Spudich Serena S
Yale University, New Haven, CT, USA.
Top Antivir Med. 2014 May;22(2):594-601.
A shift in focus in the field of neuroHIV was clearly manifest at the 2014 Conference on Retroviruses and Opportunistic Infections (CROI), where a major emphasis was on the milder forms of neurologic morbidity, including cognitive impairment, seen in well-treated patients. Mechanisms of this persistent abnormality were investigated, including extensive analysis of the prevalence and associations of persistent HIV detection in cerebrospinal fluid (CSF) and characterization of persistent CNS immune activation. Another key emphasis was the early establishment of HIV replication and inflammation within the central nervous system (CNS) and the potentially salutary effect of very early HIV diagnosis and treatment in protecting the CNS from HIV-related injury. Mitochondrial function was identified as a potential mediator of a number of aspects of HIV-associated CNS dysfunction, including neurotoxicity associated with efavirenz, host genetic determinants of HIV-associated neurocognitive disorders (HAND), associations with direct measures of mitochondria in CSF, and metabolomic screening of CSF in HIV-infected subjects and those with HAND. Many studies employed laboratory rather than neuropsychologic end points, with a major focus on CSF biomarkers. Overall, neuroHIV presentations at CROI 2014 provided new insights into pathogenesis and treatment of the CNS, raising new challenges for researchers and practitioners aiming to optimize the status of the brain in people living with HIV infection.
神经艾滋病领域的重点转移在2014年逆转录病毒与机会性感染会议(CROI)上清晰显现,该会议主要强调了在接受良好治疗的患者中出现的较轻微神经病变形式,包括认知障碍。对这种持续性异常的机制进行了研究,包括对脑脊液(CSF)中持续检测到HIV的患病率和相关性进行广泛分析,以及对持续性中枢神经系统免疫激活进行特征描述。另一个关键重点是HIV在中枢神经系统(CNS)内早期复制和炎症的建立,以及极早期HIV诊断和治疗在保护中枢神经系统免受HIV相关损伤方面可能产生的有益效果。线粒体功能被确定为HIV相关中枢神经系统功能障碍多个方面的潜在介质,包括与依非韦伦相关的神经毒性、HIV相关神经认知障碍(HAND)的宿主基因决定因素、与脑脊液中线粒体直接测量指标的相关性,以及对HIV感染受试者和HAND患者脑脊液的代谢组学筛查。许多研究采用实验室而非神经心理学终点,主要关注脑脊液生物标志物。总体而言,2014年CROI会议上的神经艾滋病报告为中枢神经系统的发病机制和治疗提供了新见解,给旨在优化HIV感染者脑部状况的研究人员和从业者带来了新挑战。