Syphilis serological tests are crucial for diagnosing and evaluating syphilis therapy. Human immunodeficiency virus (HIV) infection can alter syphilis serologies, making manifestations more atypical and increasing complications. This study aims to compare treponemal and nontreponemal titers before and after therapy between HIV-positive and negative patients. From January 2018 to December 2021, we retrospectively evaluated patients diagnosed with early and latent syphilis using quantitative nontreponemal and treponemal serologies (VDRL and TPHA) and categorized them as HIV-positive or negative. Baseline and post-therapy (1 month and last follow-up within 2 years) VDRL and TPHA titers were recorded. Twenty-nine HIV-negative and 28 HIV-positive patients met the inclusion criteria. Baseline VDRL and TPHA titers differed significantly between both groups, particularly in early syphilis, with the median baseline VDRL titer higher in the HIV-positive group. At 1-month and the last follow-up after therapy, VDRL titers continued to differ significantly, underscoring the impact of HIV coinfection on treatment response. Notably, TPHA titers exhibited significant differences between the two groups only at the last follow-up in overall syphilis. The HIV-positive group showed a higher percentage of patients failing to achieve a serological cure (60.7% vs. 58.6%). HIV coinfection in syphilis patients affects both nontreponemal and treponemal titers and elevates the treatment failure risk. This study highlights the importance of periodic syphilis serology tests in coinfected individuals to ensure treatment effectiveness, detect reinfection promptly, and prevent complications. [ J Adv Biotechnol Exp Ther 2024; 7(2.000): 442-450]