Objective: Most data published on adolescents living with HIV (ALH) have been collected before the large diffusion of second-generation integrase strand transfer inhibitors (INSTI) among the pediatric population. We analyzed the nationwide ANRS-MIE CO10 Pediatric cohort to assess the changes over time in health and social outcomes of French ALH. Design: The cohort enrolled children born in France since 1985 and, from 2005, children diagnosed with HIV at ≤13 years, including those born abroad if antiretroviral-naive at first medical care in France. Methods: Adolescents aged ≥10 years at their last visit were included in this analysis. Their characteristics were compared between three periods of birth (1985-1993, 1994-1999, 2000-2010). Results: Overall, 529 ALH were included. Their median age at first HAART initiation decreased from 94 to 29 months (p < 0·0001). At the last evaluation, the proportions of ALH receiving HAART, receiving INSTI, having HIV-RNA < 50 copies/mL and having CD4 count ≥500/μL increased over time (p < 0.0001), reaching 98·7%, 53·3%, 81·3% and 85·0%, respectively, for those born in 2000-2010. The proportion of maternal and paternal orphans decreased until 14·4% and 11·0%, respectively, for ALH born recently. Compared to middle adolescents (15-17 years) born in 1994-1999, those born in 2000-2010 demonstrated higher academic success (69·2% versus 42·3%) and less frequent academic failure (4·6% versus 6·2%). Conclusions: Despite spectacular improvement in their health and immunovirological status, ALH remain vulnerable compared to other French adolescents, with a higher risk of being orphan and/or experiencing academic failure. Specific interventions are required to improve their global quality of life. Copyright © 2025 Wolters Kluwer Health, Inc.< Leer menos