Malnutrition in HIV-Infected Children Is an Indicator of Severe Disease with an Impaired Response to Antiretroviral Therapy.
Malnutrition in HIV-Infected Children Is an Indicator of Severe Disease with an Impaired Response to Antiretroviral Therapy.
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感染艾滋病毒的儿童营养不良是严重疾病的一个指标，抗逆转录病毒治疗的反应受损。
DOI：
10.1089/aid.2016.0261
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发表时间：
2018-01
影响因子：
1.5
通讯作者：
Archary M
中科院分区：
文献类型：
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作者：
Muenchhoff M;Healy M;Singh R;Roider J;Groll A;Kindra C;Sibaya T;Moonsamy A;McGregor C;Phan MQ;Palma A;Kloverpris H;Leslie A;Bobat R;LaRussa P;Ndung'u T;Goulder P;Sobieszczyk ME;Archary M
这项观察性研究旨在描述有或没有严重急性营养不良（SAM）和hiv感染的儿童的免疫发病机制和治疗结果。在开始抗逆转录病毒治疗（ART）之前，我们研究了32名hiv感染儿童和41名hiv感染儿童（没有SAM）的微生物易位（16sDNA）、肠道损伤（iFABP）、单核细胞活化（sCD14）、t细胞活化（CD38、HLA-DR）和免疫衰竭（PD1）标志物，并将这些儿童与15名hiv感染儿童和19名没有SAM的hiv感染儿童进行了横断面比较。然后，我们前瞻性地测量了这些标记物，并将它们与艾滋病毒感染儿童在开始抗逆转录病毒治疗后48周的治疗结果相关联。分别采用实时荧光定量PCR、ELISA和Luminex检测血浆16sDNA、iFABP和sCD14水平。用流式细胞术检测T细胞表型标记物。多元回归分析采用广义线性模型（GLMs）和最小绝对收缩和选择算子（LASSO）方法进行变量选择。与没有SAM的hiv感染儿童相比，患有SAM的hiv感染儿童的微生物易位、T细胞激活和耗竭增加。在hiv感染的儿童中，微生物易位、免疫激活和衰竭明显增加，但sam状态没有差异。SAM与抗逆转录病毒治疗开始后早期死亡率增加有关。营养不良、年龄、微生物易位、单核细胞和CD8 T细胞活化与抗逆转录病毒治疗48周后CD4%免疫恢复率下降独立相关。SAM与未感染艾滋病毒的儿童中微生物易位增加、免疫激活和免疫衰竭有关，并与接受抗逆转录病毒治疗的感染艾滋病毒的儿童预后较差和免疫恢复受损有关。
This observational study aimed to describe immunopathogenesis and treatment outcomes in children with and without severe acute malnutrition (SAM) and HIV-infection. We studied markers of microbial translocation (16sDNA), intestinal damage (iFABP), monocyte activation (sCD14), T-cell activation (CD38, HLA-DR) and immune exhaustion (PD1) in 32 HIV-infected children with and 41 HIV-infected children without SAM prior to initiation of antiretroviral therapy (ART) and cross-sectionally compared these children to 15 HIV-uninfected children with and 19 HIV-uninfected children without SAM. We then prospectively measured these markers and correlated them to treatment outcomes in the HIV-infected children at 48 weeks following initiation of ART. Plasma levels of 16sDNA, iFABP and sCD14 were measured by quantitative real time PCR, ELISA and Luminex, respectively. T cell phenotype markers were measured by flow cytometry. Multiple regression analysis was performed using generalized linear models (GLMs) and the least absolute shrinkage and selection operator (LASSO) approach for variable selection. Microbial translocation, T cell activation and exhaustion were increased in HIV-uninfected children with SAM compared to HIV-uninfected children without SAM. In HIV-infected children microbial translocation, immune activation, and exhaustion was strongly increased but did not differ by SAM-status. SAM was associated with increased mortality rates early after ART initiation. Malnutrition, age, microbial translocation, monocyte, and CD8 T cell activation were independently associated with decreased rates of CD4% immune recovery after 48 weeks of ART. SAM is associated with increased microbial translocation, immune activation, and immune exhaustion in HIV-uninfected children and with worse prognosis and impaired immune recovery in HIV-infected children on ART.