微生物易位不会导致感染 HIV 的乌干达儿童免疫激活。
Microbial Translocation Does Not Drive Immune Activation in Ugandan Children Infected With HIV.
机构信息
Infection, Immunity, and Inflammation Programme.
INSERM, Bordeaux Population Health Research Centre, UMR 1219, University of Bordeaux, ISPED.
出版信息
J Infect Dis. 2019 Jan 1;219(1):89-100. doi: 10.1093/infdis/jiy495.
OBJECTIVE
Immune activation is associated with morbidity and mortality during human immunodeficiency virus (HIV) infection, despite receipt of antiretroviral therapy (ART). We investigated whether microbial translocation drives immune activation in HIV-infected Ugandan children.
METHODS
Nineteen markers of immune activation and inflammation were measured over 96 weeks in HIV-infected Ugandan children in the CHAPAS-3 Trial and HIV-uninfected age-matched controls. Microbial translocation was assessed using molecular techniques, including next-generation sequencing.
RESULTS
Of 249 children included, 142 were infected with HIV; of these, 120 were ART naive, with a median age of 2.8 years (interquartile range [IQR], 1.7-4.0 years) and a median baseline CD4+ T-cell percentage of 20% (IQR, 14%-24%), and 22 were ART experienced, with a median age of 6.5 years (IQR, 5.9-9.2 years) and a median baseline CD4+ T-cell percentage of 35% (IQR, 31%-39%). The control group comprised 107 children without HIV infection. The median increase in the CD4+ T-cell percentage was 17 percentage points (IQR, 12-22 percentage points) at week 96 among ART-naive children, and the viral load was <100 copies/mL in 76% of ART-naive children and 91% of ART-experienced children. Immune activation decreased with ART use. Children could be divided on the basis of immune activation markers into the following 3 clusters: in cluster 1, the majority of children were HIV uninfected; cluster 2 comprised a mix of HIV-uninfected children and HIV-infected ART-naive or ART-experienced children; and in cluster 3, the majority were ART naive. Immune activation was low in cluster 1, decreased in cluster 3, and persisted in cluster 2. Blood microbial DNA levels were negative or very low across groups, with no difference between clusters except for Enterobacteriaceae organisms (the level was higher in cluster 1; P < .0001).
CONCLUSION
Immune activation decreased with ART use, with marker clustering indicating different activation patterns according to HIV and ART status. Levels of bacterial DNA in blood were low regardless of HIV status, ART status, and immune activation status. Microbial translocation did not drive immune activation in this setting.
CLINICAL TRIALS REGISTRATION
ISRCTN69078957.
目的
尽管接受了抗逆转录病毒疗法（ART），但免疫激活仍与人类免疫缺陷病毒（HIV）感染期间的发病率和死亡率相关。我们研究了微生物易位是否会导致 HIV 感染的乌干达儿童的免疫激活。
方法
在 CHAPAS-3 试验中，对 199 名 HIV 感染的乌干达儿童和年龄匹配的未感染 HIV 的对照组进行了 96 周的 19 种免疫激活和炎症标志物的测量。使用包括下一代测序在内的分子技术评估微生物易位。
结果
在纳入的 249 名儿童中，有 142 名感染了 HIV；其中，120 名是未经 ART 治疗的初治儿童，中位年龄为 2.8 岁（四分位距 [IQR]，1.7-4.0 岁），中位基线 CD4+T 细胞百分比为 20%（IQR，14%-24%），22 名是接受过 ART 治疗的儿童，中位年龄为 6.5 岁（IQR，5.9-9.2 岁），中位基线 CD4+T 细胞百分比为 35%（IQR，31%-39%）。对照组由 107 名未感染 HIV 的儿童组成。初治儿童在第 96 周时，CD4+T 细胞百分比的中位数增加了 17 个百分点（IQR，12-22 个百分点），76%的初治儿童和 91%的接受过 ART 治疗的儿童的病毒载量<100 拷贝/ml。免疫激活随着 ART 的使用而减少。根据免疫激活标志物，儿童可分为以下 3 个聚类：在聚类 1 中，大多数儿童未感染 HIV；聚类 2 包含混合了未感染 HIV 的儿童以及未感染 HIV 的初治和接受过 ART 治疗的儿童；聚类 3 中，大多数是初治儿童。聚类 1 中的免疫激活水平较低，聚类 3 中的免疫激活水平降低，聚类 2 中的免疫激活水平持续存在。各组血液微生物 DNA 水平均为阴性或极低，除肠杆菌科细菌外，各组间无差异（聚类 1 中水平较高；P<0.0001）。
结论
免疫激活随着 ART 的使用而减少，标志物聚类表明根据 HIV 和 ART 状态存在不同的激活模式。无论 HIV 状态、ART 状态和免疫激活状态如何，血液中细菌 DNA 的水平都较低。在这种情况下，微生物易位并未驱动免疫激活。
临床试验注册
ISRCTN69078957。
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