Letendre Scott, McCutchan J Allen, Ellis Ronald J
Department of Medicine, Division of Infectious Diseases, University of California San Diego, San Diego, CA, USA.
Top HIV Med. 2008 Apr-May;16(1):15-22.
New data were presented at the 15th Conference on Retroviruses and Opportunistic Infections that further support the importance of considering the neuroeffectiveness of antiretroviral drugs when designing treatment regimens. Two studies linked antiretroviral therapy that had estimates of better neuroeffectiveness with better global neuropsychologic outcomes in life. A third study linked estimates of better antiretroviral therapy neuroeffectiveness, particularly nonnucleoside analogue reverse transcriptase inhibitors, with a lower prevalence of HIV-associated brain pathology at death. Additional findings presented at the conference focused on the correlates of HIV-associated neurocognitive disorders (HAND) and peripheral neuropathy. Supporting the concept that viral factors influence the pathogenesis of HAND, high frequencies of HAND were identified in people infected with HIV subtype D and in people infected with subtype B and having brain-specific mutations in V3 of gp160. Supporting the importance of host correlates of HAND, important data from a macaque study identified a strong link between a major histocompatibility complex class I allele, Mane-A*10, and simian immunodeficiency virus encephalitis. Supporting the importance of comorbidities in determining risk for HAND, high levels of lipopolysaccharide in blood, likely derived from the HIV-injured intestine and bacterial translocation, were linked to HAND. Coinfections with JC virus or Treponema pallidum were topics of other presentations, identifying a prognostic marker for PML (better CD8+ cytotoxic T-lymphocyte responses were associated with survival) and a diagnostic one for neurosyphilis (CXCL13 levels in CSF).
在第15届逆转录病毒与机会性感染会议上公布的新数据进一步支持了在设计治疗方案时考虑抗逆转录病毒药物神经有效性的重要性。两项研究将估计神经有效性较好的抗逆转录病毒疗法与生活中更好的整体神经心理结果联系起来。第三项研究将估计较好的抗逆转录病毒疗法神经有效性,特别是非核苷类逆转录酶抑制剂,与死亡时HIV相关脑病变的较低患病率联系起来。会议上展示的其他研究结果聚焦于HIV相关神经认知障碍(HAND)和周围神经病变的相关因素。支持病毒因素影响HAND发病机制这一概念的是,在感染HIV D亚型的人群以及感染B亚型且gp160的V3区有脑特异性突变的人群中发现了高频率的HAND。支持HAND宿主相关因素重要性的是,一项猕猴研究的重要数据确定了主要组织相容性复合体I类等位基因Mane - A*10与猴免疫缺陷病毒脑炎之间的紧密联系。支持合并症在确定HAND风险中重要性的是,血液中高水平的脂多糖(可能源自HIV损伤的肠道和细菌易位)与HAND有关。与JC病毒或梅毒螺旋体的合并感染是其他报告的主题,确定了进行性多灶性白质脑病的一个预后标志物(较好的CD8 + 细胞毒性T淋巴细胞反应与生存相关)以及神经梅毒的一个诊断标志物(脑脊液中的CXCL13水平)。