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Lopinavir Dosing in HIV-infected Children in the United Kingdom and Ireland

Donegan, Katherine PhD*; Doerholt, Katja MB BS, MSc, MRCPCH*†; Judd, Ali PhD*; Lyall, Hermione MD, FRCPCH; Menson, Esse MB BS, MRCPCH§; Butler, Karina MBBCH; Tookey, Pat PhD; Riordan, Andrew MD, FRCPCH**; Shingadia, Delane MB ChB, FRCPCH††; Tudor-Williams, Gareth MB BS, MRCPCH; Gibb, Di M. MD, FRCPCH*††; Walker, A. Sarah PhD*

The Pediatric Infectious Disease Journal: January 2013 - Volume 32 - Issue 1 - p 45–50
doi: 10.1097/INF.0b013e31827842c9
HIV Reports

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/m2 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.

From the *MRC Clinical Trials Unit; St. George’s Healthcare NHS Trust; Imperial College Healthcare NHS Trust; §Evelina Children’s Hospital, Guy’s and St Thomas’ NHS Trust, London, United Kingdom; Our Lady’s Children’s Hospital, Dublin, Ireland; UCL Institute of Child Health, London; **Alder Hey Children’s NHS Foundation Trust, Liverpool; and ††Great Ormond Street Hospital for Children NHS Trust, London, United Kingdom.

The research leading to these results has received funding from the European Union Seventh Framework Programme (FP7/2007–2013) under grant agreement n° 201057. The National Study of HIV in Pregnancy and Childhood is funded by the Health Protection Agency. The Collaborative HIV Paediatric Study is funded by the NHS (London Specialised Commissioning Group) and has received additional support from Bristol-Myers Squibb, Boehringer Ingelheim, GlaxoSmithKline, Roche, Abbott, and Gilead Sciences. The views expressed in the publication are those of the authors and not necessarily those of the Health Protection Agency, the London NHS Specialised Commissioning Group, the Medical Research Council, or any of the additional funders. The authors have no other funding or conflicts of interest to disclose.

Address for correspondence: Ali Judd, PhD, MRC Clinical Trials Unit, Aviation House, 125 Kingsway, London WC2B 6NH, United Kingdom. E-mail:

Accepted July 25, 2012

© 2013 Lippincott Williams & Wilkins, Inc.