High level HIV-1 DNA concentrations in brain tissues differentiate patients with post-HAART AIDS dementia complex or cardiovascular disease from those with AIDS.

Li Zhao, Derek C Galligan, Susanna L Lamers, Stephanie Yu, Lamia Shagrun, Marco Salemi, Michael S McGrath
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引用次数: 19

Abstract

Highly active antiretroviral treatment (HAART) has had a significant impact on survival of individuals with acquired immunodeficiency syndrome (AIDS); however, with the longer life-span of patients with AIDS, there is increasing prevalence of AIDS dementia complex (ADC) and other non-AIDS-defining illness, and cardiovascular diseases (CVD) are also common. The influence of these varied disease processes on HIV-1 DNA concentration in brain tissues has not been thoroughly assessed in the post-HAART era. The purpose of the current study is to clarify the impacts of ADC and other complications of HIV disease on the viral load in the brains in AIDS patients with post-HARRT. We examined autopsy specimens from the brains of thirteen patients who died from complications of AIDS with quantitative polymerase chain reaction (QPCR). All but one patient had received HAART prior to death since 1995. Two patients died with severe CVD, multiple cerebrovascular atherosclerosis (CVA) throughout the brain and five patients died with ADC. Six patients had no ADC/CVA. A QPCR was used to measure the presence of HIV-1 DNA in six brain tissues (meninges, frontal grey matter, frontal white matter, temporal subcortex, cerebellum and basal ganglia). In the post-HARRT era, for non-ADC/CVA patients, HIV-1 DNA concentration in brain tissues was statistically higher than that in patients with ADC. In a new finding, two patients who suffered from severe CVD, especially CVA, also had high concentrations of HIV-1 in brain compartments not showing ADC related changes. To our knowledge, this is the first report of a relationship between the CVA and HIV-1 viral burden in brain. The current observations suggest that HAART-resistant HIV reservoirs may survive within ADC lesions of the brain as well as the macrophage rich atherosclerosis, which needs to be confirmed by more AIDS cases with CVA.

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脑组织中高水平的HIV-1 DNA浓度可将haart后艾滋病痴呆复合物或心血管疾病患者与艾滋病患者区分开来。
高效抗逆转录病毒治疗(HAART)对获得性免疫缺陷综合征(艾滋病)患者的生存产生了重大影响;然而,随着艾滋病患者寿命的延长,艾滋病痴呆复合物(ADC)和其他非艾滋病定义疾病的患病率也在增加,心血管疾病(CVD)也很常见。在haart后时代,这些不同的疾病过程对脑组织中HIV-1 DNA浓度的影响尚未得到彻底评估。本研究的目的是阐明ADC和其他HIV疾病并发症对hart后艾滋病患者大脑病毒载量的影响。我们用定量聚合酶链反应(QPCR)检查了13例死于艾滋病并发症的患者的大脑尸检标本。自1995年以来,除一名患者外,所有患者在死亡前都接受过HAART治疗。2例患者死于严重CVD、全脑多发性脑血管粥样硬化(CVA), 5例患者死于ADC。6例患者无ADC/CVA。采用QPCR检测6个脑组织(脑膜、额叶灰质、额叶白质、颞叶下皮层、小脑和基底神经节)中HIV-1 DNA的存在。在后hart时代,非ADC/CVA患者脑组织中HIV-1 DNA浓度高于ADC患者。在一项新发现中,两名患有严重CVD(尤其是CVA)的患者在脑区也有高浓度的HIV-1,但未表现出与ADC相关的变化。据我们所知,这是首次报道CVA与大脑中HIV-1病毒负荷之间的关系。目前的观察结果表明,抗haart的HIV病毒库可能在大脑ADC病变以及富含巨噬细胞的动脉粥样硬化中存活,这需要更多的CVA艾滋病病例来证实。
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