Doxycycline vs. penicillin G benzathine for the treatment of syphilis in patients with HIV

Background: Syphilis is a highly prevalent sexually transmitted infection which can lead to serious health complications if not treated effectively. Historically, penicillin G benzathine has been the primary agent used to treat syphilis infections, with doxycycline being an alternative agent for patients who cannot tolerate penicillin antibiotics. The efficacy of doxycycline in treating syphilis in patients with HIV, however, has not been well documented despite its use as an alternative treatment. The objective of this study is to compare the ability of these two agents to treat syphilis, specifically in patients infected with human immunodeficiency virus (HIV).

Methods: This study has been approved by the facility’s Institutional Review Board. It examined a cohort of patients retrospectively to analyze the comparative effectiveness of resolution of syphilis infection in patients treated with penicillin G benzathine vs. doxycycline utilizing diagnosis codes for specific types of syphilis (primary, secondary, tertiary, early latent, late latent). An information technology specialist working with the institution was instructed to run a report of patients from the electronic medical record who received a prescription for doxycycline or were administered an intramuscular injection of penicillin G benzathine with a diagnosis for syphilis and HIV. The population of patients was collected from October 2020 to present. An informational technology specialist developed the report and pulled any identifiable patient information prior to forwarding to the primary research team. Clinical pharmacy residents reviewed all patients included in the report for involvement in the study based on set inclusion and exclusion criteria. The primary endpoint assessed was resolution of syphilis infection, with secondary endpoints looking at reported adverse reactions to treatment, reinfection with syphilis, and incomplete initial treatment. All members of the research team were kept up to date on the happenings of the trial, as is relevant for their level of involvement.

Results: Data analysis for this trial is still ongoing. The total number of patients included in the study was 134, with 21 patients having received doxycycline and 113 having been administered penicillin G benzathine. The primary outcome occurred in 18/21 (85.71%) of patients in the doxycycline arm, while 103/113 (91.15%) of patients in the penicillin group saw resolution of syphilis. Adverse effects were widely unreported, with gastrointestinal symptoms being the only type of reaction reported. One patient reported diarrhea after taking doxycycline, and another patient reported nausea after receiving an injection of penicillin G benzathine.

Conclusion: Doxycycline had a lower resolution of infection. This could be due to the uneven distribution of patients between the two arms of the study. Given that the place in therapy of doxycycline is primarily patients with severe penicillin allergy, it is not surprising that far more patients were treated with penicillin G benzathine than with doxycycline. The lack of reported adverse effects is encouraging, as it is likely they would have been stated if reactions had occurred. Other endpoints will be analyzed in the future. Further, larger scale, studies are needed to determine if doxycycline is truly inferior to penicillin in treating syphilis infection.