Syphilis in people living with HIV

Syphilis and HIV are two closely intertwined sexually transmitted infections, with bidirectional effects on transmission, clinical manifestations, and immunopathogenesis. People living with HIV (PLWH) are at higher risk of syphilis acquisition and reinfection, while syphilis may increase susceptibility to HIV acquisition and has been associated with transient changes in HIV virological and immunological parameters. In PLWH, syphilis can present with a broad spectrum of clinical manifestations, including atypical, severe, or multisystemic presentations such as neurologic, ocular, and malignant forms, although the frequency and clinical significance of these manifestations in routine practice remain uncertain. Serological diagnosis can be challenging due to delayed seroconversion, false-negative results, and slower declines in non-treponemal antibody titers. Although penicillin-based therapy remains the mainstay of treatment, PLWH require careful clinical and serological monitoring because of the potential for inadequate serologic responses and frequent reinfections, particularly in populations at increased risk. Emerging strategies, such as post-exposure prophylaxis with doxycycline, may benefit selected high-risk populations, although evidence remains limited for some groups. Understanding the complex interplay between HIV and syphilis is essential to optimizing diagnosis, management, treatment, and prevention.