Two-year clinical and immune outcomes in human immunodeficiency virus-infected children who reconstitute CD4 T cells without control of viral replication after combination antiretroviral therapy
Two-year clinical and immune outcomes in human immunodeficiency virus-infected children who reconstitute CD4 T cells without control of viral replication after combination antiretroviral therapy
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DOI：
10.1542/peds.2004-0274
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发表时间：
2004-11-01
期刊：
影响因子：
8
通讯作者：
Sleasman, JW
中科院分区：
文献类型：
--
作者：
Ghaffari, G;Passalacqua, DJ;Sleasman, JW
目标。目的评价含蛋白水解酶抑制剂的抗逆转录病毒治疗96周的临床和免疫效果。对40名感染人类免疫缺陷病毒(HIV)的儿童进行了前瞻性研究，这些儿童在治疗后24周出现病毒抑制(VS)并成功免疫重建(IS)，未能抑制病毒(VF)或发展免疫重建(IF)，或免疫与病毒反应(VF/IS)不协调。所有登记的儿童每毫升都有4.0log(10)个病毒RNA拷贝，属于疾病控制和预防中心免疫阶段2或3。在接下来的72周内评估临床、病毒和免疫结果。VS/IS组和VF/IS组显示出类似的CD4T细胞持续增加，尽管不协调组的病毒水平在治疗后48周和96周反弹至治疗前水平。与入院时相比，VF/IS结果组的身高和体重z分数显著增加，与VS/IS组相似。治疗后，VF/IS组和VS/IS组在破伤风免疫后的抗原特异性反应相似。VS/IS和VF/IS中HIV相关疾病的患病率均有所下降，但VF/IF反应组中未见下降。研究结果表明，在蛋白水解酶抑制剂的选择性压力下复制的病毒不会像治疗前的病毒那样对T细胞免疫产生有害的影响。在接受高效抗逆转录病毒治疗方案的HIV感染儿童中，与病毒负担相比，CD4T细胞计数可能更好地预测疾病进展和生长改善。
Objective. To evaluate 96-week clinical and immune outcomes to protease inhibitor-containing antiretroviral therapy.Methods. A prospective study was conducted of 40 human immunodeficiency virus (HIV)-infected children who displayed viral suppression ( VS) with successful immune reconstitution ( IS), failure to suppress virus (VF) or develop immune reconstitution ( IF), or discordant immune and viral responses (VF/IS) at 24 weeks posttherapy. All children enrolled had viral RNA >4.0 log(10) copies per mL and were Centers for Disease Control ad Prevention immune stage 2 or 3. Clinical, viral, and immune outcomes were assessed during the subsequent 72 weeks.Results. VS/IS and VF/IS groups displayed similar sustained increases in CD4 T cells, although viral levels rebounded by 48 and 96 weeks posttherapy to pretherapy levels in the discordant group. The VF/IS outcome group had significant increases in height and weight z scores compared with entry and were similar to the VS/IS group. After treatment, antigen-specific responses after tetanus immunization were similar in the VF/IS and VS/IS groups. Prevalence of HIV-associated illnesses decreased in both VS/IS and VF/IS but not in VF/IF response groups.Conclusions. The findings indicate that viral replication under the selective pressure of protease inhibitors fails to exhibit the same deleterious impact on T-cell immunity as pretherapy viruses. CD4 T-cell counts may be a better predictor of disease progression and improvement in growth than viral burden in HIV-infected children who receive a protease inhibitor as part of a highly active antiretroviral therapy regimen.