van Rossum Annemarie M C, Fraaij Pieter L A, de Groot Ronald
Sophia Children's Hospital, Dr Molewaterplein 60, 3015 GJ Rotterdam, Netherlands.
Lancet Infect Dis. 2002 Feb;2(2):93-102. doi: 10.1016/s1473-3099(02)00183-4.
Although the reduction in HIV-1-related deaths with highly active antiretroviral therapy (HAART) is similar in adults and children, the extent of the changes in two important surrogate markers HIV-1 RNA levels and CD4+ T cell counts, differs widely. In most paediatric studies virological response rates to HAART are inferior to those in adults. This review provides an overview of the paediatric clinical studies using HAART and seeks to improve the understanding of factors that may contribute to success or failure of HAART in children. An overview of all current articles on paediatric clinical trials using HAART is provided. 23 papers were available. HIV-1 RNA loads and CD4+ T cell counts were used as primary outcome measures. Virological response rates were highly variable, both among the different antiretroviral drugs but also among different studies using the same medication. Four studies in which dosages of the administrated protease inhibitor (PI) were adjusted after pharmacokinetic evaluation had superior virological response rates compared with those in which fixed dosages were used. Immunological response rates were more uniform than virological responses. In almost all studies increases of CD4+ T cell counts are reported independent of the extent of the virological response. Side-effects of HAART were generally mild, transient, and of gastrointestinal origin. Significant percentages of patients with serum lipid abnormalities were reported in three paediatric studies. However, signs of clinical lipodystrophy were not observed. The inferior virological response rates, which have been reported in HIV-1 infected children treated with HAART form a reflection of the challenges that are encountered in the treatment of these children. Difficulties with adherence and with the pharmacokinetics of PIs in children require an intensive, child-adjusted approach. A practical approach to therapy in institutions without tertiary care facilities may be induction therapy with a lopinavir containing regimen (lacking a need for therapeutic drug monitoring), to reduce high viral load levels followed by an easily tolerated maintenance regimen, for example containing abacavir or nevirapine.
虽然高效抗逆转录病毒疗法（HAART）降低成人和儿童HIV-1相关死亡的效果相似，但两个重要替代指标——HIV-1 RNA水平和CD4+ T细胞计数的变化程度却有很大差异。在大多数儿科研究中，HAART的病毒学应答率低于成人。本综述概述了使用HAART的儿科临床研究，并试图增进对可能影响儿童HAART治疗成败因素的理解。提供了所有关于使用HAART的儿科临床试验的当前文章概述。共有23篇论文。HIV-1 RNA载量和CD4+ T细胞计数用作主要结局指标。病毒学应答率差异很大，不同抗逆转录病毒药物之间如此，使用相同药物的不同研究之间亦是如此。四项在药代动力学评估后调整所给蛋白酶抑制剂（PI）剂量的研究，其病毒学应答率优于使用固定剂量的研究。免疫学应答率比病毒学应答更一致。几乎在所有研究中，均报告了CD4+ T细胞计数增加，与病毒学应答程度无关。HAART的副作用通常较轻、短暂，且源于胃肠道。三项儿科研究报告了相当比例的血清脂质异常患者。然而，未观察到临床脂肪营养不良的体征。在接受HAART治疗的HIV-1感染儿童中报告的较低病毒学应答率，反映了治疗这些儿童时遇到的挑战。儿童在坚持治疗和PI药代动力学方面的困难需要一种强化的、适合儿童的方法。在没有三级护理设施的机构中，一种实用的治疗方法可能是以含洛匹那韦的方案进行诱导治疗（无需治疗药物监测），以降低高病毒载量水平，随后采用易于耐受的维持方案，例如含阿巴卡韦或奈韦拉平的方案。
