Immunologic and virologic responses to HAART in severely immunocompromised HIV-1-infected children.
Immunologic and virologic responses to HAART in severely immunocompromised HIV-1-infected children.
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严重免疫功能低下的 HIV-1 感染儿童对 HAART 的免疫学和病毒学反应。
DOI：
10.1097/00002030-199912240-00005
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发表时间：
1999
期刊：
影响因子：
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通讯作者：
Borkowsky,W
中科院分区：
文献类型：
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作者：
Essajee,SM;Kim,M;Gonzalez,C;Rigaud,M;Kaul,A;Chandwani,S;Hoover,W;Lawrence,R;Spiegel,H;Pollack,H;Krasinski,K;Borkowsky,W
目的：确定高效抗逆转录病毒疗法（HAART）对儿童艾滋病患者的长期免疫学和病毒学影响。设计：一项前瞻性观察研究。设置：两个儿科HIV诊所。参与者：25名未接受过蛋白酶抑制剂治疗的HIV感染儿童（年龄2-18岁），患有晚期疾病（CD 4 ≤ 6%）。干预：HAART（一种蛋白酶抑制剂和一种或多种核苷类似物）。白喉和破伤风免疫接种后18个月的therapy.Main结果measurements：在CD 4细胞和血浆HIV-1 RNA水平的百分比的变化;淋巴细胞增殖反应回忆抗原治疗后测定; CD 4细胞记忆phenotype.Results：随访的中位持续时间为18.8个月（范围，7.5-28个月）。基线时，CD 4细胞百分比为2%（范围，0-6%），12个月时显著增加至高于基线的16%（范围，3-48%）（P= 0.002）。平均最大CD 4细胞增加为20.7%（范围4-48%），相当于高于基线657× 10 6个细胞/l（范围30-2240× 10 6个细胞/l）。相比之下，中位病毒载量在12个月时并没有显著低于基线（P= 0.34），只有25%的患者持续检测不到病毒载量。重建的CD 4细胞70%是幼稚的，没有一个受试者对破伤风和白喉有淋巴增殖反应，尽管40%的受试者对念珠菌（一种环境抗原）有反应。一个单一的免疫接种白喉和破伤风类毒素产生淋巴细胞增殖反应破伤风在三出6 patients.Conclusions：HAART与持续增加的CD 4细胞计数，尽管“病毒学失败”的发生率很高。CD 4计数和幼稚细胞的比例高于成人中的报告，这可能反映了儿童中更大的胸腺活性。在没有额外抗原暴露的情况下，不能扩增过去遇到的在治疗前不普遍的抗原的记忆细胞克隆。
Objective:To determine the long-term immunologic and virologic effects of highly active antiretroviral therapy (HAART) in children with AIDS.Design:A prospective observational study.Setting:Two pediatric HIV clinics.Participants:Twenty-five protease-inhibitor naive HIV-infected children (aged 2-18 years) with advanced disease (CD4≤ 6%).Intervention:HAART (one protease inhibitor and one or more nucleoside analogs). Diphtheria and tetanus immunization in six patients after 18 months of therapy.Main outcome measures:Changes in percentage of CD4 cells and plasma HIV-1 RNA levels; post-treatment assays of lymphoproliferative responses to recall antigens; CD4 cell memory phenotype.Results:Median duration of follow-up was 18.8 months (range, 7.5-28 months). At baseline the CD4 cell percentage was 2%(range, 0-6%), this increased significantly to 16%(range, 3-48%) above baseline at 12 months (P= 0.002). The mean maximum CD4 cell increase was 20.7%(range 4-48%) which corresponds to 657× 10 6 cells/l (range, 30-2240× 10 6 cells/l) above baseline. By contrast, the median viral load was not significantly lower at 12 months than at baseline (P= 0.34), and only 25% of the patients had sustained undetectable viral load. Of the reconstituted CD4 cells 70% were naive, and none of the subjects had lymphoproliferative responses to tetanus and diphtheria although 40% did develop responses to Candida, an environmental antigen. A single immunization with diphtheria and tetanus toxoid produced lymphoproliferative responses to tetanus in three out of six patients.Conclusions:HAART was associated with sustained increases in CD4 cell counts, despite a high incidence of ‚virologic failure ‚. CD4 counts and the proportion of naive cells were higher than have been reported in adults, which may be a reflection of greater thymic activity in children. Memory cell clones for antigens encountered in the past which are not prevalent before therapy could not be expanded without additional antigenic exposure.