Longitudinal quantitative treponemal-specific immunoassay patterns in syphilis reinfection among MSM living with HIV

Syphilis reinfection is increasing among men who have sex with men (MSM) living with HIV and is frequently asymptomatic, complicating timely diagnosis and management. Current screening strategies rely on multistep serological algorithms that require confirmation with non-treponemal testing, often delaying clinical decision-making. The chemiluminescent microparticle immunoassay for Treponema pallidum (TP-CMIA) is widely used as an initial screening assay and provides quantitative signal-to-cut-off values; however, it is currently designated for qualitative interpretation. We aimed to evaluate whether longitudinal changes (ie, dynamics) in TP-CMIA values can serve as an early marker of syphilis reinfection and support initial clinical decision-making.

We conducted a retrospective observational study including 179 MSM living with HIV who underwent routine syphilis screening between 2014 and 2024 and had at least two paired treponemal (TP-CMIA) and non-treponemal (rapid plasma reagin (RPR)) test results. Syphilis infection status was classified using an algorithm based on RPR dynamics and Centres for Disease Control guidelines. Absolute and relative changes were analysed between sequential tests. Diagnostic performance was assessed using receiver operating characteristic and precision-recall analyses.

Absolute changes in TP-CMIA values demonstrated good diagnostic performance for identifying reinfection, with a receiver operating characteristic area under the curve of 0.84. Performance improved to 0.90-0.95 for first reinfection episodes when prior TP-CMIA values were <21 signal-to-cut-off. Optimised thresholds yielded positive predictive values of 70%-75%, specificity of 99%, and negative predictive values exceeding 98%. Sensitivity increased from 47% overall to 60%-75% under refined conditions. Performance was independent of HIV viral load and CD4 count, while younger age was associated with higher false-positive rates.

Longitudinal absolute changes in TP-CMIA values represent a robust early marker of syphilis reinfection among MSM living with HIV, although it is limited when baseline values are high. TP-CMIA dynamics may support earlier recognition of reinfection and inform initial clinical decision-making during serological follow-up.