Paediatric Antiretroviral Drug Targets

Amy      Slogrove; Helena      Rabie; Mark      Cotton

Abstract

Introduction: HIV-1 infection is a major problem for children in lower income countries. The benefit of early antiretroviral (ARV) therapy started within 12 weeks of life is well documented. Although the development of new drug classes give alternative options for highly treatment experienced patients there is inadequate pharmacokinetic knowledge regarding the already established ARV classes in infants and children. Also, there are many practical challenges to administering these agents to children. Method and Results: The challenges of current widely available treatment regimens in the light of new vertical transmission prevention guidelines are discussed. The dynamic physiological changes affecting pharmacokinetics in infancy and childhood are reviewed. New antiretroviral drugs in the established drug classes are presented. The new drug classes of entry inhibitors (including co-receptor binding inhibitors and fusion inhibitors), integrase inhibitors and other novel drug classes under development are described and relevant pediatric studies are reviewed. Work on novel drug delivery systems with potential to enhance adherence, improve drug exposure and reduce side-effects are discussed. Conclusion: The established benefits of ARV therapy in children of all ages can be enhanced by appropriate pharmacokinetic data on established antiretroviral agents and child-friendly drug formulations. Besides new suppressive treatment options in treatment experienced patients with multi-class resistant virus the new drug classes provide potential for novel means of disease modification and reduction of vertical transmission. Novel drug classes and delivery systems in development provide potential for further reduction in vertical transmission of HIV, rapid virological suppression and improved neurological outcomes in children and adults.

Keywords: Antiretroviral drugs, Drug targets, Children, HIV-1 infection is, ARV therapy started, ARV classes, inhibitors, integrase inhibitors, pediatric studies, drug delivery systems, multi-class resistant virus, rapid virological suppression, neurological outcomes, antiretroviral therapy, Fixed dose combinations(FDC)