Objectives: Sexually transmitted infections are a global public health concern. We aimed to assess the burden of a diverse range of sexually transmitted infections in a high HIV burden setting in Eswatini and associated risk factors.

Methods: This cross-sectional study enrolled adults accessing routine outpatient care at six sites in Shiselweni, from July 2022 to April 2023. Laboratory investigations included antibody-based tests for HIV, Treponema pallidum , hepatitis B, hepatitis C, and herpes simplex 2 viruses. The molecular-based Xpert platform tested urine samples for Chlamydia trachomatis , Neisseria gonorrhoea, Trichomonas vaginalis, self-collected vaginal/anal swabs for Human papillomavirus, and plasma for HIV viremia. We calculated the proportion of laboratory-confirmed sexually transmitted infections among available test results and identified predictors of combined Chlamydia trachomatis /Neisseria gonorrhoea/Trichomonas vaginalis infection.

Results: Of 1396 study participants, 65.4% were women, the median age was 29 (IQR 23-36) years, and 19.6% were known HIV-positive. Overall, 68.6% had symptoms suggestive of Chlamydia trachomatis /Neisseria gonorrhoea/Trichomonas vaginalis infections. Laboratory-confirmed Chlamydia trachomatis /Neisseria gonorrhoea/Trichomonas vaginalis infection was found in 31.7% (n = 443/1396), of whom 20.8% were asymptomatic. Combined Chlamydia trachomatis /Neisseria gonorrhoea/Trichomonas vaginalis infections were common even among individuals with low risk of infection (e.g., no sexual intercourse: 20.7%) and were associated with young age, factory employment, and transactional sex. Prevalences for individual sexually transmitted infections were 16.9% (n = 236/1394) for Chlamydia trachomatis , 12.4% (n = 173/1394) for Neisseria gonorrhoea, 10.6% (n = 148/1390) for Trichomonas vaginalis, and 9.7% (n = 135) for Treponema pallidum . Viral infections were high for herpes simplex 2 viruses (n = 792/1279, 61.9%) and human papillomavirus (n = 166/324, 51.2%) and lower for hepatitis B virus (n = 55/1396, 3.9%) and hepatitis C virus (n = 3/1396, 0.2%). Of 1122 clients undergoing HIV testing, 4.1% (n = 46/1122) tested positive, with 21.7% (n = 10/46) being acute/early HIV infection.

Conclusions: The substantial sexually transmitted infections burden highlights the urgent need to strengthen sexually transmitted infections service integration, expand access to affordable diagnostics, and target prevention in decentralised care. These findings support the development of context-adapted strategies to improve detection, treatment, and partner services in high-burden settings.