Current Research Issues in the Pharmacokinetics of Antiretroviral Drugs in Children

Modern pediatric combination antiretroviral therapy faces a difficult challenge of preserving the focus on an individual child while addressing the globalization of antiretroviral exposure. While the gains from pediatric antiretroviral therapies have been tremendous, minimizing the lag between the approval of new antiretroviral agents in adults and getting these therapies into infants and children, using appropriate formulations and dosages, has been challenging. Fortunately, the development of antiretroviral therapies has coincided with several important initiatives designed to enhance the drug approval process in children. With increased antiretroviral therapy exposure among pediatric patients worldwide, the concerns for long-term adherence, antiretroviral drug resistance and long-term antiretroviral therapy associated toxicities, some of which are only now beginning to be investigated in children, have arisen. This manuscript reviews the major milestones in the evolution and changes in the design of the clinical trials of antiretroviral drugs in HIV-infected children throughout the development of pediatric antiretroviral therapy. It further investigates the role of therapeutic drug monitoring in the clinical trials and clinical practice and discusses challenges of pediatric HIV therapy and antiretroviral drug development