Larger Subcortical Gray Matter Structures and Smaller Corpora Callosa at Age 5 Years in HIV Infected Children on Early ART.
Larger Subcortical Gray Matter Structures and Smaller Corpora Callosa at Age 5 Years in HIV Infected Children on Early ART.
复制标题
DOI：
10.3389/fnana.2017.00095
复制
发表时间：
2017
影响因子：
2.9
通讯作者：
Meintjes EM
中科院分区：
文献类型：
--
作者：
Randall SR;Warton CMR;Holmes MJ;Cotton MF;Laughton B;van der Kouwe AJW;Meintjes EM
撒哈拉以南非洲地区是90%感染艾滋病毒（HIV +）儿童的家园。自从抗逆转录病毒疗法（ART）出现以来，艾滋病毒/艾滋病已转变为一种慢性疾病，其中中枢神经系统（CNS）的损伤可能持续存在。尽管大多数指南建议早期进行抗逆转录病毒治疗以减少中枢神经系统的病毒储存库，但在生命最初几年的快速发育阶段，大脑可能更容易受到抗逆转录病毒治疗潜在的神经毒性影响。在此，我们通过手动描绘磁共振图像，研究了在18个月龄前接受早期抗逆转录病毒治疗的5岁HIV +儿童与未感染儿童之间皮质下体积的差异。参与者包括来自艾滋病毒儿童早期抗逆转录病毒（CHER）试验的61名科萨儿童（43名HIV + / 18名未感染，平均年龄 = 5.4 ± 0.3岁，27名男孩）；27名儿童在12周龄前开始抗逆转录病毒治疗（ART - 在12周前），16名在12周后开始（ART - 在12周后）。结构图像是在开普敦的一台3T Allegra磁共振成像仪上获取的，并使用MultiTracer手动描绘。对尾状核、伏隔核（NA）、壳核（Pu）、苍白球（GP）和胼胝体（CC）的体积组间差异（HIV +与未感染；ART - 在12周前与ART - 在12周后）进行了检查，以及在感染儿童中结构体积与抗逆转录病毒治疗开始时的年龄以及作为免疫健康指标的CD4/CD8之间的关联。HIV +儿童双侧伏隔核和壳核体积以及左侧苍白球体积显著大于对照组，而胼胝体较小。与对照组相比，两个治疗组的双侧壳核均较大，而左侧苍白球和双侧伏隔核仅在ART - 在12周后开始治疗的儿童中增大。与对照组相比，两个治疗组的胼胝体均较小，且ART - 在12周后开始治疗组的胼胝体比ART - 在12周前开始治疗组更小。在感染儿童中，延迟开始抗逆转录病毒治疗与较大的壳核体积相关，在控制性别和治疗中断持续时间后，这种影响仍然显著（左侧β = 0.447，p = 0.005；右侧β = 0.325，p = 0.051），较低的CD4/CD8与较大的尾状核相关（在控制性别后，左侧β = -0.471，p = 0.002；右侧β = -0.440，p = 0.003）。在12周后开始抗逆转录病毒治疗的儿童中体积差异更大。结果表明，尽管进行了早期抗逆转录病毒治疗和病毒载量抑制，但损伤仍在持续；然而，更早的治疗具有神经保护作用。
Sub-Saharan Africa is home to 90% of HIV infected (HIV+) children. Since the advent of antiretroviral therapy (ART), HIV/AIDS has transitioned to a chronic condition where central nervous system (CNS) damage may be ongoing. Although, most guidelines recommend early ART to reduce CNS viral reservoirs, the brain may be more vulnerable to potential neurotoxic effects of ART during the rapid development phase in the first years of life. Here we investigate differences in subcortical volumes between 5-year-old HIV+ children who received early ART (before age 18 months) and uninfected children using manual tracing of Magnetic Resonance Images. Participants included 61 Xhosa children (43 HIV+/18 uninfected, mean age = 5.4 ± 0.3 years, 25 male) from the children with HIV early antiretroviral (CHER) trial; 27 children initiated ART before 12 weeks of age (ART-Before12Wks) and 16 after 12 weeks (ART-After12Wks). Structural images were acquired on a 3T Allegra MRI in Cape Town and manually traced using MultiTracer. Volumetric group differences (HIV+ vs. uninfected; ART-Before12Wks vs. ART-After12Wks) were examined for the caudate, nucleus accumbens (NA), putamen (Pu), globus pallidus (GP), and corpus callosum (CC), as well as associations within infected children of structure volumes with age at ART initiation and CD4/CD8 as a proxy for immune health. HIV+ children had significantly larger NA and Pu volumes bilaterally and left GP volumes than controls, whilst CC was smaller. Bilateral Pu was larger in both treatment groups compared to controls, while left GP and bilateral NA were enlarged only in ART-After12Wks children. CC was smaller in both treatment groups compared to controls, and smaller in ART-After12Wks compared to ART-Before12Wks. Within infected children, delayed ART initiation was associated with larger Pu volumes, effects that remained significant when controlling for sex and duration of treatment interruption (left β = 0.447, p = 0.005; right β = 0.325, p = 0.051), and lower CD4/CD8 with larger caudates controlling for sex (left β = −0.471, p = 0.002; right β = −0.440, p = 0.003). Volumetric differences were greater in children who initiated ART after 12 weeks. Results suggest damage is ongoing despite early ART and viral load suppression; however, earlier treatment is neuroprotective.
登录
查看更多内容
影响因子：
5.7
作者：
Dewey, Jeffrey;Hana, George;Russell, Troy;Price, Jared;McCaffrey, Daniel;Harezlak, Jaroslaw;Sem, Ekta;Anyanwu, Joy C.;Guttmann, Charles R.;Navia, Bradford;Cohen, Ronald;Tate, David F.
通讯作者：
Tate, David F.
影响因子：
3.2
作者：
Becker, James T.;Sanders, Joanne;Madsen, Sarah K.;Ragin, Ann;Kingsley, Lawrence;Maruca, Victoria;Cohen, Bruce;Goodkin, Karl;Martin, Eileen;Miller, Eric N.;Sacktor, Ned;Alger, Jeffery R.;Barker, Peter B.;Saharan, Priyanka;Carmichael, Owen T.;Thompson, Paul M.
通讯作者：
Thompson, Paul M.
影响因子：
3.6
作者：
Ackermann, Christelle;Andronikou, Savvas;Cotton, Mark
通讯作者：
Cotton, Mark
影响因子：
3.2
作者：
Brouwers, P;Civitello, L;Sei, S
通讯作者：
Sei, S
影响因子：
1.9
作者：
Govender, Rajeshree;Eley, Brian;Wilmshurst, Jo M.
通讯作者：
Wilmshurst, Jo M.