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HIV-negative individuals with in utero HIV exposure represent an emerging population, exceeding 18 million people worldwide. Long-term clinical outcomes among HIV-exposed uninfected (HEU) individuals into adolescence and young adulthood remain unknown.U.S. academic health system.In this observational cohort study, we leveraged a patient data registry to identify 50 HEU adolescents and young adults. We also identified 141 HIV-unexposed controls that were matched to HEU subjects up to 3:1 on age of last encounter (±2 years), birthdate (±5 years), sex, race/ethnicity, and zip code. All subjects were born since 1/1/1990 with medical records available into adolescence and young adulthood. Primary outcomes were most recent BMI z-score and presence of reactive airway disease (RAD). Records were manually reviewed to extract health information.50 HEU adolescents and young adults (18±3 years, 54% men) and 141 matched controls (19±3 years, 54% men) were compared. HEU individuals had a higher BMI z-score (1.12±1.08 vs. 0.73±1.09, P=0.03) as well as an increased prevalence of obesity (42% vs. 22%, P=0.009) compared to controls. HEU subjects also had a higher prevalence of RAD versus controls (40% vs. 23%, P=0.03). These differences persisted upon adjusting for demographic, socioeconomic, maternal, and birth-related factors. Maternal prenatal CD4+ T cell count was inversely associated with BMI z-score among HEU adolescents (r=-0.47, P=0.01).HEU adolescents and young adults exhibited a heightened prevalence of obesity and RAD compared to HIV-unexposed controls. Additional studies are needed to optimize care for the expanding population of HEU individuals transitioning to adulthood.