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

Pursuing Later Treatment Options II (PLATO II) project team for the Collaboration of Observational HIV Epidemiological Research Europe (COHERE), Hannah Castro, Ali Judd, 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, Dominique Costagliola, Alessandro Cozzi-Lepri, Andrea De Luca, Stephane De Wit, Maria Dorrucci, Xavier Duval, Federico García, Jade Ghosn, Huldrych Günthard, Ali Judd, Bruno Ledergerber, Sergio Lo Caputo, Rebecca Lodwick, Antoni Noguera-Julian, Bernard Masquelier, Laurence Meyer, Amanda Mocroft, Cristina Mussini, Niels Obel, Dimitrios Paraskevis, Roger Paredes, Santiago Pérez-Hoyos, Andrew Phillips, Deenan Pillay, Daniel Podzamczer, José T Ramos, Peter Reiss, Christoph Stephan, Ramón Teira, Claire Thorne, Pat A Tookey, Carlo Torti, Giota Touloumi, Ard van Sighem, Josiane Warsawski, Robert Zangerle, Giota Touloumi, Josiane Warszawski, Laurence Meyer, François Dabis, Murielle Mary Krause, Jade Ghosn, Catherine Leport, Frank de Wolf, Peter Reiss, Maria Prins, Heiner C Bücher, Caroline Sabin, Diana Gibb, Gerd Fätkenheuer, Julia Del Amo, Antoni Noguera-Julian, Niels Obel, Claire Thorne, Amanda Mocroft, Ole Kirk, Christoph Stephan, Santiago Pérez-Hoyos, Andrea Antinori, Antonella d'Arminio Monforte, Pier-Angelo Tovo, Maurizio de Martino, Norbert H Brockmeyer, José T Ramos, Manuel Battegay, Patrick Francioli, Cristina Mussini, Dolors Carnicer-Pont, Pat A Tookey, Jordi Casabona, Jose M Miró, Antonella Castagna, Stephane de Wit, Tessa Goetghebuer, Carlo Torti, Ramon Teira, Myriam Garrido, Nikos Dedes, Ian Weller, Jordi Casabona, Dominique Costagliola, Antonella d'Arminio-Monforte, Bruno Ledergerber, Maria Prins, Frank de Wolf, Jesper Grarup, Genevieve Chene, Fideline Collin-Filleul, Céline Colin, Christine Schwimmer, Michelle Ellefson, Jesper Kjaer, Maria Paulsen, Julia Bohlius, Vincent Bouteloup, Heiner C Bucher, Alessandro Cozzi-Lepri, François Dabis, Antonella d'Arminio Monforte, Frank de Wolf, Maria Prins, Matthias Egger, Hansjakob Furrer, Ole Kirk, Olivier Lambotte, Charlotte Lewden, Rebecca Lodwick, Sophie Matheron, Laurence Meyer, Jose Miro, Amanda Mocroft, Roger Paredes, Andrew Phillips, Massimo Puoti, Joanne Reekie, Caroline Sabin, Colette Smit, Jonathan Sterne, Rodolphe Thiebaut, Claire Thorne, Linda Wittkop, Pursuing Later Treatment Options II (PLATO II) project team for the Collaboration of Observational HIV Epidemiological Research Europe (COHERE), Hannah Castro, Ali Judd, 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, Dominique Costagliola, Alessandro Cozzi-Lepri, Andrea De Luca, Stephane De Wit, Maria Dorrucci, Xavier Duval, Federico García, Jade Ghosn, Huldrych Günthard, Ali Judd, Bruno Ledergerber, Sergio Lo Caputo, Rebecca Lodwick, Antoni Noguera-Julian, Bernard Masquelier, Laurence Meyer, Amanda Mocroft, Cristina Mussini, Niels Obel, Dimitrios Paraskevis, Roger Paredes, Santiago Pérez-Hoyos, Andrew Phillips, Deenan Pillay, Daniel Podzamczer, José T Ramos, Peter Reiss, Christoph Stephan, Ramón Teira, Claire Thorne, Pat A Tookey, Carlo Torti, Giota Touloumi, Ard van Sighem, Josiane Warsawski, Robert Zangerle, Giota Touloumi, Josiane Warszawski, Laurence Meyer, François Dabis, Murielle Mary Krause, Jade Ghosn, Catherine Leport, Frank de Wolf, Peter Reiss, Maria Prins, Heiner C Bücher, Caroline Sabin, Diana Gibb, Gerd Fätkenheuer, Julia Del Amo, Antoni Noguera-Julian, Niels Obel, Claire Thorne, Amanda Mocroft, Ole Kirk, Christoph Stephan, Santiago Pérez-Hoyos, Andrea Antinori, Antonella d'Arminio Monforte, Pier-Angelo Tovo, Maurizio de Martino, Norbert H Brockmeyer, José T Ramos, Manuel Battegay, Patrick Francioli, Cristina Mussini, Dolors Carnicer-Pont, Pat A Tookey, Jordi Casabona, Jose M Miró, Antonella Castagna, Stephane de Wit, Tessa Goetghebuer, Carlo Torti, Ramon Teira, Myriam Garrido, Nikos Dedes, Ian Weller, Jordi Casabona, Dominique Costagliola, Antonella d'Arminio-Monforte, Bruno Ledergerber, Maria Prins, Frank de Wolf, Jesper Grarup, Genevieve Chene, Fideline Collin-Filleul, Céline Colin, Christine Schwimmer, Michelle Ellefson, Jesper Kjaer, Maria Paulsen, Julia Bohlius, Vincent Bouteloup, Heiner C Bucher, Alessandro Cozzi-Lepri, François Dabis, Antonella d'Arminio Monforte, Frank de Wolf, Maria Prins, Matthias Egger, Hansjakob Furrer, Ole Kirk, Olivier Lambotte, Charlotte Lewden, Rebecca Lodwick, Sophie Matheron, Laurence Meyer, Jose Miro, Amanda Mocroft, Roger Paredes, Andrew Phillips, Massimo Puoti, Joanne Reekie, Caroline Sabin, Colette Smit, Jonathan Sterne, Rodolphe Thiebaut, Claire Thorne, Linda Wittkop

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.

Funding: UK Medical Research Council award G0700832.

Copyright © 2011 Elsevier Ltd. All rights reserved.

Figures

Figure 1
Figure 1
Inclusion criteria for initial regimens and definition of triple-class virological failure in the main analysis and the comparison of children with adults TCVF=triple-class virological failure. NRTI=nucleoside or nucleotide reverse transcriptase inhibitors. NNRTI=non-NRTI. PI/r=ritonavir-boosted protease inhibitor. PI=protease inhibitor. uPI=unboosted protease inhibitor.
Figure 2
Figure 2
Incidence per 100 person-years (95% CI) of triple-class virological failure in children with HIV by duration of antiretroviral therapy *At end of year 9.

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Source: PubMed

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