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The ongoing spread of human immunodeficiency virus (HIV) has driven novel interventions, such as antiretrovirals, for pre-exposure prophylaxis. Interventions have overlooked a high-risk Sub-Saharan African population: adolescent girls and young women (AGYW), particularly those under 18. We apply the Balkus risk tool among rural South African AGYW (n = 971) in a hyper-endemic setting, identify limitations, and assess deficiencies with modern statistical techniques. We apply the “Ayton” tool, the first risk tool applicable to sub-Saharan African AGYW, and compare performance of Balkus and Ayton tools under varying conditions. The Ayton tool more effectively predicted HIV acquisition. In low and high-risk AGYW, the Ayton tool out-performed the Balkus tool, which did not distinguish between risk classes. The Ayton tool better captured HIV acquisition risk and risk heterogeneities due to its AGYW-focused design. Findings support use of the Ayton tool for AGYW and underscore the need for diverse prognostic tools considering epidemic severity, age, sex and transmission.   Clinical Trial Number  ClinicalTrials.gov (NCT01187979) and the South African National Clinical Trials Registry (SANCTR) (DOH-27-0812-3345).

Identification of adolescent girls and young women for targeted HIV prevention: a new risk scoring tool in KwaZulu Natal, South Africa