Background/Objectives: The Elecsys HCV Duo immunoassay simultaneously detects HCV core antigen (HCV Ag) and anti-HCV antibodies in a single sample. We evaluated its clinical performance against a standard-of-care reference algorithm of anti-HCV antibody and HCV RNA testing. Methods: We retrospectively analyzed 1332 residual serum or plasma samples tested with reference HCV RNA assays and the Alinity i Anti-HCV assay. Samples were classified as reference-positive, indicating current or past HCV infection (n = 166; 88 RNA+/Ab+ with active infection and 78 RNA−/Ab+ with resolved or treated infection), or reference-negative (n = 1166; RNA−/Ab−), including 1000 randomly selected blood donor samples. All specimens were tested with the Elecsys HCV Duo (cobas^® e 801, Roche Diagnostics). Positive and negative percent agreements (PPA and NPA) were calculated against the combined reference standard. Results were further analyzed by infection status and viral load. No HCV RNA+/anti-HCV− (window-period) specimens were available. Results: Overall agreement was high (PPA 98.8% [164/166; 95% CI, 95.7–99.9%]; NPA 99.9% [1165/1166; 95% CI, 99.5–100.0%]). Agreement of the anti-HCV component with the Alinity i Anti-HCV assay was identical (PPA 98.8%, NPA 99.9%). The HCV Duo Ag component showed a PPA of 60.2% (95% CI, 49.2–70.5%) and NPA of 99.0% (95% CI, 98.3–99.5%) against HCV RNA detection. The Ag module was also reactive in 12 of 78 (15.4%) RNA−/Ab+ specimens, all from previously treated patients; thus, 53 of 65 (81.5%) dual Ag/Ab-reactive specimens had detectable HCV RNA. HCV Ag positivity was highest at HCV RNA ≥10⁶ IU/mL (77.4%, 41/53), compared with 32.1% (9/28) at 10⁴–10⁶ IU/mL and 42.9% (3/7) at <10⁴ IU/mL. Receiver operating characteristic analysis of the Ag component yielded an area under the curve of 0.920 (95% CI, 0.904–0.934). Conclusions: The Elecsys HCV Duo demonstrated high overall agreement with the reference methods, supporting its potential as a single-step screening test for HCV infection. Most, but not all, dual Ag/Ab-reactive specimens were viremic, so this result may help prioritize anti-HCV-positive individuals for linkage to care; however, the assay does not replace HCV RNA testing, which remains necessary to confirm active infection, particularly in Ag-negative or previously treated individuals. Because no window-period specimens were included, the potential of the assay for earlier detection of acute infection could not be evaluated.

Background/Objectives: Since the World Health Organization (WHO) recommended HIV self-testing as an alternative to traditional facility-based testing in 2016, it has been increasingly adopted worldwide. This study aimed to evaluate the performance of the ConfiSign HIV Self-Test (GenBody Inc., Republic of Korea), a newly developed blood-based immunochromatographic assay for the qualitative detection of total antibodies (IgG and IgM) against HIV-1/HIV-2. Methods: The evaluation included four components: (1) retrospective analysis of 1400 archived serum samples (400 HIV-positive and 1000 HIV-negative samples), (2) prospective self-testing by 335 participants (112 HIV-positive participants and 223 individuals with an unknown HIV status, including healthy volunteers), (3) assessment using seroconversion panels and diverse HIV subtypes, and (4) analytical specificity testing for cross-reactivity and interference. The Elecsys HIV combi PT and Alinity I HIV Ag/Ab Combo assays were used as reference assays. Results: In retrospective testing, the ConfiSign HIV Self-Test achieved a positive percent agreement (PPA) of 100%, a negative percent agreement (NPA) of 99.2%, and a Cohen’s kappa value of 0.986, showing excellent agreement with the reference assays. In the prospective study, the test showed 100% sensitivity and specificity, with a low invalid result rate of 1.8%. All HIV-positive samples, including those with low signal-to-cutoff (S/Co) values in the Alinity I assay, were correctly identified. The test also reliably detected early seroconversion samples and accurately identified a broad range of HIV-1 subtypes (A, B, C, D, F, G, CRF01_AE, CRF02_AG, and group O) as well as HIV-2. No cross-reactivity or interference was observed with samples that were positive for hepatitis viruses, cytomegalovirus, Epstein–Barr virus, varicella zoster virus, influenza, HTLV-1, HTLV-2, or malaria. Conclusions: The ConfiSign HIV Self-Test demonstrated excellent sensitivity, specificity, and robustness across diverse clinical samples, supporting its reliability and practicality as a self-testing option for HIV-1/2 antibody detection.