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

• Published in: BMJ 2006-05, Vol.332 (7551), p.1183-1186
• Main Authors: Menson, Esse N, Walker, A Sarah, Sharland, Mike, Wells, Carole, Tudor-Williams, Gareth, Riordan, F Andrew I, Lyall, E G Hermione, Gibb, Diana M
• Format: Article
• Language: English
• Subjects: Anti-HIV Agents - administration & dosage; Anti-Retroviral Agents - administration & dosage; Antiretroviral drugs; Antiretroviral therapy; Antiretrovirals; Antivirals; Biological and medical sciences; Body Height; Body Weight; Child; Child growth; Child, Preschool; Children; Children & youth; Cohort Studies; Compliance; Dosage; Drug therapy; General aspects; HIV; HIV Infections - drug therapy; Human immunodeficiency virus; Human viral diseases; Humans; Infant; Infectious diseases; Ireland; Medical sciences; Miscellaneous; Pediatrics; Pharmacokinetics; Prescribing; Prescription drugs; Public health. Hygiene; Public health. Hygiene-occupational medicine; Quality of care; Surface areas; United Kingdom; Viral diseases; Viral diseases of the lymphoid tissue and the blood. Aids
• ISSN: 0959-8138; 0959-8146; 0959-535X; 1468-5833; 1756-1833
• DOI: 10.1136/bmj.332.7551.1183

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.