Sexually transmitted infection syndemic interactions: Biological amplification between HIV, HSV-2, syphilis, and HPV and implications for co-treatment strategies.

Sexually transmitted infections (STIs) and HIV frequently coexist and may interact through shared biological, immunological, and epidemiological pathways. This narrative review examines the biological interactions between HIV, herpes simplex virus type 2 (HSV-2), syphilis, and human papillomavirus (HPV), with particular emphasis on mucosal disruption, immune activation, and implications for integrated prevention and care. Evidence indicates that HSV-2-associated genital ulceration and recruitment of HIV-susceptible immune cells may increase HIV acquisition risk, while syphilis-associated systemic immune activation can transiently affect HIV viral load and CD4 cell counts. Persistent HPV infection may also promote inflammatory mucosal environments relevant to HIV susceptibility and HPV-associated disease in people living with HIV. However, evidence from intervention studies demonstrates that biological associations do not necessarily translate into effective HIV prevention through treatment of individual co-infections. Collectively, the evidence supports greater integration of STI screening, treatment, HPV vaccination, cancer screening, and HIV prevention and care, while highlighting important gaps in evidence regarding the clinical effectiveness of syndemic-informed integrated interventions.