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-NthendaP. 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

Research output: Contribution to journalArticlepeer-review

33 Citations (Scopus)
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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 languageEnglish
Pages (from-to)2395-2405
Number of pages11
JournalAIDS
Volume28
Issue number16
DOIs
Publication statusPublished - 23 Oct 2014

Keywords

  • Antiretroviral therapy
  • Children
  • HIV
  • UK/Ireland
  • Virological outcome

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Infectious Diseases

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