Lopinavir dosing in HIV-infected children in the United Kingdom and Ireland.
BACKGROUND
Uncertainty surrounds the correct dosing of lopinavir/r (LPV/r) in HIV-infected children not receiving non-nucleoside reverse transcriptase inhibitors. The licensed total daily dose is 460 mg/m², whereas the original study, reporting excellent viral load (VL) suppression, used a higher 600 mg/m² dose.


METHODS
We calculated LPV/r daily doses prescribed from 2000 to 2009 within the UK/Irish national Collaborative HIV Paediatric Study (CHIPS) cohort. Logistic and binomial mixed models were used to explore whether higher LPV/r doses affected VL suppression.


RESULTS
Four hundred forty-four of 1201 (37%) children on antiretroviral therapy in CHIPS had taken lopinavir/r without non-nucleoside reverse transcriptase inhibitors. Of 1065 recorded doses, 48% were syrup, 27% capsules and 25% tablets. Ten percent of doses were >10% below 460 mg/m² per day, and 12% were >10% above 600 mg/m². In multivariable models, predictors of lower doses were: once versus twice daily dosing (32 mg/m² lower); syrup versus tablets/capsules (33 mg/m² lower); higher weight-for-age and height-for-age (24 mg/m² and 13 mg/m² lower per unit higher, respectively); and older age (13 mg/m lower per year older for those aged >10 years, P < 0.05). Dosing varied widely by hospital (P = 0.0004), with some targeting higher and others lower doses. For those receiving lopinavir/r for ≥6 months, there was a greater chance of VL <400 copies/mL with higher doses (odds ratio = 1.15 [95% confidence interval: 1.06-1.25 per 50 mg/m² higher], P = 0.001).


CONCLUSIONS
Findings suggest substantial variation and large hospital-level effects in the LPV/r dose prescribed to HIV-infected children in the United Kingdom/Ireland. Higher doses appeared to improve long-term VL suppression, which may be critical in children who need life-long therapy. Results highlight the importance of optimizing dosing in HIV-infected children of all ages.
MRC Clinical Trials Unit, London, United Kingdom.
Katherine
K
Donegan
Katja
K
Doerholt
Ali
A
Judd
Hermione
H
Lyall
Esse
E
Menson
Karina
K
Butler
Pat
P
Tookey
Andrew
A
Riordan
Delane
D
Shingadia
Gareth
G
Tudor-Williams
Di M
DM
Gibb
A Sarah
AS
Walker
D019380:Anti-HIV Agents / Q000008:administration & dosage*; D016009:Chi-Square Distribution; D002648:Child; D002675:Child, Preschool; D015331:Cohort Studies; D005260:Female; D015658:HIV Infections / Q000188:drug therapy* / Q000453:epidemiology / Q000821:virology; D006801:Humans; D007223:Infant; D007494:Ireland / Q000453:epidemiology; D061466:Lopinavir / Q000008:administration & dosage*; D008297:Male; D019438:Ritonavir / Q000008:administration & dosage; D006113:United Kingdom / Q000453:epidemiology; D019562:Viral Load
D019380:Anti-HIV Agents; D061466:Lopinavir; D019438:Ritonavir