OBJECTIVE: To measure mortality incidence rates (IR) and incidence rate ratios (IRR) in adolescents and youth living with perinatally-acquired HIV (YPHIV) compared to those living with non-perinatally-acquired HIV (YNPHIV), by region, by sex, and during the ages of 10-14, 15-19, and 20-24 years in IeDEA. DESIGN AND METHODS: All those with a confirmed HIV diagnosis, antiretroviral therapy (ART)-naive at enrollment, and who have post-ART follow-up while aged 10-24 between 2004-2016 were included. We estimated post-ART mortality IRs and 95% confidence intervals (95%CI) per 100 person-years (PY) for YPHIV (enrolled into care <10 years of age) and YNPHIV (enrolled ≥ 10 years and < 25 years). We estimate mortality IRRs in a negative binomial regression model, adjusted for sex, region time-varying age, CD4 count at ART initiation (<350 cells/μL, ≥350 cells/μL, unknown), and time on ART (<12 months, ≥12 months). RESULTS: Overall, 104,846 adolescents and youth were included: 21,340 (20%) YPHIV (50% female) and 83,506 YNPHIV (80% female). Overall mortality IRs were higher among YNPHIV (IR: 2.3/100PY; 95%CI: 2.2-2.4) compared to YPHIV (IR: 0.7/100PY; 95%CI: 0.7-0.8). Among adolescents aged 10-19 years, mortality was lower among YPHIV compared to YNPHIV (all IRRs < 1, ranging from 0.26, 95%CI: 0.13-0.49 in 10-14-year-old males in the Asia-Pacific to 0.51, 95%CI: 0.30-0.87 in 15-19-year-old males in West Africa). CONCLUSION: We report substantial amount of deaths occurring during adolescence. Mortality was significantly higher among YNPHIV compared to YPHIV. Specific interventions including HIV testing and early engagement in care are urgently needed to improve survival among YNPHIV.< Leer menos