Comparison of Three Treatment Regimens for Latent Syphilis of Late or Unknown Duration Using Public Health Surveillance Data

Background: The CDC recommends treating latent syphilis of late/unknown duration (LSUD) with three doses of intramuscular benzathine penicillin G (BPG) or twenty-eight days of oral doxycycline. This recommendation lacks high-quality evidence.

Methods: Using public health surveillance data from King County, Washington, we conducted a retrospective cohort study comparing rates of serological cure (>=2-titer RPR decline) among persons with LSUD following receipt of one of three regimens: one dose of BPG, three doses of BPG, and twenty-eight days of doxycycline. Subjects included persons diagnosed 2007-2020 with initial an RPR >=1:2 and follow-up RPR testing 1-36 months post-treatment. We stratified initial RPRs into high- and low-titer (>=1:32, <1:32) and compared outcomes using Cox proportional hazards.

Results: The study population included 761 persons with median time from treatment to last RPR/serological cure of 219 days (IQR 114-488). Among high-titer persons, serological cure occurred in 36 (88%) of 41, 330 (88%) of 376, and 58 (88%) of 64 receiving single-dose BPG, three-dose BPG, and doxycycline, respectively. Among low-titer persons, serological cure occurred in 4 (31%) of 13, 114 (49%) of 235, and 14 (47%) of 30 receiving single-dose BPG, three-dose BPG, and doxycycline, respectively. Controlling for initial RPR, serological cure did not differ between high-titer persons receiving one- and three-dose BPG (aHR: 0.89; 95% CI: [0.63, 1.26]) or one-dose BPG and twenty-eight days of doxycycline (aHR: 1.03; 95% CI: [0.68, 1.58]).

Conclusions: Serological outcomes in high-titer LSUD following one dose of BPG, three doses of BPG, and twenty-eight days of doxycycline are similar.