guidance on HCV testing,⁶ nucleic acid tests to detect HCV RNA that can be used at or near the point of care have become commercially available, and could improve access to early diagnosis, monitoring, and linkage to care and treatment services. However, no previous evaluation of a finger-stick HCV RNA point-of-care test has been published.

In this study, we aimed to establish the sensitivity and specificity of the Xpert HCV Viral Load point-of-care test for detection of HCV RNA by plasma samples collected by venepuncture and capillary whole-blood samples collected by finger-stick in participants attending drug health and homelessness services in Australia.

Section snippets

Study design and participants

LiveRLife is an open observational cohort study evaluating the effectiveness of an intervention integrating non-invasive liver disease screening on HCV assessment and treatment uptake.²⁷ Participants were enrolled at five sites in Australia (three drug and alcohol clinics, one homelessness service, and one needle and syringe programme). The detailed study protocol is provided in the appendix.

Research in context

Evidence before this study

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Results

Of 210 participants enrolled between Feb 8, 2016, and July 27, 2016, two participants were excluded because they did not have a finger-stick capillary whole-blood or plasma sample available (figure 1). Of 208 participants with an available sample, 208 participants had capillary whole-blood samples collected via finger-stick and 184 participants had plasma samples collected via venepuncture (Figure 1, Figure 2). Only the 158 participants who had samples available for all three assays were

Discussion

In this study, we showed good sensitivity and specificity of the Xpert HCV Viral Load test for HCV RNA detection in capillary whole blood collected by finger-stick and plasma collected by venepuncture compared with the Abbott RealTime HCV Viral Load RNA assay in people attending drug health and homelessness services in Australia. The major advance of this point-of-care assay over previous antibody tests, which only indicate HCV exposure, is the ability to detect active HCV infection. These

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Blood samples from 158 high–risk individuals were assessed using three different methods at baseline. Results were checked for normality and log transformed. Log differences and bias between methods were calculated and correlated. Pearson's correlation coefficient was used to determine the association of HCV viral loads across all methods. The level of agreement with the standard method (Roche real time HCV) was assessed using Bland–Altman analyses.
There was a strong positive correlation coefficient between all three methods with GeneXpert and Roche having the strongest, r = 0.96, (p<0.001). Compared to Roche, ABL (mean difference, 95 % limits of agreement; -0.063 and -1.4 to 1.3 Log10IU/mL) and GeneXpert (mean difference, 95 % limits of agreement; -0.28 and -0.7 to 1.8 Log10IU/mL) showed a good level of agreement with the GeneXpert being slightly superior.
We demonstrate the excellent performance and no-inferiority, in terms of levels of agreements of both GeneXpert and ABL compared to the Roche platform and supporting the use of the POC assays as alternative a cost-effective methods in HCV detection and diagnosis in developing and low resource settings countries.
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To achieve hepatitis C virus (HCV) elimination targets, simplified care engaging people who inject drugs is required. We evaluated whether fingerstick HCV RNA point-of-care testing (PoCT) increased the proportion of clients attending a supervised injecting facility who were tested for hepatitis C.
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Point-of-care testing for hepatitis C virus (HCV) in high-risk populations is key to diagnosing and eliminating HCV. We aimed to test all occupants for HCV in an entire prison.
All consenting participants at the Brisbane Women’s Correctional Centre were tested for HCV over 3 days using fingerstick samples. Participants with HCV were linked to care by a Nurse Practitioner experienced in HCV management.
211 of 244 participants of the prison population at the time (86%) consented and were tested. 17 participants (8%) had HCV, of who 14 commenced antiviral therapy ≤1 week of testing, 1 was later approved for antiviral therapy in consultation with a physician, and 2 due for release were followed-up and linked to care in the community. Education and counselling provided before testing was rated as very good or excellent by 47% of participants.
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Point-of-care testing for HCV in prisons with dedicated clinicians, resources, and partnerships, particularly at prison entry, can contribute to eliminating HCV in Australia by 2030.
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A total of 540 male participants were enrolled. Median age (29 vs. 28 years) and history of injecting drug use (48% vs. 42%) were similar between standard of care and intervention phases. Among people diagnosed with current HCV infection (n = 18/63 in the standard of care phase vs. n = 30/298 in the intervention phase), the proportion initiating direct-acting antiviral treatment within 12 weeks from enrolment in the intervention phase was higher (93% [95% CI 0.78–0.99] vs. 22% [95% CI 0.64–0.48]; p <0.001), and the median time to treatment initiation was shorter (6 days [IQR 5–7] vs. 99 days [IQR 57–127]; p <0.001) compared to standard of care.
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ArticlesEvaluation of the Xpert HCV Viral Load point-of-care assay from venepuncture-collected and finger-stick capillary whole-blood samples: a cohort study

Summary

Background

Methods

Findings

Implications

Funding

Introduction

Section snippets

Study design and participants

Results

Discussion

J Hepatol

Lancet Infect Dis

Int J Drug Policy

J Hepatol

Int J Drug Policy

J Clin Virol

Int J Drug Policy

Diagn Microbiol Infect Dis

J Clin Virol

Epidemiology and natural history of HCV infection

Nat Rev Gastroenterol Hepatol

Global prevalence and genotype distribution of hepatitis C virus infection in 2015: a modelling study

Lancet Gastroenterol Hepatol

Historical epidemiology of hepatitis C virus (HCV) in select countries—volume 2

J Viral Hepat

Historical epidemiology of hepatitis C virus (HCV) in select countries—volume 3

J Viral Hepat

Historical epidemiology of hepatitis C virus (HCV) in selected countries

J Viral Hepat

Hepatitis C infection among injecting drug users in general practice: a cluster randomised controlled trial of clinical guidelines' implementation

Br J Gen Pract

Articles
Evaluation of the Xpert HCV Viral Load point-of-care assay from venepuncture-collected and finger-stick capillary whole-blood samples: a cohort study