HIV Neurobehavioral Research Center (HNRC), University of California, San Diego, La Jolla, California 92093-0603, USA.
J Neurovirol. 2009 Sep;15(5-6):360-70. doi: 10.3109/13550280903131915.
The objective of this study was to examine the spectrum of human immunodeficiency virus (HIV) brain pathology and its clinical correlates in the antiretroviral era. We carried out a cross-sectional survey, analyzing prospective clinical and neuropathological data collected by the National NeuroAIDS Tissue Consortium (NNTC), comprising 589 brain samples from individuals with advanced HIV disease collected from 1999 onwards. We assessed gender, ethnicity/race, mode of transmission, age, year of death, nadir CD4, plasma viral load, last antiretroviral regimen, presence of parenchymal HIV brain pathology, HIV-associated neurocognitive disorder, and major depressive disorder. We compared cohort demographic variables with Centers for Disease Control and Prevention US HIV/AIDS statistics and examined associations of parenchymal HIV brain pathology with demographic, clinical, and HIV disease factors. With regard to Centers for Disease Control and Prevention US data, the NNTC was similar in age distribution, but had fewer females and African Americans and more Hispanics and men who have sex with men. Only 22% of the brains examined were neuropathologically normal. Opportunistic infections occurred in 1% to 5% of the cohort. Parenchymal HIV brain pathology was observed in 17.5% of the cohort and was associated with nadir CD4 and plasma viral load. Brains without parenchymal HIV brain pathology often had other noninfectious findings or minimal nondiagnostic abnormalities that were associated with HIV-associated neurocognitive disorder. Clinically, 60% of the cohort reported a lifetime episode of major depressive disorder and 88% had a HIV-associated neurocognitive disorder. No pathological finding correlated with major depressive disorder. Both antiretroviral treatment regimen and elevated plasma HIV viral load were associated with presence of parenchymal HIV brain pathology; however, multivariate analyses suggest a stronger association with plasma viral load. The frequency of HIV brain pathology was lower than previous pre-antiretroviral reports, and was predicted by lower nadir CD4 and higher plasma viral load. Noninfectious pathologies and minimal changes correlated with HIV-associated neurocognitive disorder, suggesting a shift in pathogenesis from florid HIV replication to other, diverse mechanisms.
本研究旨在探讨在抗逆转录病毒时代人类免疫缺陷病毒 (HIV) 脑病理学的范围及其与临床的相关性。我们进行了一项横断面调查，分析了国家神经艾滋病组织联盟 (NNTC) 前瞻性收集的临床和神经病理学数据，该联盟包括自 1999 年以来从患有晚期 HIV 疾病的个体中收集的 589 个脑样本。我们评估了性别、种族/民族、传播模式、年龄、死亡年份、CD4 细胞最低点、血浆病毒载量、最后一次抗逆转录病毒治疗方案、实质 HIV 脑病理学、HIV 相关认知障碍和重度抑郁症的存在情况。我们将队列的人口统计学变量与美国疾病控制与预防中心 (CDC) 的 HIV/AIDS 统计数据进行了比较，并检查了实质 HIV 脑病理学与人口统计学、临床和 HIV 疾病因素的相关性。就美国 CDC 数据而言，NNTC 在年龄分布上相似，但女性和非裔美国人较少，西班牙裔和男男性行为者较多。只有 22%的大脑检查结果为神经病理学正常。机会性感染在队列中占 1%至 5%。实质 HIV 脑病理学在队列中占 17.5%，与 CD4 细胞最低点和血浆病毒载量有关。没有实质 HIV 脑病理学的大脑通常存在其他非传染性发现或最小的非诊断性异常，这些发现与 HIV 相关的认知障碍有关。临床上，60%的队列报告有终生的重度抑郁症发作，88%的人有 HIV 相关的认知障碍。没有病理发现与重度抑郁症相关。抗逆转录病毒治疗方案和血浆 HIV 病毒载量升高均与实质 HIV 脑病理学的存在有关；然而，多变量分析表明与血浆病毒载量的关联更强。HIV 脑病理学的频率低于以前的抗逆转录病毒报告，并且与 CD4 细胞最低点较低和血浆病毒载量较高有关。非传染性病变和微小变化与 HIV 相关的认知障碍相关，这表明发病机制从明显的 HIV 复制转变为其他不同的机制。
