Long-term virological outcome in children on antiretroviral therapy in the UK and Ireland

Trinh Duong; Ali Judd; Intira Jeannie Collins; Katja Doerholt; Hermione Lyall; Caroline Foster; Karina Butler; Pat Tookey; Delane Shingadia; Esse Menson; David T. Dunn; Di M. Gibb; J. Kenny; K. Bellenger; T. Childs; D. Dobson; D. Johnson; A. Tostevin; A. S. Walker; L. Walker-Nthenda; P. A. Tookey; A. Walsh.; S. Scott; Y. Vaughan; S. Welch; N. Laycock; J. Bernatoniene; A. Finn; P. Lewis; C. Doherty; S. Hawkins; A. McCabe; C. Murphy; T. Tan; J. Daniels; E. Kerr; A. Smyth; S. Christie; A. Gordon; L. Jones; C. Benson; A. Riddell; N. Brown; J. Hancock; S. Gorman; D. Scott; P. McMaster; J. Evans; T. Gardiner; K. Gardiner; The Collaborative HIV Paediatric Study Steering Committee

doi:10.1097/QAD.0000000000000438

Long-term virological outcome in children on antiretroviral therapy in the UK and Ireland

Trinh Duong
, Ali Judd^*
, Intira Jeannie Collins
, Katja Doerholt
, Hermione Lyall
, Caroline Foster
, Karina Butler
, Pat Tookey
, Delane Shingadia
, Esse Menson
, David T. Dunn
, Di M. Gibb
, J. Kenny
, K. Bellenger
, T. Childs
, D. Dobson
, D. Johnson
, A. Tostevin
, A. S. Walker
, L. Walker-Nthenda

P. A. Tookey, A. Walsh., S. Scott, Y. Vaughan, S. Welch, N. Laycock, J. Bernatoniene, A. Finn, P. Lewis, C. Doherty, S. Hawkins, A. McCabe, C. Murphy, T. Tan, J. Daniels, E. Kerr, A. Smyth, S. Christie, A. Gordon, L. Jones, C. Benson, A. Riddell, N. Brown, J. Hancock, S. Gorman, D. Scott, P. McMaster, J. Evans, T. Gardiner, K. Gardiner, The Collaborative HIV Paediatric Study Steering Committee

^*Corresponding author for this work

School of Medicine, Dentistry and Biomedical Sciences

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

36 Citations (Scopus)

27 Downloads (Pure)

Abstract

Objective: To assess factors at the start of antiretroviral therapy (ART) associated with long-term virological response in children.

Design: Multicentre national cohort.

Methods: Factors associated with viral load below 400copies/ml by 12 months and virologic failure among children starting 3/4-drug ART in the UK/Irish Collaborative HIV Paediatric Study were assessed using Poisson models.

Results: Nine hundred and ninety-seven children started ART at a median age of 7.7 years (inter-quartile range 2.9-11.7), 251 (25%) below 3 years: 411 (41%) with efavirenz and two nucleoside reverse transcriptase inhibitors (EFV + 2NRTIs), 264 (26%) with nevirapine and two NRTIs (NVP + 2NRTIs), 119 (12%; 106 NVP, 13 EFV) with non-nucleoside reverse transcriptase inhibitor and three NRTIs (NNRTI+ 3NRTIs), and 203 (20%) with boosted protease inhibitor-based regimens. Median follow-up after ART initiation was 5.7 (3.0-8.8) years. Viral load was less than 400copies/ml by 12 months in 92% [95% confidence interval (CI) 91-94%] of the children. Time to suppression was similar across regimens (P = 0.10), but faster over calendar time, with older age and lower baseline viral load. Three hundred and thirtynine (34%) children experienced virological failure. Although progression to failure varied by regimen (P<0.001) and was fastest for NVP + 2NRTIs regimens, risk after 2 years on therapy was similar for EFV + 2NRTIs and NVP + 2NRTIs, and lowest for NNRTI+3NRTIs regimens (P-interaction = 0.03). Older age, earlier calendar periods and maternal ART exposure were associated with increased failure risk. Early treatment discontinuation for toxicity occurred more frequently for NVP-based regimens, but 5-year cumulative incidence was similar: 6.1% (95% CI 3.9-8.9%) NVP, 8.3% (95% CI 5.6-11.6) EFV, and 9.8% (95% CI 5.7-15.3%) protease inhibitor-based regimens (P = 0.48).

Conclusion: Viral load suppression by 12 months was high with all regimens. NVP + 3NRTIs regimens were particularly efficacious in the longer term and may be a good alternative to protease inhibitor-based ART in young children.

Original language	English
Pages (from-to)	2395-2405
Number of pages	11
Journal	AIDS
Volume	28
Issue number	16
DOIs	https://doi.org/10.1097/QAD.0000000000000438
Publication status	Published - 23 Oct 2014

UN SDGs

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

SDG 3 Good Health and Well-being

Keywords

Antiretroviral therapy
Children
HIV
UK/Ireland
Virological outcome

ASJC Scopus subject areas

Immunology and Allergy
Immunology
Infectious Diseases

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10.1097/QAD.0000000000000438Licence: CC BY-NC-ND

Long-term virological outcome in children on antiretroviral therapy in the UK and Ireland
© 2014 The Authors. This open access manuscript is distributed under a Creative Commons Attribution-NonCommercial-NoDerivs License (https://creativecommons.org/licenses/by-nc-nd/4.0/), which permits distribution and reproduction for non-commercial purposes, provided the author and source are cited.
Final published version, 314 KBLicence: CC BY-NC-ND

Cross-dataset transcription-based quality control for tumour samples and pre-clinical models
Brown, N. (Author), Kennedy, R. (Supervisor) & Blayney, J. (Supervisor), Jul 2024
Student thesis: Doctoral Thesis › Doctor of Philosophy

Cite this

Duong, T., Judd, A., Collins, I. J., Doerholt, K., Lyall, H., Foster, C., Butler, K., Tookey, P., Shingadia, D., Menson, E., Dunn, D. T., Gibb, D. M., Kenny, J., Bellenger, K., Childs, T., Dobson, D., Johnson, D., Tostevin, A., Walker, A. S., ... The Collaborative HIV Paediatric Study Steering Committee (2014). Long-term virological outcome in children on antiretroviral therapy in the UK and Ireland. AIDS, 28(16), 2395-2405. https://doi.org/10.1097/QAD.0000000000000438

@article{fe86e0a9c93e402ca310e105532bc28c,

title = "Long-term virological outcome in children on antiretroviral therapy in the UK and Ireland",

abstract = "Objective: To assess factors at the start of antiretroviral therapy (ART) associated with long-term virological response in children.Design: Multicentre national cohort.Methods: Factors associated with viral load below 400copies/ml by 12 months and virologic failure among children starting 3/4-drug ART in the UK/Irish Collaborative HIV Paediatric Study were assessed using Poisson models.Results: Nine hundred and ninety-seven children started ART at a median age of 7.7 years (inter-quartile range 2.9-11.7), 251 (25\%) below 3 years: 411 (41\%) with efavirenz and two nucleoside reverse transcriptase inhibitors (EFV + 2NRTIs), 264 (26\%) with nevirapine and two NRTIs (NVP + 2NRTIs), 119 (12\%; 106 NVP, 13 EFV) with non-nucleoside reverse transcriptase inhibitor and three NRTIs (NNRTI+ 3NRTIs), and 203 (20\%) with boosted protease inhibitor-based regimens. Median follow-up after ART initiation was 5.7 (3.0-8.8) years. Viral load was less than 400copies/ml by 12 months in 92\% [95\% confidence interval (CI) 91-94\%] of the children. Time to suppression was similar across regimens (P = 0.10), but faster over calendar time, with older age and lower baseline viral load. Three hundred and thirtynine (34\%) children experienced virological failure. Although progression to failure varied by regimen (P<0.001) and was fastest for NVP + 2NRTIs regimens, risk after 2 years on therapy was similar for EFV + 2NRTIs and NVP + 2NRTIs, and lowest for NNRTI+3NRTIs regimens (P-interaction = 0.03). Older age, earlier calendar periods and maternal ART exposure were associated with increased failure risk. Early treatment discontinuation for toxicity occurred more frequently for NVP-based regimens, but 5-year cumulative incidence was similar: 6.1\% (95\% CI 3.9-8.9\%) NVP, 8.3\% (95\% CI 5.6-11.6) EFV, and 9.8\% (95\% CI 5.7-15.3\%) protease inhibitor-based regimens (P = 0.48).Conclusion: Viral load suppression by 12 months was high with all regimens. NVP + 3NRTIs regimens were particularly efficacious in the longer term and may be a good alternative to protease inhibitor-based ART in young children.",

keywords = "Antiretroviral therapy, Children, HIV, UK/Ireland, Virological outcome",

author = "Trinh Duong and Ali Judd and Collins, \{Intira Jeannie\} and Katja Doerholt and Hermione Lyall and Caroline Foster and Karina Butler and Pat Tookey and Delane Shingadia and Esse Menson and Dunn, \{David T.\} and Gibb, \{Di M.\} and J. Kenny and K. Bellenger and T. Childs and D. Dobson and D. Johnson and A. Tostevin and Walker, \{A. S.\} and L. Walker-Nthenda and Tookey, \{P. A.\} and A. Walsh. and S. Scott and Y. Vaughan and S. Welch and N. Laycock and J. Bernatoniene and A. Finn and P. Lewis and C. Doherty and S. Hawkins and A. McCabe and C. Murphy and T. Tan and J. Daniels and E. Kerr and A. Smyth and S. Christie and A. Gordon and L. Jones and C. Benson and A. Riddell and N. Brown and J. Hancock and S. Gorman and D. Scott and P. McMaster and J. Evans and T. Gardiner and K. Gardiner and \{The Collaborative HIV Paediatric Study Steering Committee\}",

year = "2014",

month = oct,

day = "23",

doi = "10.1097/QAD.0000000000000438",

language = "English",

volume = "28",

pages = "2395--2405",

journal = "AIDS",

issn = "0269-9370",

publisher = "Lippincott Williams and Wilkins",

number = "16",

}

Duong, T, Judd, A, Collins, IJ, Doerholt, K, Lyall, H, Foster, C, Butler, K, Tookey, P, Shingadia, D, Menson, E, Dunn, DT, Gibb, DM, Kenny, J, Bellenger, K, Childs, T, Dobson, D, Johnson, D, Tostevin, A, Walker, AS, Walker-Nthenda, L, Tookey, PA, Walsh., A, Scott, S, Vaughan, Y, Welch, S, Laycock, N, Bernatoniene, J, Finn, A, Lewis, P, Doherty, C, Hawkins, S, McCabe, A, Murphy, C, Tan, T, Daniels, J, Kerr, E, Smyth, A, Christie, S, Gordon, A, Jones, L, Benson, C, Riddell, A, Brown, N, Hancock, J, Gorman, S , Scott, D , McMaster, P, Evans, J, Gardiner, T, Gardiner, K & The Collaborative HIV Paediatric Study Steering Committee 2014, 'Long-term virological outcome in children on antiretroviral therapy in the UK and Ireland', AIDS, vol. 28, no. 16, pp. 2395-2405. https://doi.org/10.1097/QAD.0000000000000438

TY - JOUR

T1 - Long-term virological outcome in children on antiretroviral therapy in the UK and Ireland

AU - Duong, Trinh

AU - Judd, Ali

AU - Collins, Intira Jeannie

AU - Doerholt, Katja

AU - Lyall, Hermione

AU - Foster, Caroline

AU - Butler, Karina

AU - Tookey, Pat

AU - Shingadia, Delane

AU - Menson, Esse

AU - Dunn, David T.

AU - Gibb, Di M.

AU - Kenny, J.

AU - Bellenger, K.

AU - Childs, T.

AU - Dobson, D.

AU - Johnson, D.

AU - Tostevin, A.

AU - Walker, A. S.

AU - Walker-Nthenda, L.

AU - Tookey, P. A.

AU - Walsh., A.

AU - Scott, S.

AU - Vaughan, Y.

AU - Welch, S.

AU - Laycock, N.

AU - Bernatoniene, J.

AU - Finn, A.

AU - Lewis, P.

AU - Doherty, C.

AU - Hawkins, S.

AU - McCabe, A.

AU - Murphy, C.

AU - Tan, T.

AU - Daniels, J.

AU - Kerr, E.

AU - Smyth, A.

AU - Christie, S.

AU - Gordon, A.

AU - Jones, L.

AU - Benson, C.

AU - Riddell, A.

AU - Brown, N.

AU - Hancock, J.

AU - Gorman, S.

AU - Scott, D.

AU - McMaster, P.

AU - Evans, J.

AU - Gardiner, T.

AU - Gardiner, K.

AU - The Collaborative HIV Paediatric Study Steering Committee

PY - 2014/10/23

Y1 - 2014/10/23

N2 - Objective: To assess factors at the start of antiretroviral therapy (ART) associated with long-term virological response in children.Design: Multicentre national cohort.Methods: Factors associated with viral load below 400copies/ml by 12 months and virologic failure among children starting 3/4-drug ART in the UK/Irish Collaborative HIV Paediatric Study were assessed using Poisson models.Results: Nine hundred and ninety-seven children started ART at a median age of 7.7 years (inter-quartile range 2.9-11.7), 251 (25%) below 3 years: 411 (41%) with efavirenz and two nucleoside reverse transcriptase inhibitors (EFV + 2NRTIs), 264 (26%) with nevirapine and two NRTIs (NVP + 2NRTIs), 119 (12%; 106 NVP, 13 EFV) with non-nucleoside reverse transcriptase inhibitor and three NRTIs (NNRTI+ 3NRTIs), and 203 (20%) with boosted protease inhibitor-based regimens. Median follow-up after ART initiation was 5.7 (3.0-8.8) years. Viral load was less than 400copies/ml by 12 months in 92% [95% confidence interval (CI) 91-94%] of the children. Time to suppression was similar across regimens (P = 0.10), but faster over calendar time, with older age and lower baseline viral load. Three hundred and thirtynine (34%) children experienced virological failure. Although progression to failure varied by regimen (P<0.001) and was fastest for NVP + 2NRTIs regimens, risk after 2 years on therapy was similar for EFV + 2NRTIs and NVP + 2NRTIs, and lowest for NNRTI+3NRTIs regimens (P-interaction = 0.03). Older age, earlier calendar periods and maternal ART exposure were associated with increased failure risk. Early treatment discontinuation for toxicity occurred more frequently for NVP-based regimens, but 5-year cumulative incidence was similar: 6.1% (95% CI 3.9-8.9%) NVP, 8.3% (95% CI 5.6-11.6) EFV, and 9.8% (95% CI 5.7-15.3%) protease inhibitor-based regimens (P = 0.48).Conclusion: Viral load suppression by 12 months was high with all regimens. NVP + 3NRTIs regimens were particularly efficacious in the longer term and may be a good alternative to protease inhibitor-based ART in young children.

AB - Objective: To assess factors at the start of antiretroviral therapy (ART) associated with long-term virological response in children.Design: Multicentre national cohort.Methods: Factors associated with viral load below 400copies/ml by 12 months and virologic failure among children starting 3/4-drug ART in the UK/Irish Collaborative HIV Paediatric Study were assessed using Poisson models.Results: Nine hundred and ninety-seven children started ART at a median age of 7.7 years (inter-quartile range 2.9-11.7), 251 (25%) below 3 years: 411 (41%) with efavirenz and two nucleoside reverse transcriptase inhibitors (EFV + 2NRTIs), 264 (26%) with nevirapine and two NRTIs (NVP + 2NRTIs), 119 (12%; 106 NVP, 13 EFV) with non-nucleoside reverse transcriptase inhibitor and three NRTIs (NNRTI+ 3NRTIs), and 203 (20%) with boosted protease inhibitor-based regimens. Median follow-up after ART initiation was 5.7 (3.0-8.8) years. Viral load was less than 400copies/ml by 12 months in 92% [95% confidence interval (CI) 91-94%] of the children. Time to suppression was similar across regimens (P = 0.10), but faster over calendar time, with older age and lower baseline viral load. Three hundred and thirtynine (34%) children experienced virological failure. Although progression to failure varied by regimen (P<0.001) and was fastest for NVP + 2NRTIs regimens, risk after 2 years on therapy was similar for EFV + 2NRTIs and NVP + 2NRTIs, and lowest for NNRTI+3NRTIs regimens (P-interaction = 0.03). Older age, earlier calendar periods and maternal ART exposure were associated with increased failure risk. Early treatment discontinuation for toxicity occurred more frequently for NVP-based regimens, but 5-year cumulative incidence was similar: 6.1% (95% CI 3.9-8.9%) NVP, 8.3% (95% CI 5.6-11.6) EFV, and 9.8% (95% CI 5.7-15.3%) protease inhibitor-based regimens (P = 0.48).Conclusion: Viral load suppression by 12 months was high with all regimens. NVP + 3NRTIs regimens were particularly efficacious in the longer term and may be a good alternative to protease inhibitor-based ART in young children.

KW - Antiretroviral therapy

KW - Children

KW - HIV

KW - UK/Ireland

KW - Virological outcome

U2 - 10.1097/QAD.0000000000000438

DO - 10.1097/QAD.0000000000000438

M3 - Article

C2 - 25389551

AN - SCOPUS:84916204586

SN - 0269-9370

VL - 28

SP - 2395

EP - 2405

JO - AIDS

JF - AIDS

IS - 16

ER -

Long-term virological outcome in children on antiretroviral therapy in the UK and Ireland

Abstract

UN SDGs

Keywords

ASJC Scopus subject areas

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Student theses

Cross-dataset transcription-based quality control for tumour samples and pre-clinical models

Cite this