NEUROPROTECTION WITH SELENIUM THERAPY IN HIV+ IDUS

艾滋病毒疾病的主要神经精神并发症是认知运动障碍，据报告，HIV-1血清反应阳性的吸毒者患艾滋病毒相关痴呆症的风险更高，神经功能障碍进展更快。可导致神经元变性的氧化应激在HIV-1疾病中增加，并且似乎因滥用药物而增强。这项辅助研究的主要目的是确定补充硒（一种保护细胞免受氧化损伤所需的生物抗氧化剂）是否可以提供神经保护并帮助维持HIV-1血清阳性慢性吸毒者的认知功能。补充硒已被证明可以改善艾滋病毒/艾滋病患者的氧化防御系统，并抑制神经系统患者的精神恶化。我们对HIV-1感染的吸毒者的初步调查表明，低水平的硒与精神表现下降有关，短期补充硒对改善精神功能和情绪状态有很大的潜力。这些数据表明，硒的管理可能是一种有效的策略，以防止认知能力的丧失。我们建议扩展我们目前由NIDA资助的临床试验“硒疗法减缓HIV+ IDUs疾病进展”，以比较硒或安慰剂对神经心理功能的影响。在补充之前，将在母研究的基线访视时招募已确诊的HIV-1感染的吸毒者（n=120），并每6个月施用一次心理社会和认知成套疗法，持续30个月。母研究将在与认知和社会心理成套检查相同的访视时收集药物使用、营养、免疫、氧化应激和健康状况数据，并提供给拟定项目。这两项研究之间没有直接的科学重叠。拟议的合作和具有成本效益的研究提供了一个独特的机会，以进一步了解神经心理功能的HIV-1血清阳性的男性和女性谁滥用药物，以及提供必要的重要信息，为管理认知障碍的HIV-1疾病。

The major neuropsychiatric complication in HIV-disease is cognitive-motor impairment, with HIV-1 seropositive drug users reported to be at higher risk for the development of HIV-associated dementia and more rapid progression in neurologic disability. Oxidative stress, which can lead to neuronal degeneration, is increased in HIV-1 disease and appears to be potentiated by drugs of abuse. The primary objective of this ancillary study is to determine whether supplementation with selenium, a biologic antioxidant that is required for protecting cells from oxidative damage, can provide neuroprotection and help maintain cognitive function in HIV-l seropositive chronic drug users. Supplementation with selenium has been shown to improve oxidative defense systems in HIV/AIDS patients, and inhibit mental deterioration in neurologic patients. Our preliminary investigations in HIV- l infected drug users indicate that low levels of selenium are associated with decreased mental performance, and that short-term selenium supplementation results in a strong potential for improvement in mental function and mood state. These data suggest that administration of selenium may be an effective strategy to prevent loss of cognitive ability. We propose to extend our currently NIDA-funded, clinical trial, "Selenium Therapy to Slow Disease Progression in HIV+ IDUs", to compare the effects of selenium or placebo on neuropsychological function. Consented HIV-l infected drug users (n=120) will be enrolled at the baseline visit of the parent study, prior to supplementation, and administered a psychosocial and cognitive battery every 6 months for 30 months. Drug use, nutritional, immunologic, oxidative stress, and health status data will be collected by the parent study at the same visit as the cognitive and psychosocial battery, and made available for the proposed project. There is no direct scientific overlap between the two studies. The proposed collaborative and cost-effective research provides a unique opportunity to further our understanding of neuropsychological function in HIV-l seropositive men and women who abuse drugs, as well as provide important information necessary for the management of cognitive impairment in HIV-1 disease.