The pharmacology of antiretroviral drugs in pediatric patients

Background: Research has demonstrated the benefits of antiretroviral therapy in children, but problems still exist with drug therapy in this population. Although the pathogenesis of human immunodeficiency virus (HIV) infection and the general virologic and immunologic principles underlying the use of antiretroviral therapy are similar for all patients infected with HIV, there are unique considerations for HIV-infected infants, children, and adolescents. These include changes in pharmacokinetic parameters due to the continuing development and maturation of organ systems involved in drug metabolism and clearance. Objective: This review addresses pediatric pharmacologic characteristics and their effects on specific anstiretroviral drugs used in neonates, infants, and children. Methods: A search of the literature from January 1983 through December 2001 was performed on MEDLINE using the search terms children, neonates, HIV, and pharmacokinetics. Relevant book chapters and conference presentations were also included. Results: The use of antiretroviral drugs in the perinatal period to reduce the risk of HIV transmission during this time poses particular problems. These include the need to modify doses due to physiologic changes in neonates, the potential for adverse short- or long-term effects on the fetus and newborn, and the efficacy of therapy at reducing the risk of perinatal transmission. The plasma concentrations and clearance rates of antiretroviral drugs in children differ from those seen in adults, but only limited data are available. Conclusions: Clinical trials are still needed to determine the optimal dosing schedules of antiretroviral drugs in all age groups. Until such trials are completed, the monitoring of plasma antiretroviral drug concentrations is necessary to assess efficacy and prevent toxicity in neonates, infants, and children.