MRC/UCT Medical Imaging Research Unit, Division of Biomedical Engineering, Department of Human Biology, Faculty of Health Sciences, University of Cape Town, Cape Town, South Africa.
Family Clinical Research Unit, Department of Paediatrics & Child Health, Tygerberg Children's Hospital and Faculty of Health Sciences, Stellenbosch University, Cape Town, South Africa.
Metab Brain Dis. 2018 Apr;33(2):523-535. doi: 10.1007/s11011-017-0162-6. Epub 2017 Dec 5.
Even with the increased roll out of combination antiretroviral therapy (cART), paediatric HIV infection is associated with neurodevelopmental delays and neurocognitive deficits that may be accompanied by alterations in brain structure. Few neuroimaging studies have been done in children initiating ART before 2 years of age, and even fewer in children within the critical stage of brain development between 5 and 11 years. We hypothesized that early ART would limit HIV-related brain morphometric deficits at age 7. Study participants were 7-year old HIV-infected (HIV+) children from the Children with HIV Early Antiretroviral Therapy (CHER) trial whose viral loads were supressed at a young age, and age-matched uninfected controls. We used structural magnetic resonance imaging (MRI) and FreeSurfer ( http://www.freesurfer.net/ ) software to investigate effects of HIV and age at ART initiation on cortical thickness, gyrification and regional brain volumes. HIV+ children showed reduced gyrification compared to controls in bilateral medial parietal regions, as well as reduced volumes of the right putamen, left hippocampus, and global white and gray matter and thicker cortex in small lateral occipital region. Earlier ART initiation was associated with lower gyrification and thicker cortex in medial frontal regions. Although early ART appears to preserve cortical thickness and volumes of certain brain structures, HIV infection is nevertheless associated with reduced gyrification in the parietal cortex, and lower putamen and hippocampus volumes. Our results indicate that in early childhood gyrification is more sensitive than cortical thickness to timing of ART initiation. Future work will clarify the implications of these morphometric effects for neuropsychological function.
即使联合抗逆转录病毒疗法（cART）的应用不断增加，儿科 HIV 感染仍与神经发育迟缓以及神经认知缺陷相关，这些缺陷可能伴随着大脑结构的改变。在 2 岁以下开始接受 ART 的儿童中，很少有神经影像学研究，而在 5 至 11 岁大脑发育关键阶段的儿童中，更是少之又少。我们假设早期 ART 将限制 7 岁时与 HIV 相关的大脑形态计量学缺陷。研究参与者为来自儿童 HIV 早期抗逆转录病毒治疗（CHER）试验的 7 岁感染 HIV（HIV+）儿童，他们的病毒载量在很小的时候就被抑制，并且与年龄匹配的未感染对照者。我们使用结构磁共振成像（MRI）和 FreeSurfer（http://www.freesurfer.net/）软件来研究 HIV 和 ART 开始年龄对皮质厚度、脑回和区域脑体积的影响。与对照组相比，HIV+儿童双侧内侧顶叶区域的脑回减少，右侧壳核、左侧海马体以及全球白质和灰质体积减少，而小的外侧枕叶区域的皮质增厚。ART 开始得越早，内侧额区的脑回越不规则，皮质越厚。尽管早期 ART 似乎可以维持皮质厚度和某些脑结构的体积，但 HIV 感染仍与顶叶皮层的脑回减少以及壳核和海马体体积减小相关。我们的结果表明，在幼儿期，脑回的不规则程度比皮质厚度对 ART 开始时间更为敏感。未来的研究将阐明这些形态计量学效应对神经心理学功能的影响。
