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dc.contributor.authorNicole Ngo-Giang-Huongen_US
dc.contributor.authorLinda Wittkopen_US
dc.contributor.authorAli Judden_US
dc.contributor.authorPeter Reissen_US
dc.contributor.authorTessa Goetghebueren_US
dc.contributor.authorDan Duiculescuen_US
dc.contributor.authorAntoni Noguera-Julianen_US
dc.contributor.authorMagdalena Marczynskaen_US
dc.contributor.authorCarlo Giacquintoen_US
dc.contributor.authorLuminita Eneen_US
dc.contributor.authorJose T. Ramosen_US
dc.contributor.authorCristina Celleraien_US
dc.contributor.authorThomas Klimkaiten_US
dc.contributor.authorBenedicte Bricharden_US
dc.contributor.authorNiels Valeriusen_US
dc.contributor.authorCaroline Sabinen_US
dc.contributor.authorRamon Teiraen_US
dc.contributor.authorNiels Obelen_US
dc.contributor.authorChristoph Stephanen_US
dc.contributor.authorStéphane de Witen_US
dc.contributor.authorClaire Thorneen_US
dc.contributor.authorDiana Gibben_US
dc.contributor.authorChristine Schwimmeren_US
dc.contributor.authorMaria Athena Campbellen_US
dc.contributor.authorDeenan Pillayen_US
dc.contributor.authorMarc Lallemanten_US
dc.contributor.authorVibeke Rosenfeldten_US
dc.contributor.authorFrançois Dabisen_US
dc.description.abstract© 2016 The Author(s). Background: Few studies have evaluated the impact of pre-treatment drug resistance (PDR) on response to combination antiretroviral treatment (cART) in children. The objective of this joint EuroCoord-CHAIN-EPPICC/PENTA project was to assess the prevalence of PDR mutations and their association with virological outcome in the first year of cART in children. Methods: HIV-infected children <18 years initiating cART between 1998 and 2008 were included if having at least one genotypic resistance test prior to cART initiation. We used the World Health Organization 2009 resistance mutation list and Stanford algorithm to infer resistance to prescribed drugs. Time to virological failure (VF) was defined as the first of two consecutive HIV-RNA > 500 copies/mL after 6 months cART and was assessed by Cox proportional hazards models. All models were adjusted for baseline demographic, clinical, immunology and virology characteristics and calendar period of cART start and initial cART regimen. Results: Of 476 children, 88 % were vertically infected. At cART initiation, median (interquartile range) age was 6.6 years (2.1-10.1), CD4 cell count 297 cells/mm3(98-639), and HIV-RNA 5.2 log10copies/mL (4.7-5.7). Of 37 children (7.8 %, 95 % confidence interval (CI), 5.5-10.6) harboring a virus with ≥1 PDR mutations, 30 children had a virus resistant to ≥1 of the prescribed drugs. Overall, the cumulative Kaplan-Meier estimate for virological failure was 19.8 % (95 %CI, 16.4-23.9). Cumulative risk for VF tended to be higher among children harboring a virus with PDR and resistant to ≥1 drug prescribed than among those receiving fully active cART: 32.1 % (17.2-54.8) versus 19.4 % (15.9-23.6) (P = 0.095). In multivariable analysis, age was associated with a higher risk of VF with a 12 % reduced risk per additional year (HR 0.88; 95 %CI, 0.82-0.95; P < 0.001). Conclusions: PDR was not significantly associated with a higher risk of VF in children in the first year of cART. The risk of VF decreased by 12 % per additional year at treatment initiation which may be due to fading of PDR mutations over time. Lack of appropriate formulations, in particular for the younger age group, may be an important determinant of virological failure.en_US
dc.titlePrevalence and effect of pre-treatment drug resistance on the virological response to antiretroviral treatment initiated in HIV-infected children - a EuroCoord-CHAIN-EPPICC joint projecten_US
article.title.sourcetitleBMC Infectious Diseasesen_US
article.volume16en_US Mai Universityen_US School of Public Healthen_US de Bordeauxen_US Medical Centre, University of Amsterdamen_US Hospitalier Universitaire Saint Pierre, Brusselsen_US Babes National Instituteen_US de Barcelonaen_US University of Warsawen_US degli Studi di Padovaen_US Universitario de Getafeen_US Hospitalier Universitaire Vaudoisen_US Baselen_USôpital Saint-Lucen_US Universiteten_US Sierrallanaen_US und Fachbereich Medizin Johann Wolfgang Goethe-Universitat Frankfurt am Mainen_US Institute of Child Healthen_US Research Councilen_US
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