TY - JOUR
T1 - Risk of triple-class virological failure in children with HIV: a retrospective cohort study
AU - Castro, Hannah
AU - Judd, Ali
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 - Pursuing Later Treatment Options II (PLATO II) project team for the Collaboration of Observational HIV Epidemiological Research Europe (COHERE)
N1 - Copyright © 2011 Elsevier Ltd. All rights reserved.
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 identifi cation of children not responding to ART, adherence support, particularly for children and adolescents aged 13 years or older starting ART, and ART simplifi cation 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 identifi cation of children not responding to ART, adherence support, particularly for children and adolescents aged 13 years or older starting ART, and ART simplifi cation strategies are all needed to attain and sustain virological suppression.
KW - Adolescent
KW - Anti-Retroviral Agents
KW - Child
KW - Child, Preschool
KW - Cohort Studies
KW - Female
KW - HIV Infections
KW - Humans
KW - Infant
KW - Infectious Disease Transmission, Vertical
KW - Kaplan-Meier Estimate
KW - Male
KW - Proportional Hazards Models
KW - Retrospective Studies
KW - Risk
KW - Treatment Failure
KW - Viral Load
U2 - 10.1016/S0140-6736(11)60208-0
DO - 10.1016/S0140-6736(11)60208-0
M3 - Journal article
C2 - 21511330
SN - 0140-6736
VL - 377
SP - 1580
EP - 1587
JO - Lancet
JF - Lancet
IS - 9777
ER -
