Amoxicillin efficacious for treating syphilis in people with HIV, small study shows

In people living with HIV (PLWH) who also have syphilis, amoxicillin plus probenecid was equally efficacious as low-dose amoxicillin, according to results from a study conducted in Japan. Both regimens showed similar cure rates to standard penicillin injections for syphilis treatment.

About This Study

“Combination of Amoxicillin 3,000 mg and Probenecid versus 1,500 mg Amoxicillin Monotherapy for Treating Syphilis in Patients with HIV: an Open-Label, Randomized, Controlled, Non-Inferiority Trial” was published online on May 9, 2023, in Clinical Infectious Diseases. The lead authors are Naokatsu Ando, B.Med., and Daisuke Mizushima, M.D., Ph.D., of the AIDS Clinical Center at the National Center for Global Health and Medicine in Tokyo, Japan.

Key Research Findings

This randomized controlled trial compared two alternative syphilis treatments for PLWH: 1,500 mg of amoxicillin, which is used in Japan, versus 3,000 mg amoxicillin plus 750 mg probenecid, which is used in the United Kingdom. Standard syphilis treatment is intramuscular benzathine penicillin G.

One hundred twelve PLWH (all men, 97% Asian) from a single site in Tokyo, Japan, were randomized 1:1 to the two regimens. Both patient and treating physician were aware of the allocation. Most participants had early syphilis, mainly secondary syphilis. The study was conducted from 2018-2022, with four participants missing visits due to COVID-19 pandemic-related measures.

Twelve months after treatment, serological cure rates were comparable to those achieved with standard treatment–91% of participants on monotherapy and 94% of participants in the combination arm–were cured. While the difference between the arms was small, both regimens were comparable in efficacy to intramuscular benzathine penicillin G.

Drug-related side effects were somewhat lower in the monotherapy compared to the dual therapy arm (18% vs. 25% of participants, respectively), however, there were no significant differences in the incidence of side effects between the two groups. The most common side effects were Jarisch-Herxheimer reactions (systemic reactions such as fever, rashes, or myalgia within 2 days of starting treatment), as well as nausea and diarrhea. The rate of Jarisch-Herxheimer (13% and 14% of participants, respectively, in the two arms) was significantly lower than that among PLWH with early syphilis on penicillin treatment.

Discussion Highlights and Implications for Practice

The researchers pointed out one limitation was that the study population included only patients with HIV infection, who may have a poor response to treatment of syphilis overall. In addition, some participants missed visits due to the COVID-19 pandemic.

Results show that amoxicillin may be a viable alternative to penicillin with fewer side effects when treating syphilis in PLWH, the authors said. However, they also pointed out that the observed difference in cure rates between the amoxicillin regimens may be related to the small sample size. Larger studies are needed, since even a small difference in efficacy could be important during, e.g., a syphilis epidemic. Studies that directly compare amoxicillin to penicillin are also needed.

By Barbara Jungwirth