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

Research output: Contribution to journalArticlepeer-review


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 languageEnglish
Pages (from-to)1580-1587
Number of pages8
JournalThe Lancet
Issue number9777
Early online date20 Apr 2011
Publication statusPublished - 7 May 2011

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