HCV core antigen testing accurately detects acute HCV in patients with HIV

Hepatitis C virus core antigen (HCVcAg) testing accurately identifies acute or recent HCV infection in patients with HIV, according to study findings published in Open Forum Infectious Diseases.

Given delayed antibody responses in individuals with HIV and barriers to nucleic acid amplification test (NAAT) availability in some settings, researchers evaluated whether HCVcAg could reliably detect early infection. They conducted a systematic review and meta-analysis to assess the diagnostic performance of HCVcAg compared with NAATs in patients with HIV with acute or recent HCV infection.

Using PubMed, EMBASE, Scopus, and Web of Science, the researchers searched for studies from January 2000 through May 2024 examining HCVcAg performance in this population. Studies were eligible if they included patients with HIV, used NAATs as the reference standard, and reported data enabling assessment of sensitivity, specificity, true positives, false positives, true negatives, and false negatives. Acute or recent infection was defined as anti-HCV seroconversion within 1 year or positive HCV RNA testing in the absence of antibodies.

The researchers identified 229 articles, 4 of which met inclusion criteria after full-text review. Across these studies, 1015 patients contributed 1796 tests. All studies used the ARCHITECT HCV Ag assay; 3 applied a cutoff of 3 fmol/L and 1 used 10 fmol/L. One study was prospective and 3 were retrospective. Most patients were undergoing routine screening or evaluated due to elevated liver enzymes or recent sexually transmitted infections.

Pooled sensitivity for HCVcAg to detect acute or recent infection was 0.92 (95% CI, 0.78-0.98), and pooled specificity was 0.99 (95% CI, 0.97-1.00). Positive and negative likelihood ratios were 73.54 and 0.08, respectively, supporting strong diagnostic value. Simulation analysis demonstrated a negative predictive value approaching 100%, while positive predictive value varied by underlying incidence but was higher in settings with elevated reinfection risk among patients with HIV.

Across studies, reinfection was reported but not uniformly evaluated for diagnostic accuracy. Heterogeneity was low for sensitivity and moderate to high for specificity and positive likelihood ratio.

Study limitations include the small number of available studies, variability in case definitions and testing pathways, and lack of cost-effectiveness and real-world implementation analyses. Additionally, 1 study shows changes in NAAT platforms during the study period, and follow-up timeframes vary.

According to the researchers, “These findings suggest that the HCVcAg assay may serve as a valuable tool for integration into clinical practice for HCV screening and diagnostic protocols for this high-risk population, facilitating the implementation of the ‘treatment-as-prevention’ strategies for PWH [people with HIV-1].”

Disclosure: This research was supported by the National Taiwan University Hospital and Gilead Sciences. Multiple study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of disclosures.

By Hibah Khaja, PharmD

References:

Tsai T-Y, Chen G-J, Sun H-Y, Hung C-C. HCV core antigen diagnostic performance for acute/recent HCV infection in people with HIV-1: a systematic review and meta-analysis. Open Forum Infect Dis. Published online October 17, 2025. doi:10.1093/ofid/ofaf576