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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.

Original publication

DOI

10.1097/INF.0b013e31827842c9

Type

Journal article

Journal

Pediatr Infect Dis J

Publication Date

01/2013

Volume

32

Pages

45 - 50

Keywords

Anti-HIV Agents, Chi-Square Distribution, Child, Child, Preschool, Cohort Studies, Female, HIV Infections, Humans, Infant, Ireland, Lopinavir, Male, Ritonavir, United Kingdom, Viral Load