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
Abstract 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 associatio...
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2016-11-01
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Online Access: | http://link.springer.com/article/10.1186/s12879-016-1968-2 |
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record_format |
Article |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Nicole Ngo-Giang-Huong Linda Wittkop Ali Judd Peter Reiss Tessa Goetghebuer Dan Duiculescu Antoni Noguera-Julian Magdalena Marczynska Carlo Giacquinto Luminita Ene Jose T. Ramos Cristina Cellerai Thomas Klimkait Benedicte Brichard Niels Valerius Caroline Sabin Ramon Teira Niels Obel Christoph Stephan Stéphane de Wit Claire Thorne Diana Gibb Christine Schwimmer Maria Athena Campbell Deenan Pillay Marc Lallemant The EuroCoord-CHAIN-EPPICC joint project study group |
spellingShingle |
Nicole Ngo-Giang-Huong Linda Wittkop Ali Judd Peter Reiss Tessa Goetghebuer Dan Duiculescu Antoni Noguera-Julian Magdalena Marczynska Carlo Giacquinto Luminita Ene Jose T. Ramos Cristina Cellerai Thomas Klimkait Benedicte Brichard Niels Valerius Caroline Sabin Ramon Teira Niels Obel Christoph Stephan Stéphane de Wit Claire Thorne Diana Gibb Christine Schwimmer Maria Athena Campbell Deenan Pillay Marc Lallemant The EuroCoord-CHAIN-EPPICC joint project study group 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 BMC Infectious Diseases HIV Children Pre-treatment drug resistance mutations Virological failure First-line combination antiretroviral therapy |
author_facet |
Nicole Ngo-Giang-Huong Linda Wittkop Ali Judd Peter Reiss Tessa Goetghebuer Dan Duiculescu Antoni Noguera-Julian Magdalena Marczynska Carlo Giacquinto Luminita Ene Jose T. Ramos Cristina Cellerai Thomas Klimkait Benedicte Brichard Niels Valerius Caroline Sabin Ramon Teira Niels Obel Christoph Stephan Stéphane de Wit Claire Thorne Diana Gibb Christine Schwimmer Maria Athena Campbell Deenan Pillay Marc Lallemant The EuroCoord-CHAIN-EPPICC joint project study group |
author_sort |
Nicole Ngo-Giang-Huong |
title |
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 |
title_short |
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 |
title_full |
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 |
title_fullStr |
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 |
title_full_unstemmed |
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 |
title_sort |
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 |
publisher |
BMC |
series |
BMC Infectious Diseases |
issn |
1471-2334 |
publishDate |
2016-11-01 |
description |
Abstract 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. |
topic |
HIV Children Pre-treatment drug resistance mutations Virological failure First-line combination antiretroviral therapy |
url |
http://link.springer.com/article/10.1186/s12879-016-1968-2 |
work_keys_str_mv |
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doaj-efa9b6d7a2c24b41a765d7da1667fb802020-11-25T03:13:34ZengBMCBMC Infectious Diseases1471-23342016-11-0116111010.1186/s12879-016-1968-2Prevalence and effect of pre-treatment drug resistance on the virological response to antiretroviral treatment initiated in HIV-infected children – a EuroCoord-CHAIN-EPPICC joint projectNicole Ngo-Giang-Huong0Linda Wittkop1Ali Judd2Peter Reiss3Tessa Goetghebuer4Dan Duiculescu5Antoni Noguera-Julian6Magdalena Marczynska7Carlo Giacquinto8Luminita Ene9Jose T. Ramos10Cristina Cellerai11Thomas Klimkait12Benedicte Brichard13Niels Valerius14Caroline Sabin15Ramon Teira16Niels Obel17Christoph Stephan18Stéphane de Wit19Claire Thorne20Diana Gibb21Christine Schwimmer22Maria Athena Campbell23Deenan Pillay24Marc Lallemant25The EuroCoord-CHAIN-EPPICC joint project study groupIRD UMI 174 - PHPT-Faculty of Associated Medical Sciences, Chiang Mai UniversityUniv. Bordeaux, ISPED; INSERM, Centre INSERM U1219; CHU de Bordeaux, Pole de Sante PubliqueMedical Research Council Clinical Trials Unit, University College LondonAcademic Medical Centre, University of AmsterdamHôpital Saint-Pierre“Dr. Victor Babes” Hospital for Infectious and Tropical DiseasesSant Joan de Déu Hospital, University of BarcelonaMedical University of WarsawUniversity of Padua“Dr. Victor Babes” Hospital for Infectious and Tropical DiseasesUniversity Hospital of GetafeLausanne University HospitalUniversity of BaselSaint-LucHvidovre Hospital, University of CopenhagenUniversity College LondonHospital de SierrallanaRigshospitalet, Copenhagen University HospitalUniversity Clinic FrankfurtAIDS Reference Center, CHU Saint-PierreUniversity College London, Institute of Child HealthMedical Research Council Clinical Trials UnitBordeaux RCC, INSERM, U897Copenhagen RCC, RigshospitaletUniversity College LondonIRD UMI 174 - PHPT-Faculty of Associated Medical Sciences, Chiang Mai UniversityAbstract 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.http://link.springer.com/article/10.1186/s12879-016-1968-2HIVChildrenPre-treatment drug resistance mutationsVirological failureFirst-line combination antiretroviral therapy |