Is three really what we need? Relative effectiveness of benzathine penicillin G and doxycycline treatment regimens for late or unknown duration syphilis in 6 United States jurisdictions, 2016-2021.

Abstract

Little evidence supports the need for 3 weekly benzathine penicillin G (BPG) injections to treat late or unknown duration syphilis, and completion of the regimen may be difficult. We compared treatment effectiveness of 1 versus 3 doses of BPG and doxycycline. We conducted a retrospective cohort study using surveillance data for male and female cases diagnosed with late or unknown duration syphilis between 2016 and 2021 from 6 jurisdictions. We categorized BPG and doxycycline treatment based on the recorded number of doses received and the timing between doses. We defined treatment effectiveness as a fourfold decrease in non-treponemal serum titer by 24 months post-treatment and compared treatment effectiveness using log binomial regression. Among 18,027 cases eligible for inclusion, over half had 3 doses of BPG recorded (11,342, 63%); relatively few had only 1 dose recorded (1,928, 11%) or received at least 28 days of doxycycline (3,017, 17%). Fourfold titer decreases were observed for 75% and 80% of cases given 3 doses and 1 dose of BPG, respectively, and for the 74% given doxycycline. Treatment effectiveness was similar across all treatment dose/interval categories and remained comparable when stratified by baseline titer, pregnancy status, and HIV infection. We did not observe a difference in treatment effectiveness between 1 versus 3 doses of BPG, or between 3 doses of BPG and doxycycline, for late or unknown duration syphilis. Additional observational and clinical studies with more complete treatment and serologic response information are needed to confirm these findings and inform practice recommendations.