Comparative effectiveness of three benzathine penicillin G-based regimens in people with HIV who presented with early...

To compare 12-month serologic responses to three benzathine penicillin G (BPG)-based regimens among people with HIV (PWH) and early syphilis.

We retrospectively included syphilis episodes treated with BPG, BPG plus 7-day doxycycline (BPG/doxycycline), or BPG/doxycycline plus single-dose ceftriaxone during 2018-2024. Episodes with baseline rapid plasma reagin (RPR) titers <1:4 or exposure to other Treponema pallidum-active antibiotics were excluded. Serologic response was defined as a ≥ 4-fold RPR decline at 12 months. Intention-to-treat (ITT) with last-observation-carried-forward and per-protocol analyses were performed.

Among 1077 episodes in 762 PWH, 453 received BPG, 570 BPG/doxycycline, and 54 BPG/doxycycline/ceftriaxone. ITT response rates were 74.6%, 83.2%, and 88.9%, respectively (P < 0.001); per-protocol rates were 74.4%, 83.4%, and 89.8% (P < 0.001). Higher baseline RPR titers and doxycycline-containing regimens were independently associated with response. In analyses directly comparing BPG/doxycycline with and without ceftriaxone, adding ceftriaxone to BPG/doxycycline was not significantly associated with a higher serologic response.

BPG/doxycycline was associated with a higher likelihood of 12-month serologic response. The incremental association of ceftriaxone remained uncertain because of the small number of ceftriaxone-treated episodes.