Aim: Syphilis co-infection in HIV-infected patients is associated by a delayed serological response. The aim of this study is to obtain current data on the frequency of HIV/syphilis co-infection, the monitoring of rapid plasma reagin (RPR) titer after treatment, and factors affecting the serologic response. Methods: Serological tests for syphilis of HIV patients followed between January 2015 and March 2023 were evaluated retrospectively. Demografic data (age, sex), level of HIV RNA, RPR, Treponema pallidum haemagglutination test (TPHA), and syphilis stage were obtained from hospital electronic database. Serological response was defined according to Centers for Disease Control and Prevention (CDC) criteria. Results: Syphilis co-infection was detected in 36.2% of the patients, all of them were male. Distribution of syphilis stage was primary 2.9%, secondary 9.7%, latent 80.6%, and neurosyphilis 6.8%, respectively. All patients with primary, secondary, and neurosyphilis had ≥4-fold decrease in RPR titer within 12 months after treatment, while two patients with latent syphilis didn’t have a decrease in titer within 12-24 months. Overall serologic response was 95.8%. Comparing the time to a 4-fold decrease in the RPR titer in terms of syphilis stage, there was no statistically significant difference. Patients with initial RPR titer >1: 32 achieved faster serologic response than those with initial RPR titer ≤1: 32. Conclusion: HIV/syphilis coinfection rate was notably high. It is promising that most patients had a serologic response within the time-frame defined by the CDC. It should be considered that treatment response may take longer in patients with an initial RPR titer ≤32. Further prospective studies are needed to understand the factors associated with serologic response in HIV/syphilis co-infected patients.