Comparison of 3 Treatment Regimens for Latent Syphilis of Late or Unknown Duration Using Public Health Surveillance Data
Travis J. Hunt, Anna Berzkalns, Chase A. Cannon, Timothy W. Menza, Julia C. Dombrowski, Matthew R. Golden
Abstract
BACKGROUND: The Centers for Disease Control and Prevention recommends treating latent syphilis of late/unknown duration (LSUD) with 3 doses of intramuscular benzathine penicillin G (BPG) or 28 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 reactive plasma reagin [RPR] decline) among persons with LSUD following receipt of 1 of 3 regimens: 1 dose of BPG, 3 doses of BPG, and 28 days of doxycycline. Subjects included persons diagnosed in 2007 to 2020 with an initial RPR ≥1:2 and follow-up RPR testing 1 to 36 months after 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 (interquartile range, 114-488 days). Among high-titer persons, serological cure occurred in 36 of 41 (88%), 330 of 376 (88%), and 58 of 64 (88%) receiving single-dose BPG, 3-dose BPG, and doxycycline, respectively. Among low-titer persons, serological cure occurred in 4 of 13 (31%), 114 of 235 (49%), and 14 of 30 (47%) receiving single-dose BPG, 3-dose BPG, and doxycycline, respectively. Controlling for initial RPR, serological cure did not differ between high-titer persons receiving 1- and 3-dose BPG (adjusted hazard ratio, 0.89; 95% confidence interval, 0.63-1.26) or 1-dose BPG and 28 days of doxycycline (adjusted hazard ratio, 1.03; 95% confidence interval, 0.68-1.58). CONCLUSIONS: Serological outcomes in high-titer LSUD after 1 dose of BPG, 3 doses of BPG, and 28 days of doxycycline are similar.