Syphilis is a sexually transmitted infection for which few treatment alternatives exist beyond penicillin. Although the combination of amoxicillin and probenecid is included in some guidelines as an alternative regimen for syphilis treatment, the use of amoxicillin alone remains poorly studied. We conducted a prospective, multicenter, randomized non-inferiority clinical trial comparing amoxicillin trihydrate (two 875 mg tablets every 12 hours; total 3.5 g/day) for 14 days for early syphilis or 28 days for late syphilis with the standard treatment using benzathine penicillin. Individuals aged ≥ 18 years were recruited in Natal and São Paulo and randomized according to HIV status and stage of syphilis (early or late). Participants were followed every two months with VDRL testing for 6 or 12 months, depending on the stage of syphilis. Exclusion criteria included pregnancy, allergy to penicillin or amoxicillin, tertiary syphilis or neurosyphilis, and silicone implants preventing penicillin injection. Participants with a four-fold (two-dilution) decline in VDRL titer by the end of follow-up were considered to have achieved an adequate treatment response. We present preliminary results for the first 57 participants enrolled up to December 2024 from a planned sample of 120. The mean age was 35.7 years (SD 10.8); 80.7% were men who have sex with men, and 34.5% were living with HIV. Previous syphilis treatment was reported by 54.4%. Latent syphilis was the most common diagnosis (39 patients, 68%; early latent 24 patients, 61.5%), followed by primary (10 patients, 17.5%) and secondary syphilis (8 patients, 14%). Among the 20 participants who completed follow-up, 18 achieved an adequate treatment response (90%). Two treatment failures occurred, both in the early syphilis group—one in the amoxicillin arm and one in the penicillin arm. Both were HIV-negative, reported good adherence, and denied unprotected sex during follow-up; both were subsequently treated with three doses of penicillin and responded well. Self-reported adherence was 96.6% with amoxicillin and 100% with penicillin. The regimen of 3.5 g/day of amoxicillin without probenecid appears effective for the treatment of acquired syphilis in patients with and without HIV, supporting continuation of the study.
Bay et al. (Sun,) studied this question.