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Pharmacokinetics of Antiretroviral Therapy in HIV-1-Infected Children

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Abstract

The initiation of antiretroviral therapy has resulted in an impressive reduction in the rate of disease progression in AIDS and HIV-1-related deaths in children; however, there are still several major challenges to be faced in order to improve therapy. A major topic that needs to be dealt with is the establishment of the optimal dosage of antiretroviral therapy for children. This review presents the currently available peer-reviewed data on the pharmacokinetics of nucleoside reverse transcriptase inhibitors (NRTIs), non-nucleoside reverse transcriptase inhibitors (NNRTIs), protease inhibitors (PIs) and fusion inhibitors (FIs) in children. In addition, the data are discussed in relation to the currently available European and US guidelines and the US FDA-approved drug labels.

High intra- and interpatient variability in pharmacokinetics are often observed for all antiretroviral drugs. The number of children included in the pharmacokinetic studies is often small and children are often divided into divergent groups using different dosage levels and/or drug formulations. For a substantial number of antiretroviral drugs, dosage recommendations, especially for young children, are still absent in the European and US guidelines. The recommended drug dosages in the guidelines are often different from that in the officially approved drug product label. In addition, the recommended drug dosages may deviate between the European and US guidelines. Thus, while practioners aim to meet the recommendations in the official guidelines, patients may receive highly divergent dosages of medication.

The high intra- and interpatient variability in pharmacokinetics of antiretroviral drugs in children hampers the application of fixed dosages of antiretroviral drugs. For PIs and NNRTIs, plasma drug levels correlate with viral suppression and drug toxicity. NRTIs are prodrugs that are intracellularly converted to their active triphosphate form and, therefore, plasma NRTI levels correlate poorly with viral suppression. Therapeutic drug monitoring of PIs and NNRTIs should be considered to optimise HIV therapy in children.

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Acknowledgements

The authors have participated in studies that were financially supported by Merck Sharp & Dohme Inc., GlaxoSmithKline and Abbott Laboratories. J.A. van Kampen is currently receiving financial support from Aids Fonds, The Netherlands (project number 2004051). The previously mentioned sponsors were not involved in data collection, data analysis, the writing of this article or article submission. The authors have no other conflicts of interest.

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  1. Department of Pediatrics, Erasmus MC/Sophia Children’s Hospital, Dr Molewaterplein 60, 3015 GJ, Rotterdam, The Netherlands

    Pieter L. A. Fraaij, Jeroen J. A. van Kampen &  Ronald de Groot

  2. Department of Clinical Pharmacy, University Medical Center, Nijmegen, The Netherlands

    David M. Burger

  3. Nijmegen University Center for Infectious Diseases (NUCI), Nijmegen, The Netherlands

    David M. Burger

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  1. Pieter L. A. Fraaij
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Correspondence to Ronald de Groot.

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Fraaij, P.L.A., van Kampen, J.J.A., Burger, D.M. et al. Pharmacokinetics of Antiretroviral Therapy in HIV-1-Infected Children. Clin Pharmacokinet 44, 935–956 (2005). https://doi.org/10.2165/00003088-200544090-00004

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