Weed Michael R, Steward David J
Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, MD 21224, USA.
Front Biosci. 2005 Jan 1;10:710-27. doi: 10.2741/1566.
Of the 40 million people living with HIV/AIDS worldwide in 2003, only 7% received highly active antiretroviral treatment (HAART). Without treatment, approximately half of AIDS patients will suffer from NeuroAIDS including neurological dysfunction, peripheral neuropathies, motor impairment, cognitive difficulties and frank dementia. HAART has reduced mortality from AIDS in the developed world, but CNS/neurological complications continue to be a leading cause of death or disability in AIDS patients on HAART. Despite years of use in developed countries, it is still not clear what the long-term impact of HAART will be on NeuroAIDS. The mechanisms of AIDS-related CNS pathology, in the presence or absence of HAART, are not completely understood. Infection with simian immunodeficiency virus (SIV) in macaques provides an excellent research model of AIDS, including AIDS-related CNS pathology and cognitive/behavioral impairments. A major goal of research with the SIV/macaque model has been to characterize behavioral and cognitive impairments in NeuroAIDS and elucidate the CNS pathology behind these impairments. Review of the studies assessing cognitive impairment in SIV infected macaques demonstrates the high concordance between neuropsychological impairment in human and simian AIDS. Consistent with results in human AIDS patients, SIV-infected monkeys tend to be impaired most often on tasks dependent upon intact frontal cortical and/or subcortical functioning. Building on the strengths of the SIV/macaque model of AIDS, directions for future research are discussed including further mechanistic studies of the neuropathology leading to cognitive impairment as well as assessment of the impact of antiretroviral therapy or drugs of abuse on NeuroAIDS.
2003年，全球有4000万人感染了艾滋病毒/艾滋病，其中只有7%的人接受了高效抗逆转录病毒治疗（HAART）。若不接受治疗，约一半的艾滋病患者会患上神经艾滋病，包括神经功能障碍、周围神经病变、运动障碍、认知困难和明显的痴呆症。HAART降低了发达国家艾滋病的死亡率，但中枢神经系统/神经并发症仍是接受HAART治疗的艾滋病患者死亡或致残的主要原因。尽管在发达国家已使用多年，但HAART对神经艾滋病的长期影响仍不明确。无论是否使用HAART，艾滋病相关中枢神经系统病理学的机制都尚未完全了解。猕猴感染猴免疫缺陷病毒（SIV）为艾滋病提供了一个极佳的研究模型，包括与艾滋病相关的中枢神经系统病理学以及认知/行为障碍。利用SIV/猕猴模型进行研究的一个主要目标是描述神经艾滋病中的行为和认知障碍，并阐明这些障碍背后的中枢神经系统病理学。对评估SIV感染猕猴认知障碍的研究进行综述表明，人类和猿类艾滋病中的神经心理障碍高度一致。与人类艾滋病患者的结果一致，感染SIV的猴子在依赖完整额叶皮质和/或皮质下功能的任务上最常出现障碍。基于SIV/猕猴艾滋病模型的优势，本文讨论了未来的研究方向，包括对导致认知障碍的神经病理学进行进一步的机制研究，以及评估抗逆转录病毒疗法或滥用药物对神经艾滋病的影响。
