Acquired syphilis in the context of pre-exposure prophylaxis for HIV: a systematic review of the scientific literature

The aim of this study was systematically review the acquired syphilis before and during follow-up of pre-exposure prophylaxis (PrEP) for HIV. We analyzed articles that studied PrEP users with the outcome of acquired syphilis. The eligibility criteria were studies retrieved from the United States National Library of Medicine (Pubmed), Latin American and Caribbean Health Sciences Literature (Lilacs), Embase and Scopus databases, published between 2012 and 2023, in English, Spanish or Portuguese. We performed the descriptive synthesis and quality analysis of selected studies using the Newcastle Ottawa scale or Cochrane scale. We also used random-effects models to generate pooled rate estimates for syphilis before PrEP and during follow-up. A total of 4412 studies were found and 35 were selected, all in English, and almost all with high or satisfactory quality. The review found a PrEP syphilis rate of 6.0%. A summary of three studies estimated a 2.34-fold increased risk of syphilis acquisition during PrEP, with an incidence rate of 8.89 cases/100 person-years. These findings warrant caution due to study heterogeneity. Compared to HIV-positive individuals, PrEP users exhibit potentially higher syphilis rates, particularly among those aged 33-38 years, and factors such as age ≥ 35 years, MSM status, prior sexually-transmitted infections, and longer PrEP duration (every 6 months) are associated. Future research should further investigate these PrEP-related factors contributing to heightened syphilis risk.