Risk of triple-class virological failure in children with HIV: a retrospective cohort study

Ali Judd; Hannah Castro; Diana M. Gibb; Karina Butler; Rebecca K. Lodwick; Ard van Sighem; Jose T. Ramos; Josiane Warsawski; Claire Thorne; Antoni Noguera-Julian; Niels Obel; Dominique Costagliola; Pat A. Tookey; Céline Colin; Jesper Kjaer; Jesper Grarup; Genevieve Chene; Andrew Phillips; Andrea Antinori; Antonella Castagna; Alessandro Cozzi-Lepri; Andrea De Luca; Stephane De Wit; Maria Dorrucci; Xavier Duval; Federico García; Jade Ghosn; Huldrych Günthard; Bruno Ledergerber; Sergio Lo Caputo; Bernard Masquelier; Laurence Meyer; Amanda Mocroft; Cristina Mussini; Dimitrios Paraskevis; Roger Paredes; Santiago Pérez-Hoyos; Deenan Pillay; Daniel Podzamczer; Peter Reiss; Christoph Stephan; Ramón Teira; Carlo Torti; Giota Touloumi; Robert Zangerle; Josiane Warszawski; François Dabis; Murielle Mary Krause; Catherine Leport; Frank de Wolf; Maria Prins; Heiner C. Bücher; Caroline Sabin; Gerd Fätkenheuer; Julia Del Amo; Ole Kirk; Antonella D.Arminio Monforte; Pier Angelo Tovo; Maurizio de Martino; Norbert H. Brockmeyer; Manuel Battegay; Patrick Francioli; Dolors Carnicer-Pont; Jordi Casabona; Jose M. Miró; Tessa Goetghebuer; Myriam Garrido; Nikos Dedes; Ian Weller; Fideline Collin-Filleul; Christine Schwimmer; Michelle Ellefson; Maria Paulsen; Julia Bohlius; Vincent Bouteloup; Matthias Egger; Hansjakob Furrer; Olivier Lambotte; Charlotte Lewden; Sophie Matheron; Massimo Puoti; Joanne Reekie; Colette Smit; Jonathan Sterne; Rodolphe Thiebaut; Linda Wittkop

doi:10.1016/S0140-6736(11)60208-0

Risk of triple-class virological failure in children with HIV: a retrospective cohort study

Ali Judd, Hannah Castro, Diana M. Gibb, Karina Butler, Rebecca K. Lodwick, Ard van Sighem, Jose T. Ramos, Josiane Warsawski, Claire Thorne, Antoni Noguera-Julian, Niels Obel, Dominique Costagliola, Pat A. Tookey, Céline Colin, Jesper Kjaer, Jesper Grarup, Genevieve Chene, Andrew Phillips, Andrea Antinori, Antonella CastagnaAlessandro Cozzi-Lepri, Andrea De Luca, Stephane De Wit, Maria Dorrucci, Xavier Duval, Federico García, Jade Ghosn, Huldrych Günthard, Bruno Ledergerber, Sergio Lo Caputo, Bernard Masquelier, Laurence Meyer, Amanda Mocroft, Cristina Mussini, Dimitrios Paraskevis, Roger Paredes, Santiago Pérez-Hoyos, Deenan Pillay, Daniel Podzamczer, Peter Reiss, Christoph Stephan, Ramón Teira, Carlo Torti, Giota Touloumi, Robert Zangerle, Josiane Warszawski, François Dabis, Murielle Mary Krause, Catherine Leport, Frank de Wolf, Maria Prins, Heiner C. Bücher, Caroline Sabin, Gerd Fätkenheuer, Julia Del Amo, Ole Kirk, Antonella D.Arminio Monforte, Pier Angelo Tovo, Maurizio de Martino, Norbert H. Brockmeyer, Manuel Battegay, Patrick Francioli, Dolors Carnicer-Pont, Jordi Casabona, Jose M. Miró, Tessa Goetghebuer, Myriam Garrido, Nikos Dedes, Ian Weller, Fideline Collin-Filleul, Christine Schwimmer, Michelle Ellefson, Maria Paulsen, Julia Bohlius, Vincent Bouteloup, Matthias Egger, Hansjakob Furrer, Olivier Lambotte, Charlotte Lewden, Sophie Matheron, Massimo Puoti, Joanne Reekie, Colette Smit, Jonathan Sterne, Rodolphe Thiebaut, Linda Wittkop

School of Civil Engineering & Surveying

Research output: Contribution to journal › Article › peer-review

Abstract

Background: In adults with HIV treated with antiretroviral drug regimens from within the three original drug classes (nucleoside or nucleotide reverse transcriptase inhibitors [NRTIs], non-NRTIs [NNRTIs], and protease inhibitors), virological failure occurs slowly, suggesting that long-term virological suppression can be achieved in most people, even in areas where access is restricted to drugs from these classes. It is unclear whether this is the case for children, the group who will need to maintain viral suppression for longest. We aimed to determine the rate and predictors of triple-class virological failure to the three original drugs classes in children.

Methods: In the Collaboration of Observational HIV Epidemiological Research Europe, the rate of triple-class virological failure was studied in children infected perinatally with HIV who were aged less than 16 years, starting antiretroviral therapy (ART) with three or more drugs, between 1998 and 2008. We used Kaplan-Meier and Cox regression methods to investigate the risk and predictors of triple-class virological failure after ART initiation.

Findings: Of 1007 children followed up for a median of 4.2 (IQR 2.4-6.5) years, 237 (24%) were triple-class exposed and 105 (10%) had triple-class virological failure, of whom 29 never had a viral-load measurement less than 500 copies per mL. Incidence of triple-class virological failure after ART initiation increased with time, and risk by 5 years after ART initiation was 12.0% (95% CI 9.4-14.6). In multivariate analysis, older age at ART initiation was associated with increased risk of failure (p=0.02). Of 686 children starting ART with NRTIs and either a NNRTI or ritonavir-boosted protease inhibitor, the rate of failure was higher than in adults with heterosexually transmitted HIV (hazard ratio 2.2 [95% CI 1.6-3.0, p<0.0001]).

Interpretation: Findings highlight the challenges of attaining long-term viral suppression in children who will be taking life-long ART. Early identification of children not responding to ART, adherence support, particularly for children and adolescents aged 13 years or older starting ART, and ART simplification strategies are all needed to attain and sustain virological suppression.

Original language	English
Pages (from-to)	1580-1587
Number of pages	8
Journal	The Lancet
Volume	377
Issue number	9777
Early online date	20 Apr 2011
DOIs	https://doi.org/10.1016/S0140-6736(11)60208-0
Publication status	Published - 7 May 2011

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This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1016/S0140-6736(11)60208-0

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Judd, A., Castro, H., Gibb, D. M., Butler, K., Lodwick, R. K., van Sighem, A., Ramos, J. T., Warsawski, J., Thorne, C., Noguera-Julian, A., Obel, N., Costagliola, D., Tookey, P. A., Colin, C., Kjaer, J., Grarup, J., Chene, G., Phillips, A., Antinori, A., ... Wittkop, L. (2011). Risk of triple-class virological failure in children with HIV: a retrospective cohort study. The Lancet, 377(9777), 1580-1587. https://doi.org/10.1016/S0140-6736(11)60208-0

@article{58ba9924f86e42f894ba689942643ba0,

title = "Risk of triple-class virological failure in children with HIV: a retrospective cohort study",

abstract = "Background: In adults with HIV treated with antiretroviral drug regimens from within the three original drug classes (nucleoside or nucleotide reverse transcriptase inhibitors [NRTIs], non-NRTIs [NNRTIs], and protease inhibitors), virological failure occurs slowly, suggesting that long-term virological suppression can be achieved in most people, even in areas where access is restricted to drugs from these classes. It is unclear whether this is the case for children, the group who will need to maintain viral suppression for longest. We aimed to determine the rate and predictors of triple-class virological failure to the three original drugs classes in children. Methods: In the Collaboration of Observational HIV Epidemiological Research Europe, the rate of triple-class virological failure was studied in children infected perinatally with HIV who were aged less than 16 years, starting antiretroviral therapy (ART) with three or more drugs, between 1998 and 2008. We used Kaplan-Meier and Cox regression methods to investigate the risk and predictors of triple-class virological failure after ART initiation. Findings: Of 1007 children followed up for a median of 4.2 (IQR 2.4-6.5) years, 237 (24%) were triple-class exposed and 105 (10%) had triple-class virological failure, of whom 29 never had a viral-load measurement less than 500 copies per mL. Incidence of triple-class virological failure after ART initiation increased with time, and risk by 5 years after ART initiation was 12.0% (95% CI 9.4-14.6). In multivariate analysis, older age at ART initiation was associated with increased risk of failure (p=0.02). Of 686 children starting ART with NRTIs and either a NNRTI or ritonavir-boosted protease inhibitor, the rate of failure was higher than in adults with heterosexually transmitted HIV (hazard ratio 2.2 [95% CI 1.6-3.0, p<0.0001]). Interpretation: Findings highlight the challenges of attaining long-term viral suppression in children who will be taking life-long ART. Early identification of children not responding to ART, adherence support, particularly for children and adolescents aged 13 years or older starting ART, and ART simplification strategies are all needed to attain and sustain virological suppression.",

author = "Ali Judd and Hannah Castro and Gibb, {Diana M.} and Karina Butler and Lodwick, {Rebecca K.} and {van Sighem}, Ard and Ramos, {Jose T.} and Josiane Warsawski and Claire Thorne and Antoni Noguera-Julian and Niels Obel and Dominique Costagliola and Tookey, {Pat A.} and C{\'e}line Colin and Jesper Kjaer and Jesper Grarup and Genevieve Chene and Andrew Phillips and Andrea Antinori and Antonella Castagna and Alessandro Cozzi-Lepri and {De Luca}, Andrea and {De Wit}, Stephane and Maria Dorrucci and Xavier Duval and Federico Garc{\'i}a and Jade Ghosn and Huldrych G{\"u}nthard and Bruno Ledergerber and Caputo, {Sergio Lo} and Bernard Masquelier and Laurence Meyer and Amanda Mocroft and Cristina Mussini and Dimitrios Paraskevis and Roger Paredes and Santiago P{\'e}rez-Hoyos and Deenan Pillay and Daniel Podzamczer and Peter Reiss and Christoph Stephan and Ram{\'o}n Teira and Carlo Torti and Giota Touloumi and Robert Zangerle and Josiane Warszawski and Fran{\c c}ois Dabis and Krause, {Murielle Mary} and Catherine Leport and {de Wolf}, Frank and Maria Prins and B{\"u}cher, {Heiner C.} and Caroline Sabin and Gerd F{\"a}tkenheuer and {Del Amo}, Julia and Ole Kirk and Monforte, {Antonella D.Arminio} and Tovo, {Pier Angelo} and {de Martino}, Maurizio and Brockmeyer, {Norbert H.} and Manuel Battegay and Patrick Francioli and Dolors Carnicer-Pont and Jordi Casabona and Mir{\'o}, {Jose M.} and Tessa Goetghebuer and Myriam Garrido and Nikos Dedes and Ian Weller and Fideline Collin-Filleul and Christine Schwimmer and Michelle Ellefson and Maria Paulsen and Julia Bohlius and Vincent Bouteloup and Matthias Egger and Hansjakob Furrer and Olivier Lambotte and Charlotte Lewden and Sophie Matheron and Massimo Puoti and Joanne Reekie and Colette Smit and Jonathan Sterne and Rodolphe Thiebaut and Linda Wittkop",

year = "2011",

month = may,

day = "7",

doi = "10.1016/S0140-6736(11)60208-0",

language = "English",

volume = "377",

pages = "1580--1587",

journal = "The Lancet",

issn = "0140-6736",

publisher = "Elsevier Limited",

number = "9777",

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Judd, A, Castro, H, Gibb, DM, Butler, K, Lodwick, RK, van Sighem, A, Ramos, JT, Warsawski, J, Thorne, C, Noguera-Julian, A, Obel, N, Costagliola, D, Tookey, PA, Colin, C, Kjaer, J, Grarup, J, Chene, G, Phillips, A, Antinori, A, Castagna, A, Cozzi-Lepri, A, De Luca, A, De Wit, S, Dorrucci, M, Duval, X, García, F, Ghosn, J, Günthard, H, Ledergerber, B, Caputo, SL, Masquelier, B, Meyer, L, Mocroft, A, Mussini, C, Paraskevis, D, Paredes, R, Pérez-Hoyos, S, Pillay, D, Podzamczer, D, Reiss, P, Stephan, C, Teira, R, Torti, C, Touloumi, G, Zangerle, R, Warszawski, J, Dabis, F, Krause, MM, Leport, C, de Wolf, F, Prins, M, Bücher, HC, Sabin, C, Fätkenheuer, G, Del Amo, J, Kirk, O, Monforte, ADA, Tovo, PA, de Martino, M, Brockmeyer, NH, Battegay, M, Francioli, P, Carnicer-Pont, D, Casabona, J, Miró, JM, Goetghebuer, T, Garrido, M, Dedes, N, Weller, I, Collin-Filleul, F, Schwimmer, C, Ellefson, M, Paulsen, M, Bohlius, J, Bouteloup, V, Egger, M, Furrer, H, Lambotte, O, Lewden, C, Matheron, S, Puoti, M, Reekie, J, Smit, C, Sterne, J, Thiebaut, R & Wittkop, L 2011, 'Risk of triple-class virological failure in children with HIV: a retrospective cohort study', The Lancet, vol. 377, no. 9777, pp. 1580-1587. https://doi.org/10.1016/S0140-6736(11)60208-0

TY - JOUR

T1 - Risk of triple-class virological failure in children with HIV

T2 - a retrospective cohort study

AU - Judd, Ali

AU - Castro, Hannah

AU - Gibb, Diana M.

AU - Butler, Karina

AU - Lodwick, Rebecca K.

AU - van Sighem, Ard

AU - Ramos, Jose T.

AU - Warsawski, Josiane

AU - Thorne, Claire

AU - Noguera-Julian, Antoni

AU - Obel, Niels

AU - Costagliola, Dominique

AU - Tookey, Pat A.

AU - Colin, Céline

AU - Kjaer, Jesper

AU - Grarup, Jesper

AU - Chene, Genevieve

AU - Phillips, Andrew

AU - Antinori, Andrea

AU - Castagna, Antonella

AU - Cozzi-Lepri, Alessandro

AU - De Luca, Andrea

AU - De Wit, Stephane

AU - Dorrucci, Maria

AU - Duval, Xavier

AU - García, Federico

AU - Ghosn, Jade

AU - Günthard, Huldrych

AU - Ledergerber, Bruno

AU - Caputo, Sergio Lo

AU - Masquelier, Bernard

AU - Meyer, Laurence

AU - Mocroft, Amanda

AU - Mussini, Cristina

AU - Paraskevis, Dimitrios

AU - Paredes, Roger

AU - Pérez-Hoyos, Santiago

AU - Pillay, Deenan

AU - Podzamczer, Daniel

AU - Reiss, Peter

AU - Stephan, Christoph

AU - Teira, Ramón

AU - Torti, Carlo

AU - Touloumi, Giota

AU - Zangerle, Robert

AU - Warszawski, Josiane

AU - Dabis, François

AU - Krause, Murielle Mary

AU - Leport, Catherine

AU - de Wolf, Frank

AU - Prins, Maria

AU - Bücher, Heiner C.

AU - Sabin, Caroline

AU - Fätkenheuer, Gerd

AU - Del Amo, Julia

AU - Kirk, Ole

AU - Monforte, Antonella D.Arminio

AU - Tovo, Pier Angelo

AU - de Martino, Maurizio

AU - Brockmeyer, Norbert H.

AU - Battegay, Manuel

AU - Francioli, Patrick

AU - Carnicer-Pont, Dolors

AU - Casabona, Jordi

AU - Miró, Jose M.

AU - Goetghebuer, Tessa

AU - Garrido, Myriam

AU - Dedes, Nikos

AU - Weller, Ian

AU - Collin-Filleul, Fideline

AU - Schwimmer, Christine

AU - Ellefson, Michelle

AU - Paulsen, Maria

AU - Bohlius, Julia

AU - Bouteloup, Vincent

AU - Egger, Matthias

AU - Furrer, Hansjakob

AU - Lambotte, Olivier

AU - Lewden, Charlotte

AU - Matheron, Sophie

AU - Puoti, Massimo

AU - Reekie, Joanne

AU - Smit, Colette

AU - Sterne, Jonathan

AU - Thiebaut, Rodolphe

AU - Wittkop, Linda

PY - 2011/5/7

Y1 - 2011/5/7

N2 - Background: In adults with HIV treated with antiretroviral drug regimens from within the three original drug classes (nucleoside or nucleotide reverse transcriptase inhibitors [NRTIs], non-NRTIs [NNRTIs], and protease inhibitors), virological failure occurs slowly, suggesting that long-term virological suppression can be achieved in most people, even in areas where access is restricted to drugs from these classes. It is unclear whether this is the case for children, the group who will need to maintain viral suppression for longest. We aimed to determine the rate and predictors of triple-class virological failure to the three original drugs classes in children. Methods: In the Collaboration of Observational HIV Epidemiological Research Europe, the rate of triple-class virological failure was studied in children infected perinatally with HIV who were aged less than 16 years, starting antiretroviral therapy (ART) with three or more drugs, between 1998 and 2008. We used Kaplan-Meier and Cox regression methods to investigate the risk and predictors of triple-class virological failure after ART initiation. Findings: Of 1007 children followed up for a median of 4.2 (IQR 2.4-6.5) years, 237 (24%) were triple-class exposed and 105 (10%) had triple-class virological failure, of whom 29 never had a viral-load measurement less than 500 copies per mL. Incidence of triple-class virological failure after ART initiation increased with time, and risk by 5 years after ART initiation was 12.0% (95% CI 9.4-14.6). In multivariate analysis, older age at ART initiation was associated with increased risk of failure (p=0.02). Of 686 children starting ART with NRTIs and either a NNRTI or ritonavir-boosted protease inhibitor, the rate of failure was higher than in adults with heterosexually transmitted HIV (hazard ratio 2.2 [95% CI 1.6-3.0, p<0.0001]). Interpretation: Findings highlight the challenges of attaining long-term viral suppression in children who will be taking life-long ART. Early identification of children not responding to ART, adherence support, particularly for children and adolescents aged 13 years or older starting ART, and ART simplification strategies are all needed to attain and sustain virological suppression.

AB - Background: In adults with HIV treated with antiretroviral drug regimens from within the three original drug classes (nucleoside or nucleotide reverse transcriptase inhibitors [NRTIs], non-NRTIs [NNRTIs], and protease inhibitors), virological failure occurs slowly, suggesting that long-term virological suppression can be achieved in most people, even in areas where access is restricted to drugs from these classes. It is unclear whether this is the case for children, the group who will need to maintain viral suppression for longest. We aimed to determine the rate and predictors of triple-class virological failure to the three original drugs classes in children. Methods: In the Collaboration of Observational HIV Epidemiological Research Europe, the rate of triple-class virological failure was studied in children infected perinatally with HIV who were aged less than 16 years, starting antiretroviral therapy (ART) with three or more drugs, between 1998 and 2008. We used Kaplan-Meier and Cox regression methods to investigate the risk and predictors of triple-class virological failure after ART initiation. Findings: Of 1007 children followed up for a median of 4.2 (IQR 2.4-6.5) years, 237 (24%) were triple-class exposed and 105 (10%) had triple-class virological failure, of whom 29 never had a viral-load measurement less than 500 copies per mL. Incidence of triple-class virological failure after ART initiation increased with time, and risk by 5 years after ART initiation was 12.0% (95% CI 9.4-14.6). In multivariate analysis, older age at ART initiation was associated with increased risk of failure (p=0.02). Of 686 children starting ART with NRTIs and either a NNRTI or ritonavir-boosted protease inhibitor, the rate of failure was higher than in adults with heterosexually transmitted HIV (hazard ratio 2.2 [95% CI 1.6-3.0, p<0.0001]). Interpretation: Findings highlight the challenges of attaining long-term viral suppression in children who will be taking life-long ART. Early identification of children not responding to ART, adherence support, particularly for children and adolescents aged 13 years or older starting ART, and ART simplification strategies are all needed to attain and sustain virological suppression.

UR - http://www.scopus.com/inward/record.url?scp=79955687620&partnerID=8YFLogxK

U2 - 10.1016/S0140-6736(11)60208-0

DO - 10.1016/S0140-6736(11)60208-0

M3 - Article

C2 - 21511330

AN - SCOPUS:79955687620

SN - 0140-6736

VL - 377

SP - 1580

EP - 1587

JO - The Lancet

JF - The Lancet

IS - 9777

ER -

Risk of triple-class virological failure in children with HIV: a retrospective cohort study

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