Judd, A.Chappell, E.Turkova, A.Le Coeur, S.Noguera-Julian, A.Goetghebuer, T.Doerholt, K.Galli, L.Pajkrt, D.Marques, L.Collins, I.Gibb, D.González-Tome, M.Navarro, M.Warszawski, J.Königs, C.Spoulou, V.Prata, F.Chiappini, E.Naver, L.Giaquinto, C.Thorne, C.Marczynska, M.Okhonskaia, L.Posfay-Barbe, K.Ounchanum, P.Techakunakorn, P.Kiseleva, G.Malyuta, R.Volokha, A.Ene, L.Goodall, R.2020-02-042020-02-042018-01-30European Pregnancy and Paediatric HIV Cohort Collaboration (EPPICC) study group in EuroCoord, Judd A, Chappell E, et al. Long-term trends in mortality and AIDS-defining events after combination ART initiation among children and adolescents with perinatal HIV infection in 17 middle- and high-income countries in Europe and Thailand: A cohort study. PLoS Med. 2018;15(1):e1002491. Published 2018 Jan 301549-1277http://hdl.handle.net/10400.16/2312Background: Published estimates of mortality and progression to AIDS as children with HIV approach adulthood are limited. We describe rates and risk factors for death and AIDS-defining events in children and adolescents after initiation of combination antiretroviral therapy (cART) in 17 middle- and high-income countries, including some in Western and Central Europe (W&CE), Eastern Europe (Russia and Ukraine), and Thailand. Methods and findings: Children with perinatal HIV aged <18 years initiating cART were followed until their 21st birthday, transfer to adult care, death, loss to follow-up, or last visit up until 31 December 2013. Rates of death and first AIDS-defining events were calculated. Baseline and time-updated risk factors for early/late (≤/>6 months of cART) death and progression to AIDS were assessed. Of 3,526 children included, 32% were from the United Kingdom or Ireland, 30% from elsewhere in W&CE, 18% from Russia or Ukraine, and 20% from Thailand. At cART initiation, median age was 5.2 (IQR 1.4-9.3) years; 35% of children aged <5 years had a CD4 lymphocyte percentage <15% in 1997-2003, which fell to 15% of children in 2011 onwards (p < 0.001). Similarly, 53% and 18% of children ≥5 years had a CD4 count <200 cells/mm3 in 1997-2003 and in 2011 onwards, respectively (p < 0.001). Median follow-up was 5.6 (2.9-8.7) years. Of 94 deaths and 237 first AIDS-defining events, 43 (46%) and 100 (42%) were within 6 months of initiating cART, respectively. Multivariable predictors of early death were: being in the first year of life; residence in Russia, Ukraine, or Thailand; AIDS at cART start; initiating cART on a nonnucleoside reverse transcriptase inhibitor (NNRTI)-based regimen; severe immune suppression; and low BMI-for-age z-score. Current severe immune suppression, low current BMI-for-age z-score, and current viral load >400 c/mL predicted late death. Predictors of early and late progression to AIDS were similar. Study limitations include incomplete recording of US Centers for Disease Control (CDC) disease stage B events and serious adverse events in some countries; events that were distributed over a long time period, and that we lacked power to analyse trends in patterns and causes of death over time. Conclusions: In our study, 3,526 children and adolescents with perinatal HIV infection initiated antiretroviral therapy (ART) in countries in Europe and Thailand. We observed that over 40% of deaths occurred ≤6 months after cART initiation. Greater early mortality risk in infants, as compared to older children, and in Russia, Ukraine, or Thailand as compared to W&CE, raises concern. Current severe immune suppression, being underweight, and unsuppressed viral load were associated with a higher risk of death at >6 months after initiation of cART.engAcquired Immunodeficiency SyndromeAdolescentAnti-Retroviral AgentsChildChild, PreschoolCohort StudiesDrug Therapy, CombinationEuropeHIV InfectionsHumansInfantInfant, NewbornRisk FactorsThailandDisease Progressionjournal article10.1371/journal.pmed.10024911549-1676