TY  - JOUR
A1  - Judd, Ali
A1  - Chappell, Elizabeth
A1  - Turkova, Anna
A1  - Le Coeur, Sophie
A1  - Noguera-Julian, Antoni
A1  - Goetghebuer, Tessa
A1  - Doerholt, Katja
A1  - Galli, Luisa
A1  - Pajkrt, Dasja
A1  - Marques, Laura
A1  - Collins, Intira Jeannie
A1  - Gibb, Diana M.
A1  - González Tomé, María Isabel
A1  - Navarro, Marisa
A1  - Warszawski, Josiane
A1  - Königs, Christoph
A1  - Spoulou, Vana
A1  - Prata, Filipa
A1  - Chiappini, Elena
A1  - Naver, Lars
A1  - Giaquinto, Carlo
A1  - Thorne, Claire
A1  - Marczynska, Magdalena
A1  - Okhonskaia, Liubov
A1  - Posfay-Barbe, Klara M.
A1  - Ounchanum, Pradthana
A1  - Techakunakorn, Pornchai
A1  - Kiseleva, Galina
A1  - Malyuta, Ruslan
A1  - Volokha, Alla
A1  - Ene, Luminita
A1  - Goodall, Ruth
T1  - 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
T2  - PLoS medicine
N2  - Background: 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.
KW  - Death rates
KW  - AIDS
KW  - HIV
KW  - Antiretroviral therapy
KW  - Europe
KW  - Immune suppression
KW  - Children
KW  - Viral load
Y1  - 2018
UR  - http://publikationen.ub.uni-frankfurt.de/frontdoor/index/index/docId/45623
UR  - https://nbn-resolving.org/urn:nbn:de:hebis:30:3-456236
SN  - 1549-1676
SN  - 1549-1277
N1  - Copyright: © 2018 The European Pregnancy and Paediatric HIV Cohort Collaboration (EPPICC) study group in EuroCoord et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
VL  - 15
IS  - (1): e1002491
SP  - 1
EP  - 19
PB  - PLoS
CY  - Lawrence, Kan.
ER  -