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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

2018-01-30Journal article Open access
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dc.contributor.authorJudd, A.
dc.contributor.authorChappell, E.
dc.contributor.authorTurkova, A.
dc.contributor.authorLe Coeur, S.
dc.contributor.authorNoguera-Julian, A.
dc.contributor.authorGoetghebuer, T.
dc.contributor.authorDoerholt, K.
dc.contributor.authorGalli, L.
dc.contributor.authorPajkrt, D.
dc.contributor.authorMarques, L.
dc.contributor.authorCollins, I.
dc.contributor.authorGibb, D.
dc.contributor.authorGonzález-Tome, M.
dc.contributor.authorNavarro, M.
dc.contributor.authorWarszawski, J.
dc.contributor.authorKönigs, C.
dc.contributor.authorSpoulou, V.
dc.contributor.authorPrata, F.
dc.contributor.authorChiappini, E.
dc.contributor.authorNaver, L.
dc.contributor.authorGiaquinto, C.
dc.contributor.authorThorne, C.
dc.contributor.authorMarczynska, M.
dc.contributor.authorOkhonskaia, L.
dc.contributor.authorPosfay-Barbe, K.
dc.contributor.authorOunchanum, P.
dc.contributor.authorTechakunakorn, P.
dc.contributor.authorKiseleva, G.
dc.contributor.authorMalyuta, R.
dc.contributor.authorVolokha, A.
dc.contributor.authorEne, L.
dc.contributor.authorGoodall, R.
dc.date.accessioned2020-02-04T11:25:35Z
dc.date.available2020-02-04T11:25:35Z
dc.date.issued2018-01-30
dc.description.abstractBackground: 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.pt_PT
dc.description.versioninfo:eu-repo/semantics/publishedVersionpt_PT
dc.identifier.citationEuropean 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 30pt_PT
dc.identifier.doi10.1371/journal.pmed.1002491pt_PT
dc.identifier.eissn1549-1676
dc.identifier.issn1549-1277
dc.identifier.urihttp://hdl.handle.net/10400.16/2312
dc.language.isoengpt_PT
dc.peerreviewedyespt_PT
dc.publisherPublic Library of Sciencept_PT
dc.relation.publisherversionhttps://journals.plos.org/plosmedicine/article?id=10.1371/journal.pmed.1002491pt_PT
dc.subjectAcquired Immunodeficiency Syndromept_PT
dc.subjectAdolescentpt_PT
dc.subjectAnti-Retroviral Agentspt_PT
dc.subjectChildpt_PT
dc.subjectChild, Preschoolpt_PT
dc.subjectCohort Studiespt_PT
dc.subjectDrug Therapy, Combinationpt_PT
dc.subjectEuropept_PT
dc.subjectHIV Infectionspt_PT
dc.subjectHumanspt_PT
dc.subjectInfantpt_PT
dc.subjectInfant, Newbornpt_PT
dc.subjectRisk Factorspt_PT
dc.subjectThailandpt_PT
dc.subjectDisease Progressionpt_PT
dc.titleLong-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 studypt_PT
dc.typejournal article
dspace.entity.typePublication
oaire.citation.conferencePlaceUnited States of Americapt_PT
oaire.citation.issue1pt_PT
oaire.citation.startPagee1002491pt_PT
oaire.citation.titlePLoS medicinept_PT
oaire.citation.volume15pt_PT
rcaap.rightsopenAccesspt_PT
rcaap.typearticlept_PT

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