This study investigates the possible association between the expansion of Pre-Exposure Prophylaxis (PrEP) use and the increase in syphilis cases in Brazil. PrEP is an HIV prevention strategy based on antiretroviral use. Despite its effectiveness against HIV, research suggests that PrEP use may lead to changes in sexual behaviors, such as reduced condom use, which could favor the spread of other sexually transmitted infections (STIs).

To examine, using statistical methods, the relationship between PrEP dissemination and acquired syphilis incidence, using data extracted from the Notifiable Diseases Information System (SINAN) and from the Department of HIV/AIDS, Tuberculosis, Viral Hepatitis and STIs (DATHI), covering 2010 to 2023.

Time series of acquired syphilis notifications and the number of PrEP users were analyzed across the country’s macroregions. Statistical analyses included linear regressions to identify trends (Excel) and correlation tests according to data distribution assessed by the Shapiro–Wilk test, using the JASP analysis tool.

The results showed an increase confirmed by upward linear regression trends in both the number of PrEP users and syphilis incidence for each Brazilian region. Only the Northeast macroregion had a non-normal distribution; therefore, Spearman’s correlation test was applied. For regions with normally distributed data, Pearson’s correlation test was used. All historical series were statistically significant (p < 0.001) with high correlation coefficients: South (r = 0.779), Southeast (r = 0.840), Central-West (r = 0.851), Northeast (ρ = 0.879), and North (r = 0.898). According to the Ramsay scale, all correlations were strong.

The statistical analyses indicated a strong correlation between the growth of PrEP use and the increase in syphilis cases in Brazil. Nevertheless, a direct cause-and-effect relationship cannot be established. Factors such as user profiles, behavioral changes, and more frequent testing may explain the findings. The study suggests the need for further research to clarify this potential causal relationship.