Objective: Sexually transmitted infections (STIs), including syphilis, chlamydia, gonorrhoea and trichomoniasis, are of global public health concern. While STI incidence rates in sub-Saharan Africa are high, longitudinal data on incidence and recurrence of STIs are scarce, particularly in rural areas. We determined the incidence rates of curable STIs in HIV-negative women during 96 weeks in a rural South African setting. Methods: We prospectively followed participants enrolled in a randomised controlled trial to evaluate the safety and efficacy of a dapivirine-containing vaginal ring for HIV prevention in Limpopo province, South Africa. Participants were included if they were female, aged 18–45, sexually active, not pregnant and HIV-negative. Twelve-weekly laboratory STI testing was performed during 96 weeks of follow-up. Treatment was provided based on vaginal discharge by physical examination or after a laboratory-confirmed STI. Results: A total of 119 women were included in the study. Prevalence of one or more STIs at baseline was 35.3%. Over 182 person-years at risk (PYAR), a total of 149 incident STIs were diagnosed in 75 (65.2%) women with incidence rates of 45.6 events/PYAR for chlamydia, 27.4 events/100 PYAR for gonorrhoea and 8.2 events/100 PYAR for trichomoniasis. Forty-four women developed ≥2 incident STIs. Risk factors for incident STI were in a relationship ≤3 years (adjusted hazard ratio [aHR]: 1.86; 95% confidece interval [CI]: 1.04–2.65) and having an STI at baseline (aHR: 1.66; 95% CI: 1.17–2.96). Sensitivity and specificity of vaginal discharge for laboratory-confirmed STI were 23.6% and 87.7%, respectively. Conclusion: This study demonstrates high STI incidence in HIV-negative women in rural South Africa. Sensitivity of vaginal discharge was poor and STI recurrence rates were high, highlighting the shortcomings of syndromic management in the face of asymptomatic STIs in this setting
