Differential effects of primary and latent syphilis co-infection on immune reconstitution and virological failure in HIV-positive adults on ART

HIV and syphilis are sexually transmitted diseases (STDs) that share transmission routes and risks factors. Many countries face the dual challenge of HIV and syphilis epidemics. Co-infection can mutually accelerate disease progression and increase transmission risk, posing a major challenge to global public health. This retrospective study was based on a cohort of people living with HIV (PLWH). All PLWH diagnosed between 2016 and 2023 were included. The Chi-square test was used to compare demographic and clinical characteristics between groups. Factors associated with syphilis co-infection were assessed using multivariate logistic regression, with adjusted odds ratio (aOR) and 95% confidence interval (95%CI) estimated. Kaplan-Meier analysis was used to estimate the cumulative probability of immune reconstitution (IR) and virological failure (VF) in syphilis co-infection versus HIV mono-infected individuals. Multivariate Cox regression was used to evaluate adjusted hazard ratio (aHR) and 95% CI for factors associated with IR and VF. To reduce potential confounding, we used propensity score matching (PSM) to balance baseline covariates between the syphilis co-infection and HIV mono-infection groups. All statistical analyses were performed by SPSS 23.0 and R 4.3.3. Among 39,924 PLWH in Jiangsu Province (2016–2023), the prevalence of syphilis co-infection was 14.1% (5,645/39,924). Factors independently associated with higher odds of co-infection included age < 60 years, male sex, current HIV stage, single, Han ethnicity, history of STDs, and homosexual HIV transmission. In the IR analysis, 56.6% of PLWH achieved IR. After stratifying by syphilis stage, primary syphilis was associated with a higher probability of IR before matching (log rank P < 0.001), but this difference disappeared after PSM (log rank P = 0.99). Latent syphilis showed no significant association with IR. In the virological failure (VF) analysis, latent syphilis co-infection was associated with an increased risk of VF in Cox regression models both before (log rank P = 0.0011) and after PSM (log rank P = 0.0032). Primary syphilis had no significant effect on VF. Younger age at ART initiation, early HIV stage, higher baseline CD4 + T cell count, and college or higher education were protective against VF and/or promoted IR. HIV/syphilis co-infection prevalence was high among PLWH in Jiangsu. Latent syphilis co-infection independently increases the risk of VF. Younger age at ART initiation, current HIV stage, and higher education protected against VF and/or promoted IR; male, migrant, and homosexual HIV transmission were risk factors for poorer IR. Integrated screening and management of syphilis are essential to optimizing HIV treatment outcomes.