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/m, whereas the original study, reporting excellent viral load (VL) suppression, used a higher 600 mg/m 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/m per day, and 12% were >10% above 600 mg/m. In multivariable models, predictors of lower doses wereonce versus twice daily dosing (32 mg/m lower); syrup versus tablets/capsules (33 mg/m lower); higher weight-for-age and height-for-age (24 mg/m and 13 mg/m 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