Optical biosensor platforms for rapid and ultrasensitive detection of HIV-1 p24 antigen

Human immunodeficiency virus (HIV) infection remains a major global health challenge an estimated 40.8 million people were living with HIV and approximately 1.3 million new infections occurred worldwide in 2024 (UNAIDS/WHO estimates). Early and accurate diagnosis, particularly during the acute “diagnostic window” phase of infection, is critical for timely therapeutic intervention and prevention of transmission. Conventional diagnostic methods, including enzyme-linked immunosorbent assays (ELISA), Western blotting, and nucleic acid amplification tests (NAATs), remain limited by multi-step protocols, assay times of hours to a day, dependence on centralized laboratory infrastructure, and reduced sensitivity during early infection, when the p24 capsid antigen is the dominant circulating biomarker. Recent advances in nanobiosensor technology have enabled highly sensitive and rapid diagnostic platforms for p24 detection. Among these, optical biosensors based on gold nanoparticles (AuNPs) have attracted considerable attention because of their localized surface plasmon resonance (LSPR) properties, which enhance optical signal transduction and amplification. Depending on the transduction mode (colorimetric, fluorescence, SERS, or SPR/LSPR), reported analytical performance spans limits of detection (LOD) from the pg/mL to attomolar/femtomolar range, with assay times typically between 10 and 60 min-parameters that are summarized comparatively across platforms in this review, alongside bioreceptor type, linear range, sample matrix, and point-of-care (PoC) suitability. This review provides a comprehensive and critical overview of optical and AuNP-based nanobiosensor platforms for HIV-1 p24 antigen detection. Key design strategies, sensing mechanisms, analytical performance, and clinical applicability are discussed, and electrochemical, piezoelectric, thermometric, magnetic, and FET-based platforms are included as comparator technologies to contextualize the performance of optical systems. Current challenges related to assay standardization, reproducibility, batch-to-batch variability, long-term stability, large-scale manufacturability, and validation against real clinical specimens (serum, plasma, whole blood) are critically examined. By consolidating scattered literature into a single comparative framework and explicitly linking analytical LODs to the clinically relevant concentration range of p24 in early infection, this review is intended to guide the rational design and clinical translation of next-generation, rapid, ultrasensitive, and accessible HIV diagnostic platforms for resource-limited settings.