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
Por:
Judd A, Chappell E, Turkova A, Le Coeur S, Noguera-Julian A, Goetghebuer T, Doerholt K, Galli L, Pajkrt D, Marques L, Collins IJ, Gibb DM, Gonzalez Tome MI, Navarro M, Warszawski J, Konigs 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 and European Pregnancy and Paediatric HIV Cohort Collaboration (EPPICC) study group
Publicada:
1 ene 2018
Ahead of Print:
30 ene 2018
Resumen:
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/mm(3) 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.
Filiaciones:
Judd A:
MRC Clinical Trials Unit, University College London (UCL), London, United Kingdom
Chappell E:
MRC Clinical Trials Unit, University College London (UCL), London, United Kingdom
Turkova A:
MRC Clinical Trials Unit, University College London (UCL), London, United Kingdom
Le Coeur S:
Institut National d'Etude Demographique (INED), Mortality, Health and Epidemiology Unit, Paris, France
Institut de Recherche pour le Developpement (IRD), UMI 174/PHPT, Chiang Mai, Thailand
Noguera-Julian A:
Unitat d'Infectologia, Servei de Pediatria, Hospital Sant Joan de Deu, Universitat de Barcelona, Barcelona, Spain
Goetghebuer T:
Hopital St Pierre, Brussels, Belgium
Doerholt K:
St George's Healthcare NHS Trust, London, United Kingdom
Galli L:
Department of Health Sciences, Pediatric Unit, University of Florence, Florence, Italy
Pajkrt D:
Department of Pediatric Infectious Diseases, Emma Children's Hospital, Academic Medical Center, Amsterdam, the Netherlands
Marques L:
Centro Hospitalar do Porto, Porto, Portugal
Collins IJ:
MRC Clinical Trials Unit, University College London (UCL), London, United Kingdom
Gibb DM:
MRC Clinical Trials Unit, University College London (UCL), London, United Kingdom
Gonzalez Tome MI:
Hospital Doce de Octubre, Madrid, Spain
Navarro M:
Hospital General Universitario "Gregorio Maranon", Madrid, Spain
Warszawski J:
Institut National de la Sante et de la Recherche (INSERM), Paris, France
Konigs C:
University Hospital Frankfurt, Department of Paediatrics, Goethe University, Frankfurt, Germany
Spoulou V:
University of Athens Medical School, Athens, Greece
Prata F:
Hospital de Santa Maria, Lisbon, Portugal
Chiappini E:
Department of Health Sciences, Pediatric Unit, University of Florence, Florence, Italy
Naver L:
Karolinska University Hospital, Stockholm, Sweden
Giaquinto C:
Paediatric European Network for the Treatment of AIDS (PENTA), Padova, Italy
Thorne C:
UCL Great Ormond Street Institute of Child Health, London, United Kingdom
Marczynska M:
Medical University of Warsaw, Hospital of Infectious Diseases, Warsaw, Poland
Okhonskaia L:
Republican Hospital of Infectious Diseases, St Petersburg, Russia
Posfay-Barbe K:
Hopitaux Universitaires de Geneve, Geneve, Switzerland
Ounchanum P:
Chiang Rai Prachanukroh Hospital, Chiang Rai, Thailand
Techakunakorn P:
Department of Pediatrics, Phayao Provincial Hospital, Phayao, Thailand
Kiseleva G:
Shupyk National Medical Academy of Postgraduate Education, Kiev, Ukraine
Malyuta R:
Perinatal Prevention of AIDS Initiative, Odessa, Ukraine
Volokha A:
Shupyk National Medical Academy of Postgraduate Education, Kiev, Ukraine
Ene L:
Victor Babes Hospital, Bucharest, Romania
Goodall R:
MRC Clinical Trials Unit, University College London (UCL), London, United Kingdom
Green Accepted, Green Submitted, Green Published, gold
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