The Population-Level Impact of Doxycycline Postexposure Prophylaxis on Syphilis in King County, WA: An Interrupted Time Series Analysis

BACKGROUND: An initial evaluation found that doxy-PEP has a population-level effect on syphilis among cisgender men and transgender women who have sex with men. Whether doxy-PEP's impact is generalizable across the U.S. and will affect syphilis incidence among cisgender women and pregnant people - populations who seldom receive doxy-PEP - and congenital syphilis (CS) is unknown. METHODS: We used public health surveillance data from January 2017-June 2025 to conduct an interrupted time series analysis of monthly syphilis diagnoses (all stages) overall and by gender before and after doxy-PEP implementation in March 2023 in King County, WA. We estimated the observed and counterfactual number of syphilis cases post-implementation to calculate absolute and relative differences in cases. RESULTS: In the post-implementation period, the absolute difference in total syphilis cases was -3031 (95%CI:-4295, -1768) with a relative difference of -52.3% (95%CI:-74.1%, -30.5%). Among cisgender men, the absolute difference in cases was -2248 (95%CI:-3321, -1175) for a relative difference of -53.1% (95%CI:-78.5%, -27.8%) in the post-implementation period. Cisgender women experienced an absolute difference of -755 cases (95%CI:-939, -572) and a relative difference of -46.9% (95%CI:-58.3, -35.5%) after doxy-PEP implementation. Among transgender and nonbinary people, the absolute difference in syphilis cases was -56 (95%CI:-90, -23), a relative difference of -33.1% (95%CI:-53.3, -13.6%), in the post-implementation period. Syphilis cases among pregnant persons rose from 13 in 2017 to 48 in 2024 while CS cases increased from 0 in 2017 to 23 in 2024. CONCLUSIONS: After the implementation of doxy-PEP, syphilis diagnoses declined dramatically, including among cisgender women. This decline has not affected syphilis in pregnant persons or CS.