False-positive results in fourth-generation HIV screening tests: Prevalence and associated factors in Sichuan, a high HIV burden province of China.

Immunodeficiency virus (HIV) antigen/antibody screening assays are highly sensitive and specific, but false-positive (FP) results remain a challenge. Understanding the prevalence and factors associated with these FP results is crucial, especially in high HIV burden regions. A retrospective cohort study of 370,291 patients screened with the ARCHITECT HIV Ag/Ab Combo assay at a Sichuan tertiary hospital (January 2022-December 2023) was conducted. We calculated HIV prevalence and assessed the test's FP rate, sensitivity, specificity and positive predictive value (PPV). Clinical characteristics and associated disease profiles of individuals with FP results were also analyzed. The overall HIV infection rate was 0.17 %. The FP rate for HIV screening was 0.08 %, with higher incidences observed among females, children (aged 0-17 years), and individuals aged 66 and older (P < 0.001). The mean signal-to-cutoff ratio (S/CO) in true positives (TPs) was significantly higher than that in FPs (576.63 vs. 1.94, P < 0.0001). A receiver operating characteristic (ROC)-determined cutoff of 19.6 provided optimal sensitivity (95.10 %) and specificity (99.99 %). FP results were associated with 18 disease categories, with digestive system disorders being the most prevalent. Malignant tumors, pregnancy, and cerebral infarction were also linked to FPs. These findings highlight the critical need for targeted screening strategies and more precise interpretation protocols to improve diagnostic accuracy. Furthermore, the link between FP results and various non-HIV-related diseases suggests that careful patient characterization may aid in identifying underlying conditions, thereby informing more effective clinical decision-making and public health interventions.