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Pharmacokinetic Optimization of Antiretroviral Therapy in Children and Adolescents

Abstract

There are over 2.1 million HIV-infected children worldwide, who are increasingly exposed to antiretroviral therapy. Given the enormous physiological changes associated with maturation, the role of individualized therapy and optimal dosing in children and adolescents is likely different than in adults. This review summarizes the pharmacodynamics, pharmacokinetics and pharmacogenomics of antiretroviral therapy in children and adolescents, and it discusses the roles of these in the optimization of therapy through the practice of therapeutic drug monitoring/management. Within the pharmacodynamics section are tables and discussion about what is known of the relationships between drug concentrations, inhibitory quotients and effects — both desired and toxic. The pharmacokinetics section summarizes all reported antiretroviral pharmacokinetic data in children, divided into data from population and non-population analytic approaches. Measures of interindividual pharmacokinetic variability are reported. Sampling strategies for the measurement and the interpretation of plasma antiretroviral drug concentrations are suggested, as well as dosing with degrees of renal or hepatic failure. Relevant pharmacogenomic polymorphisms are summarized, and the role for pharmacogenomics testing is discussed. Incorporation of dose adjustment on the basis of measured serum drug concentrations is reviewed, including all such paediatric experience reported in the literature. Discussion of the influences of malnutrition and herbal remedies is also included. Finally, consideration is given to future work in this field.

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Acknowledgements

Michael N. Neely receives support from NIH PHS grants NIAID K23 AI076106, NIBIB R01 EB005803 and NIGMS R01 GM068968. Natella Y. Rakhmanina receives support from NCRR 1K12 RR017613, NICHD K23 1K23HD060452, NIBIB R01 EB005803-01A1 and MO1-RR-020359. The authors have no conflicts of interest that are directly relevant to the content of this review.

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Neely, M., Rakhmanina, N.Y. Pharmacokinetic Optimization of Antiretroviral Therapy in Children and Adolescents. Clin Pharmacokinet 50, 143–189 (2011). https://doi.org/10.2165/11539260-000000000-00000

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Keywords

  • Ritonavir
  • Tenofovir
  • Therapeutic Drug Monitoring
  • Efavirenz
  • Nevirapine