Miller Robert F, Isaacson Peter G, Hall-Craggs Margaret, Lucas Sebastian, Gray Françoise, Scaravilli Francesco, An Shu F
Department of Primary Care and Population Sciences, Centre for Sexually Transmitted Diseases, UCL, London, UK.
Acta Neuropathol. 2004 Jul;108(1):17-23. doi: 10.1007/s00401-004-0852-0. Epub 2004 Apr 14.
In HIV infected persons, highly active antiretroviral therapy (HAART) has reduced both the morbidity and incidence of several disorders. Its effects on direct HIV-induced damage to the CNS remain controversial. In addition, HAART may provoke an "immune reconstitution inflammatory syndrome" (IRIS). Herein we report two patients who, despite HAART, developed a diffuse encephalopathy. Their clinical, radiological and neuropathological features are described. Immunohistochemical and PCR analyses were used to detect HIV and to exclude other viruses in brain tissue. The unusual inflammatory reaction in the brain tissue was defined by immunohistochemistry. Both patients had advanced HIV disease with low CD4 counts and high HIV "viral loads" before starting HAART. In both, HAART induced an increase in CD4 count and a marked reduction in HIV viral load, which was accompanied, in patient one, by worsening of pre-existing, and, in patient two, by development of, acute encephalopathy. At post-mortem examination, the brain of patient one showed HIV encephalitis. In addition, the brains of both patients revealed HIV-DNA by PCR, diffuse microglial hyperplasia and massive and diffuse perivascular and intraparenchymal infiltration by CD8+/CD4- lymphocytes. We suggest that the rapid immune reconstitution induced by HAART in these two patients led to a redistribution of lymphocytes into peripheral blood. This was followed by recruitment of CD8+ lymphocytes into the brain, which resulted in the diffuse infiltration described. The appearances in patient two further suggest that HIV brain infection, even without encephalitis, is sufficient to trigger this response.
在HIV感染者中，高效抗逆转录病毒疗法（HAART）降低了多种疾病的发病率和发病几率。其对HIV直接导致的中枢神经系统损伤的影响仍存在争议。此外，HAART可能引发“免疫重建炎症综合征”（IRIS）。在此，我们报告两名患者，尽管接受了HAART治疗，但仍发生了弥漫性脑病。描述了他们的临床、放射学和神经病理学特征。采用免疫组织化学和PCR分析检测脑组织中的HIV并排除其他病毒。通过免疫组织化学确定脑组织中异常的炎症反应。两名患者在开始HAART治疗前均患有晚期HIV疾病，CD4计数低且HIV“病毒载量”高。在这两名患者中，HAART均导致CD4计数增加和HIV病毒载量显著降低，其中患者一在治疗过程中原有病情恶化，患者二则出现急性脑病。尸检时，患者一的大脑显示出HIV脑炎。此外，两名患者的大脑通过PCR均检测到HIV-DNA、弥漫性小胶质细胞增生以及CD8+/CD4-淋巴细胞大量弥漫性血管周围和实质内浸润。我们认为，HAART在这两名患者中诱导的快速免疫重建导致淋巴细胞重新分布到外周血中。随后CD8+淋巴细胞被募集到大脑中，导致了所述的弥漫性浸润。患者二的表现进一步表明，即使没有脑炎，HIV脑感染也足以引发这种反应。
