T-cell activation and neurodevelopmental outcomes in perinatally HIV-infected children.
T-cell activation and neurodevelopmental outcomes in perinatally HIV-infected children.
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DOI：
10.1097/qad.0b013e328352cee7
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发表时间：
2012-05-15
期刊：
影响因子：
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通讯作者：
Kovacs A
中科院分区：
文献类型：
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作者：
Kapetanovic S;Aaron L;Montepiedra G;Burchett SK;Kovacs A
评估一组围产期HIV感染（HIV感染）的重症儿童随时间推移的基线T细胞活化和神经发育结局。儿科艾滋病临床试验组方案366（PACTG 366）是一项部分随机、开放标签、多中心96周抗逆转录病毒治疗算法研究。通过年龄依赖性评估（Bayley婴儿发育量表-II; Wechsler学龄前和小学智力量表-修订版; Wechsler儿童智力量表-III）测量的神经发育状态是次要结局。使用线性混合模型评估与免疫活化相关的基线和随访神经发育结局，通过研究基线时外周CD 4+和CD 8 + T细胞上的CD 38和人类白细胞抗原（HLA）DR表达进行测量。根据年龄、性别、人种/种族、基线病毒载量、基线CD4%、入组时的巨细胞病毒（CMV）感染状态、研究治疗组、入组时抗逆转录病毒治疗方案的中枢神经系统感染评分和试验后16周的病毒载量反应调整模型。在126例PACTG 366入组者中，年龄至少为1岁，在基线时进行了免疫激活和年龄适当的神经发育评估，其中80例（63%）为非西班牙裔黑人，71例（56%）为男性，122例（97%）正在接受抗逆转录病毒治疗，45例（36%）在入组时为疾病控制和预防中心（CDC）疾病类别C。CD 4 + CD 38 +HLADR+%、CD 4 + CD 38 −HLADR+%和CD 8 + CD 38 +HLADR+%与全面智商评分（FSIQ）呈正相关（斜率分别为0.18、0.70和0.15; P分别为0.02、0.03和0.04）。CD 4 + CD 38 +HLADR−%与FSIQ呈负相关（斜率=−0.16，P =0.01）。与HIV感染的成年人相反，HIV感染的儿童中较高的CD 4 + CD 38 +HLADR+%可能与神经保护作用相关，较高的CD 4 + CD 38+百分比但HLADR− T细胞可能有害。
To evaluate baseline T-cell activation and neurodevelopmental outcomes over time in a cohort of perinatally HIV-infected (PHIV-infected) children with severe disease. Pediatric AIDS Clinical Trials Group protocol 366 (PACTG 366) was a partially randomized, open-label, multicenter 96-week antiretroviral treatment-algorithm study. Neurodevelopmental status, measured by age-dependent evaluations (Bayley scales of infant development-II; Wechsler preschool and primary scale of intelligence-revised; Wechsler intelligence scale for children-III), was a secondary outcome. Linear mixed models were used to assess the baseline and follow-up neurodevelopmental outcomes in relation to immune activation, measured by CD38 and human leukocyte antigen (HLA) DR expression on peripheral CD4+ and CD8+ T cells at study baseline. Models were adjusted for age, sex, race/ethnicity, baseline viral load, baseline CD4%, cytomegalovirus (CMV) infection status at entry, study treatment arms, central nervous system penetrance score of antiretroviral regimen at entry, and viral load response 16 weeks postentry. Among 126 PACTG 366 enrollees who were at least 1 year old and had both immune activation and age-appropriate neurodevelopmental assessments at baseline, 80 (63%) were black non-Hispanic, 71 (56%) males, 122 (97%) were on antiretrovirals, and 45 (36%) were in Centers for Disease Control and Prevention (CDC) disease category C at entry. CD4+CD38+HLADR+%, CD4+CD38−HLADR+%, and CD8+CD38+HLADR+% were positively associated with full-scale Intelligence Quotient scores (FSIQ) (slope =0.18, 0.70, and 0.15, respectively; P =0.02, 0.03, and 0.04, respectively). CD4+CD38+HLADR−% was negatively associated with FSIQ (slope =−0.16, P =0.01). Contrary to HIV-infected adults, in PHIV-infected children higher CD4+CD38+HLADR+% may be associated with a neuroprotective effect and higher percentage of CD4+CD38+ but HLADR− T cells may be deleterious.