Underdosing of antiretrovirals in UK and Irish children with HIV as an example of problems in prescribing medicines to children, 1997-2005: cohort study.
OBJECTIVE
To measure the extent of underdosing of antiretroviral drugs in children.


METHODS
Multicentre cohort study.


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


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


METHODS
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.
Menson
Esse N
EN
MRC Clinical Trials Unit, London NW1 2DA.
Walker
A Sarah
AS
Sharland
Mike
M
Wells
Carole
C
Tudor-Williams
Gareth
G
Riordan
F Andrew I
FA
Lyall
E G Hermione
EG
Gibb
Diana M
DM
D019380:Anti-HIV Agents / Q000008:administration & dosage*; D044966:Anti-Retroviral Agents / Q000008:administration & dosage*; D001827:Body Height; D001835:Body Weight; D002648:Child; D002675:Child, Preschool; D015331:Cohort Studies; D015658:HIV Infections / Q000188:drug therapy*; D006801:Humans; D007223:Infant; D007494:Ireland; D006113:United Kingdom
D019380:Anti-HIV Agents; D044966:Anti-Retroviral Agents