Slogrove Amy, Rabie Helena, Cotton Mark
Department of Pediatrics and Child Health, Faculty of Health Sciences, Stellenbosch University, Tygerberg, South Africa.
Infect Disord Drug Targets. 2011 Apr;11(2):115-23. doi: 10.2174/187152611795589672.
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.
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.
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.
对于低收入国家的儿童来说，HIV-1感染是一个重大问题。在出生12周内开始进行早期抗逆转录病毒（ARV）治疗的益处已有充分记录。尽管新的药物类别为治疗经验丰富的患者提供了替代选择，但对于婴幼儿和儿童中已有的抗逆转录病毒药物类别，药代动力学知识仍不充分。此外，给儿童使用这些药物还面临许多实际挑战。
根据新的垂直传播预防指南，讨论了当前广泛使用的治疗方案所面临的挑战。回顾了影响婴幼儿和儿童药代动力学的动态生理变化。介绍了已确立药物类别中的新型抗逆转录病毒药物。描述了进入抑制剂（包括共受体结合抑制剂和融合抑制剂）、整合酶抑制剂以及其他正在研发的新型药物类别，并回顾了相关的儿科研究。讨论了有望提高依从性、改善药物暴露并减少副作用的新型药物递送系统的研究进展。
通过关于已确立抗逆转录病毒药物的适当药代动力学数据以及儿童友好型药物制剂，可以增强ARV治疗在各年龄段儿童中的既定益处。除了为具有多类别耐药病毒的治疗经验丰富的患者提供新的抑制性治疗选择外，新的药物类别还为疾病改善和减少垂直传播提供了新的手段。正在研发的新型药物类别和递送系统有可能进一步降低HIV的垂直传播、实现快速病毒学抑制并改善儿童和成人的神经学结局。
