Single-dose Ceftriaxone Plus 7-Day Doxycycline Versus Single-dose Benzathine Penicillin G Plus 7-Day Doxycycline in the Treatment of Early Syphilis in People With HIV: a Pilot Randomized Noninferiority Trial.

BACKGROUND: Both ceftriaxone (CRO) and doxycycline demonstrate activity against Treponema pallidum and bacteria causing sexually transmitted infections (STIs); however, the efficacy of their combination in a shorter duration remains unclear. We compared single-dose, 1-g CRO plus 7-day doxycycline (CRO/Doxy) with single-dose, 2.4-MU benzathine penicillin G plus 7-day doxycycline (BPG/Doxy) in treating early syphilis among people with HIV (PWH). METHODS: In this pilot randomized clinical trial, eligible participants were randomized to receive CRO/Doxy or BPG/Doxy. Rapid plasma reagin (RPR) titers were determined at baseline and at weeks 4, 12, 24, 36 and 48. PCR assays were conducted at baseline and at week 4 to detect T. pallidum and other STI-causing bacteria in oral rinse, urethral swab, and rectal swab samples to assess microbiologic responses. The primary outcome was the serologic responses of syphilis, defined as a 4-fold or greater decline of RPR titer at week 24. RESULTS: From March 2023 to September 2024, 56 and 53 PWH with early syphilis were randomized to receive CRO/Doxy and BPG/Doxy, respectively. At baseline, 31.2% (n = 34) had chlamydia, 13.8% (n = 15) gonorrhea, and 6.4% (n = 7) Mycoplasma genitalium coinfection. In the ITT analysis, compared to the participants receiving BPG/Doxy, those receiving CRO/Doxy showed a lower serologic response rate at 24 weeks (60.7% vs 75.5%; difference, -14.8 percentage points; 95% CI, -32.0 to 2.5). The microbiologic response rates of syphilis, chlamydia, and M. genitalium infection were comparable between groups. CONCLUSIONS: In the ITT analysis, CRO/Doxy was not noninferior to BPG/Doxy for early syphilis treatment among PWH at 24 weeks.