Impact of Syphilis Co-infection on Virological and Immunological Outcomes in People Living with HIV Receiving Long-term Antiretroviral Therapy

Shiyun WangJie Peng^*

• Department of Infectious Diseases, Nanfang Hospital, Southern Medical University, Guangzhou, China

Objective: Syphilis remains a frequent coinfection in people living with HIV (PLWH) and may influence immune recovery during antiretroviral therapy (ART). However, its long-term impact on virological and immunological responses is not fully defined. Method: A retrospective cohort of 614 individuals newly diagnosed with HIV, including 148 with syphilis co-infection, was followed longitudinally for up to 5 years. Virological suppression and immune recovery (IR) were assessed. In a subgroup of 28 patients, peripheral T- and B-cell subset dynamics and cytokine production were analyzed before and after ART. Result: Viral suppression and CD4⁺ T-cell recovery were comparable between groups, although HIV-syphilis coinfection patients exhibited higher CD8⁺ T-cell counts at years 1, 3, and 5. Initially treated syphilis cases achieved higher serological cure rates than repeatedly treated cases (82.5% vs. 60.0%, p = 0.036), whereas recurrence was more frequent in repeatedly treated patients (51.6% vs. 21.9%). During ART, 13.9% of PLWH developed new syphilis infections. Both groups demonstrated ART-associated immune shifts, including reductions in CD8⁺ TEMRA (CCR7⁻ CD45RA⁺) cells, increases in memory B cells (CD27⁺ CD38dim), and decreases in regulatory B cells (CD24⁺ CD38hi). Notably, coinfected patients displayed higher baseline CD4⁺ TEMRA and PD-1 expression. Furthermore, syphilis was associated with Th1 (CD4⁺ CXCR3⁺ CCR6⁻) polarization, elevated CD8⁺ TEM (CCR7⁻ CD45RA⁺), and persistent TNF-α production following ART. Conclusion: Syphilis co-infection alters CD8⁺ T cell dynamics and immune activation profiles in PLWH during ART, despite similar virological outcomes after ART. These findings underscore the need for tailored immune monitoring and syphilis management in co-infected populations.