Sensitivity and Specificity of Rapid Diagnostic Tests for Hepatitis C Virus With or Without HIV Coinfection: A Multicentre Laboratory Evaluation Study

Abstract

<jats:title>Abstract</jats:title> <jats:sec> <jats:title>Background</jats:title> <jats:p>Hepatitis C virus (HCV) screening is critical to HCV elimination efforts. Simplified diagnostics are required for low-resource settings and difficult-to-reach populations. This retrospective study assessed performance of rapid diagnostic tests (RDTs) for detection of HCV antibodies.</jats:p> </jats:sec> <jats:sec> <jats:title>Methods</jats:title> <jats:p>Two lots of 13 RDTs were evaluated at three laboratories using archived plasma samples from four countries (Nigeria, Georgia, Cambodia, Belgium). HCV status was determined using three reference tests according to a composite algorithm. Sensitivity and specificity were evaluated in HIV infected and HIV uninfected populations. Operational characteristics were also assessed.</jats:p> </jats:sec> <jats:sec> <jats:title>Results</jats:title> <jats:p>In total, 1,710 samples met inclusion criteria. In HIV uninfected samples (n=384), the majority of RDTs had sensitivity ≥98% in one or both lots and most RDTs had specificity ≥99%. In HIV infected samples (n=264), specificity remained high, but sensitivity was markedly lower than in HIV uninfected samples; only one RDT reached &amp;gt;95%. The majority of HIV infected samples for which sensitivity was low did not have detectable HCV viral load/core antigen. Inter-reader variability, lot-to-lot variability and rate of invalid runs were low for all RDTs (&amp;lt;2%).</jats:p> </jats:sec> <jats:sec> <jats:title>Conclusion</jats:title> <jats:p>HCV RDTs should be evaluated in the intended target population, as sensitivity can be impacted by population factors such as HIV status.</jats:p> </jats:sec>

Sensitivity and specificity of rapid hepatitis C antibody assays in freshly collected whole blood, plasma and serum samples: A multicentre prospective study

“…Beijing, China) and the First Response HCV card test (Premier Medical Corporation Ltd., Mumbai, India). Operational characteristics of these tests are shown in S1 Table. These RDTs were selected as they met WHO prequalification criteria in archived plasma samples in the previous study [7], and the manufacturers had demonstrated a commitment to seeking WHO prequalification status.…”

“…RDTs were tested on three sample types: fingerstick whole blood, ethylenediaminetetraacetic acid (EDTA) plasma, and serum (matched samples), all collected and tested on the same day. Performance was compared with three WHO prequalified laboratory reference tests, of which two were enzyme immunoassays (EIAs; Murex Anti-HCV version 4.0, Fujirebio INNOTEST HCV Ab IV) and one was a line immunoassay (LIA; Fujirebio INNO-LIA HCV Score), using a previously described composite reference standard (CRS) that incorporated the results of all three reference tests [7]. The algorithm was based on WHO prequalification evaluation protocols, with the final decision being based on the LIA test result.…”

“…However, using these assumptions, the minimum sample sizes to achieve 80% power with a 95% CI of ±5% were lower than WHO Technical Specification Series-7 (TSS-7) requirements of 400 HCV positive and 1000 HCV antibody and RNA negative samples for diagnostic assessments of HCV RDTs [4]. Therefore, the TSS-7 values were used, with a 10% increase to account for sample exclusion due to indeterminate HCV status with the CRS (based on experience from the previous study [7]). Final sample size targets were 440 HCV antibody positive (HCV positive) and 1,100 HCV antibody negative (HCV negative) samples.…”

“…Nevertheless, HCV screening programmes using these RDTs must take into account the potential for lower performance in whole blood in real-world versus laboratory settings, particularly given that testing of fingerstick blood in non-laboratory settings is likely to be a common usage of these tests. In our previous study using archived plasma samples [7], sensitivity of the investigational RDTs met the WHO prequalification sensitivity criterion of �98% [8], when compared with the laboratory-based CRS. In the current study, this criterion was narrowly missed by both RDTs in serum, and one of two in plasma.…”

“…A previous retrospective study evaluated the performance of 13 HCV RDTs in archived plasma samples [7]. In this study, the majority of RDTs exhibited performance in line with WHO criteria for selection of HCV diagnostics in samples from patients without human immunodeficiency virus [HIV] co-infection (sensitivity �98% and specificity of �97% in serum or plasma samples [8,9]).…”