The effects of HIV and combination antiretroviral therapy on white matter integrity.
The effects of HIV and combination antiretroviral therapy on white matter integrity.
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DOI：
10.1097/qad.0b013e3283550bec
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发表时间：
2012-07-31
期刊：
影响因子：
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通讯作者：
Ances BM
中科院分区：
文献类型：
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作者：
Wright PW;Heaps JM;Shimony JS;Thomas JB;Ances BM
HIV优先影响大脑中的白色物质（WM）。虽然联合抗逆转录病毒疗法（cART）减少了大脑中的HIV病毒载量，但持续的炎症可能会持续存在。扩散张量成像（DTI）提供了一种非侵入性方法，以评估WM结构完整性的cART时代。我们使用DTI检查了HIV和cART对胼胝体（CC）和半卵圆中心（CSO）内WM完整性的影响。神经心理学测试和DTI扫描采集了一个由63名个体组成的横断面队列，这些个体被分为三组之一：21名HIV未感染（HIV-）对照组，21名HIV感染（HIV+）受试者未接受过cART（HIV+/cART-），21名HIV+受试者接受稳定的cART（HIV+/cART+）。获得了CC和CSO的颈动脉、压部和体部的DTI测量值（各向异性分数（FA）、平均扩散率（MD）、轴向扩散率（AD）、径向扩散率（RD））。HIV+/cART-个体（n=10）的一个子集也在接受稳定治疗前即刻和治疗后约6个月进行了纵向评估。使用ANOVA评估横截面组之间的差异，而配对t检验评估纵向变化。与HIV-对照组和HIV+/cART+个体相比，每个CC区域和CSO的HIV+/cART-参与者的MD、AD和RD显著较低。观察到的DTI参数降低可反映HIV+/cART-受试者WM中存在炎性细胞或细胞毒性水肿。HIV-对照组和HIV+/cART+受试者之间无显著差异。在一些HIV+受试者中，启动cART导致CC和CSO地区MD、RD和AD显著增加，但未导致FA显著增加。在开始cART后观察到的WM中DTI参数的变化可以反映神经炎症的减少。未来的DTI研究可能有助于评估具有更高脑渗透性的cART方案的疗效。
HIV preferentially affects white matter (WM) in the brain. While combination antiretroviral therapy (cART) reduces HIV viral load within the brain, continued inflammation can persist. Diffusion tensor imaging (DTI) provides a non-invasive method to assess WM structural integrity in the cART era. We examined the impact of HIV and cART on WM integrity within the corpus callosum (CC) and centrum semiovale (CSO) using DTI. Neuropsychological testing and DTI scans were acquired for a cross-sectional cohort consisting of 63 individuals that were divided into one of three groups: 21 HIV-uninfected (HIV-) controls, 21 HIV-infected (HIV+) subjects naïve to cART (HIV+/cART-), and 21 HIV+ subjects receiving stable cART (HIV+/cART+). DTI measures (fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (AD), radial diffusivity (RD)) were obtained for the genu, splenium, and body of the CC as well as the CSO. A subset of the HIV+/cART- individuals (n=10) were also longitudinally assessed immediately before and approximately 6 months after receiving stable therapy. Differences among the cross-sectional groups were assessed using an ANOVA while paired t-tests evaluated longitudinal changes. The HIV+/cART- participants had significantly lower MD, AD, and RD for each CC region and the CSO compared to HIV- controls and HIV+/cART+ individuals. Observed decreases in DTI parameters could reflect the presence of inflammatory cells or cytotoxic edema in the WM of HIV+/cART- subjects. No significant difference existed between HIV- controls and HIV+/cART+ subjects. In some HIV+ subjects, initiation of cART led to significant increases in MD, RD, and AD but not FA in the CC and CSO regions. Observed changes in DTI parameters in the WM after initiating cART could reflect reduced neuro-inflammation. Future DTI studies may be useful in evaluating the efficacy of cART regimens with higher brain penetration.