Post-treatment serologic, cerebrospinal fluid, MRI, and salivary antibody responses in HIV-negative neurosyphilis: a retrospective study

Objectives This study aimed to characterize longitudinal serologic, cerebrospinal fluid (CSF), MRI, and salivary antibody responses after treatment in HIV-negative neurosyphilis. Methods We retrospectively analyzed 73 HIV-negative adults treated for neurosyphilis from June 2021 to June 2025. Survival endpoints were defined as time to first documented serologic response or CSF normalization. Paired baseline and 12-month saliva samples were available for 25 patients. Cox models were exploratory, and longitudinal MRI findings were analyzed descriptively. Results Among 25 patients with paired saliva samples, salivary antibody OD decreased at 12 months (estimated paired decrease, 0.36 OD units; 95% CI, 0.14–0.64) and showed a modest correlation with the decline in serum TRUST titer (Spearman ρ = 0.396). Of 73 patients, 36 achieved a first documented serologic response. Higher baseline serum TRUST titer was associated with earlier documented response (adjusted HR per twofold increase, 1.34; 95% CI, 1.11–1.61), whereas elevated CSF protein was associated with later documented response (adjusted HR, 0.41; 95% CI, 0.20–0.86). Median times to first documented normalization were 12 months for CSF TRUST, 13 months for CSF WBC, and 20 months for CSF protein; these estimates were derived from separate endpoint-specific risk sets. Follow-up MRI findings in 13 clinically selected patients were descriptive. Conclusion The post-treatment decline in salivary anti- T. pallidum antibody OD provides a preliminary non-invasive signal of treatment-associated change. Prospective validation in larger cohorts is required.