Amoxicillin Monotherapy Shows High Efficacy Against Syphilis in Patients With HIV

Study results published in Clinical Infectious Diseases indicate that low-dose amoxicillin monotherapy is highly efficacious against syphilis in patients with HIV infection.

Researchers conducted an open-label, noninferiority, randomized-controlled trial between August 2018 and February 2022 in Tokyo, Japan. Individuals eligible for inclusion were those aged 20 years and older with syphilis and HIV infection. Patients (n=112) were randomly assigned 1:1 to receive either oral treatment with low-dose amoxicillin (500 mg) or amoxicillin (1000 mg) plus probenecid (750 mg), administered 3-times daily. For patients in both groups, the duration of treatment was 14 days for those with early-stage syphilis and 28 days for those with late-stage syphilis. The primary outcome was the cumulative serologic cure rate within 12 months of treatment initiation, measured via rapid plasma reagin card (RPR) testing. Treatment adherence was determined via self-reporting, and Farrington-Manning testing was used to determine noninferiority for the difference in serologic cure rates between the groups.

Among patients included in the analysis, the median age was 39 (IQR, 31.5-46.5) years, 86.6% had early syphilis, 13.4% had late syphilis, 91.1% were receiving antiretroviral therapy, the median CD4⁺ count was 525/µL, and 94.6% were virologically suppressed. At baseline, the median manual RPR titer was 64 (IQR, 32-128) and the median automated RPR titer was 151.9 (IQR, 58.8-345).

Manual RPR testing showed that serologic cure rates within 12 months were 90.6% and 94.4% among patients in the monotherapy and combination therapy groups, respectively. For patients with early syphilis, 12-month serologic cure rates were 93.5% among those who received monotherapy and 97.9% among those who received combination therapy. For patients with late syphilis, the serologic cure rate was 71.4% among those in both groups at this time.

In regard to noninferiority of cure rates between the groups, manual RPR test results were not statistically significance at any time point. However, at 3 months, both manual and automated RPR testing showed a higher serologic cure rate among patients with early syphilis who received combination therapy vs monotherapy (P =.021).

Of patients who reported treatment-related adverse effects (n=24), 17.9% were in the monotherapy group and 25% were in the combination therapy group (P =.357). In addition, 93.8% of patients reported adherence to more than 95% of the study drug.

Study limitations include the small sample size and the lack of comparison between both treatment regimens and benzathine penicillin G, the standard therapy for syphilis. There also was insufficient power to demonstrate noninferiority between the treatment regimens as 4 patients missed follow-up visits due to the COVID-19 pandemic. Further, as the population included only patients with HIV infection, the efficacy of both regimens may have been underestimated compared with that of their use in those without HIV infection.

These findings “[D]emonstrate a high efficacy of amoxicillin-based regimens for syphilis in patients with HIV infection,” the researchers noted. “[A]moxicillin would be a good alternative to intramuscular benzathine penicillin G with fewer side effects,” the researchers concluded.

Disclosures: Multiple study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the reference for a full list of authors’ disclosures.