TY - JOUR A1 - Ngo-Giang-Huong, Nicole A1 - Wittkop, Linda A1 - Judd, Ali A1 - Reiss, Peter A1 - Goetghebuer, Tessa A1 - Duiculescu, Dan A1 - Noguera-Julian, Antoni A1 - Marczynska, Magdalena A1 - Giacquinto, Carlo A1 - Ene, Luminita A1 - Ramos, Jose T. A1 - Cellerai, Cristina A1 - Klimkait, Thomas A1 - Brichard, Benedicte A1 - Valerius, Niels A1 - Sabin, Caroline A1 - Teira, Ramon A1 - Obel, Niels A1 - Stephan, Christoph A1 - Wit, Stephane de A1 - Thorne, Claire A1 - Gibb, Diana A1 - Schwimmer, Christine A1 - Campbell, Maria Athena A1 - Pillay, Deenan A1 - Lallemant, Marc T1 - Prevalence and effect of pre-treatment drug resistance on the virological response to antiretroviral treatment initiated in HIV-infected children – a EuroCoord-CHAIN-EPPICC joint project T2 - BMC infectious diseases N2 - 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. KW - HIV KW - Children KW - Pre-treatment drug resistance mutations KW - Virological failure KW - First-line combination antiretroviral therapy Y1 - 2016 UR - http://publikationen.ub.uni-frankfurt.de/frontdoor/index/index/docId/45782 UR - https://nbn-resolving.org/urn:nbn:de:hebis:30:3-457824 SN - 1471-2334 N1 - Open Access: This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated. VL - 16 IS - 1, Art. 654 SP - 1 EP - 10 PB - BioMed Central ; Springer CY - London ; Berlin ; Heidelberg ER -