This article is part of the supplement: Abstracts of the Ninth International Congress on Drug Therapy in HIV Infection .

Oral presentation

O123 To overdose or underdose? The question of Kaletra in children in the UK/Irish Collaborative HIV Paediatric Study (CHIPS)

AS Walker¹, KL Boyd¹, K Doerholt², H Lyall³, E Menson⁴, K Butler⁵, P Tookey⁶, A Riordan⁷, D Shingadia⁸, A Judd¹, G Tudor-Williams³ and DM Gibb¹

¹  MRC Clinical Trials Unit, London, UK

²  Bristol Royal Hospital for Children, Bristol, UK

³  St Mary's Hospital, London, UK

⁴  Evelina Children's Hospital, London, UK

⁵  Our Lady's Hospital for Sick Children, Dublin, Ireland

⁶  Institute of Child Health, London, UK

⁷  Royal Liverpool Children's NHS Trust, Liverpool, UK

⁸  Great Ormond Street Hospital for Sick Children, London, UK

corresponding author email

from Ninth International Congress on Drug Therapy in HIV Infection
Glasgow, UK. 9–13 November 2008

Journal of the International AIDS Society 2008, 11(Suppl 1):O8doi:10.1186/1758-2652-11-S1-O8

The electronic version of this abstract is the complete one and can be found online at: http://www.jiasociety.org/content/11/S1/O8

Published:

10 November 2008

© 2008 Walker et al; licensee BioMed Central Ltd.

Background

The licensed lopinavir/r paediatric total daily dose is 460 mg/m2 without, and 600 mg/m2 with concurrent NNRTIs. The 460 mg/m2 dose without NNRTIs was chosen in preference to 600 mg/m2 in a post-hoc drug-interaction analysis [1]. Excellent VL suppression was also reported (79% <400 c/ml at 48 wks) but was based on the higher 600 mg/m2 dose. Thus, some paediatricians prefer this higher dose regardless of concomitant NNRTI therapy.

Methods

We calculated lopinavir/r doses (mg/m2) prescribed without NNRTIs in the UK/Irish CHIPS cohort from 2000–2007, every time height/weight was measured. We investigated predictors of current dose, including sex; VL and CD4% at the previous visit, current age, CDC stage, height/weight-for-age, calendar year, formulation, frequency and previous PI using mixed models with random effects for child and centre. We considered whether current lopinavir/r dose predicted the next VL being <400 c/ml using binomial mixed models.

Summary of results

311/1,336 (25%) children in CHIPS had ever taken lopinavir/r without NNRTIs, total 654 child-years. Median age at lopinavir/r initiation was 9.0 years (IQR 5.1–12.1). 684 doses were recorded in 299/311 children: 52% were syrup, 38% capsules and 10% tablets, with only 3% once (rather than twice) daily. Dose/m2 could be estimated 2,748 times in 278 children: few (6%) were >10% below the 460 mg/m2 target, and few (9%) >10% above the 600 mg/m2 target, with most >410–<530 mg/m2 (46%) or >530–<660 mg/m2 (39%). In a multivariable model, doses were 17 mg/m2 [95%CI 0–34] higher in children who had prior AIDS, 2 mg/m2 [0–3] higher for every log10 higher VL at the previous visit, 48 mg/m2 [38–58] higher with capsules/tablets vs. syrups, 22 mg/m2 [4–40] higher with twice- vs. once-daily dosing, 19 mg/m2 [15–24] and 10 mg/m2 [6–14] higher for every one unit lower current weight- and height-for-age, respectively, and 9 mg/m2 [5–14] higher for every year younger under 10 (p < 0.05). Dosing varied widely by centre. Adjusting for age, there was no strong evidence that higher doses increased the chance of the next VL being <400 c/ml (OR = 1.10 [0.96–1.25] per 50 mg/m2 higher, p = 0.16) or <50 c/ml (OR = 0.82 [0.73–0.91], p < 0.001).

Conclusion

In summary, younger or stunted/wasted children or those with prior AIDS/higher VLs received higher doses. Doses were higher with capsules/tablets, likely reflecting over- rather than under-dosing when solid formulations cannot achieve exact doses. However, we found no clear evidence that higher doses improved VL suppression.

References

1. Saez-Llorens X, et al.: Forty-eight-week evaluation of lopinavir/ritonavir, a new protease inhibitor, in human immunodeficiency virus-infected children.

   Pediatr Infect Dis J 2003, 22:216-224. PubMed Abstract | Publisher Full Text

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