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Underdosing of antiretrovirals in UK and Irish children with HIV as an example of problems in prescribing medicines to children, 1997-2005: cohort study

BMJ 2006; 332 doi: https://doi.org/10.1136/bmj.332.7551.1183 (Published 18 May 2006) Cite this as: BMJ 2006;332:1183
  1. Esse N Menson, specialist registrar in paediatric infectious diseases1,
  2. A Sarah Walker, senior statistician1,
  3. Mike Sharland, consultant in paediatric infectious diseases2,
  4. Carole Wells, consultant paediatric HIV pharmacist2,
  5. Gareth Tudor-Williams, consultant paediatric HIV pharmacist, consultant in paediatric infectious diseases3,
  6. F Andrew I Riordan,
  7. E G Hermione Lyall, consultant in paediatric infectious diseases3,
  8. Diana M Gibb, professor of epidemiology, collaborative HIV paediatric study steering committee1
  1. 1 MRC Clinical Trials Unit, London NW1 2DA
  2. 2 St George's Hospital NHS Trust, London SW17 0QT
  3. 3 St Mary's Hospital NHS Trust, London W2 1NY
  • Accepted 6 March 2006

Abstract

Objective To measure the extent of underdosing of antiretroviral drugs in children.

Design Multicentre cohort study.

Setting Clinical centres in hospitals in the United Kingdom and Ireland in the collaborative HIV paediatric study (CHIPS).

Participants 615 HIV infected children aged 2-12 years receiving antiretrovirals.

Main outcome measures Doses relative to weight and height compared with current recommended doses in 2004 European guidelines.

Results The CHIPS cohort of 934 children comprises 80% of diagnosed HIV infected children in the UK and Ireland between January 1997 and March 2005, of which 66% (615) aged 2-12 years were prescribed antiretrovirals. Actual doses standardised to weight or surface area varied widely across individual drugs, antiretroviral class, and calendar time, with children underdosed (prescribed less than 90% of current recommended doses) from 6-62% child time at risk. Three serious issues in prescribing antiretrovirals, which may also be relevant to paediatric prescribing in general, were identified. Firstly, dosing was inadequate before incorrect recommendations at licensing were later revised when important pharmacokinetic results emerged. Secondly, guidelines stating dosage alternatives (by weight/surface area) for the same drug led to different and inconsistent doses. And, thirdly, ongoing growth was not adjusted for.

Conclusions Largely inadvertently, HIV infected children in the United Kingdom and Ireland have been underdosed with antiretrovirals, highlighting problems applicable throughout paediatric prescribing.

Footnotes

  • Embedded ImageTable A, showing the recommended doses, and a list of the committees and participants is on bmj.com

  • Contributors All authors contributed to the writing up of the study. In addition, ENM, ASW, MS, and DMG contributed to the design; ENM and CW collected and collated data; and ASW carried out the analysis. All involvement was on behalf of the collaborative HIV paediatric study steering committee. DMG is guarantor.

  • Funding CHIPS is funded by the London HIV Consortium and in the past has received additional support from Bristol-Myers Squibb, Boehringer Ingelheim, GlaxoSmithKline, Roche, Abbott, and Gilead

  • Competing interests None declared.

  • Ethical approval UK multicentre research ethics committee and relevant local research ethic committees.

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