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

J Int AIDS Soc 2008, 11(Suppl 1):08 doi:10.1186/1758-2652-11-S1-08

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 Gibb^1
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

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 overrather than under-dosing when solid formulations cannot achieve exact doses. However, we found no clear evidence that higher doses improved VL suppression.

REFERENCE: [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 Mar;22(3):216-24.

2008-11-10
1758-2652-11-S1-08

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