International NeuroAIDS: Scientific and Methodological Research Challenges

描述（由申请人提供）：我们建议在五年内在美国举行一系列三次会议，以解决资源有限的国际神经艾滋病研究的科学机会和感知的方法障碍。神经艾滋病研究的焦点越来越多地取决于宿主-病毒相互作用和HAART影响的问题。虽然大多数艾滋病毒研究是在西方国家进行的，但艾滋病毒感染在撒哈拉以南非洲、东亚和南亚等资源有限的环境中最为普遍和最不受控制。在西方国家进行的研究结果主要来自于对HIV-1分支B感染和高加索人群的研究，因此可能无法推广到国际上的HIV分支和人群。此外，由于抗逆转录病毒疗法在国际上的应用越来越广泛，改善急性神经系统机会性感染的管理对短期生存至关重要，这反过来又使患者能够开始长期抗逆转录病毒疗法。在国际领域，三个关键的科学优先事项如下：机会性感染：在管理神经系统机会性感染方面仍然存在问题，这些问题是：a)发展中国家所特有的（例如脑型疟疾），b)在资源有限的环境中难以诊断和治疗（例如结核病和隐球菌脑膜炎、脑弓形虫病）。2. 抗病毒治疗：美国总统防治艾滋病紧急救援计划和联合国全球基金项目在资源有限的情况下大规模实施HAART治疗，出现了神经毒性、中枢神经系统渗透和中枢神经系统免疫重建综合症等问题，这些问题需要研究。3. 宿主和病毒遗传学：受影响人群和HIV（分支）的免疫遗传学和药物遗传学多样性可能改变神经艾滋病的表现。这些科学会议的第一次会议将审查发展中国家神经评估的方法问题。会议2将讨论ART的传播对神经艾滋病不断变化的影响，会议3将审查进展情况并提出国际神经艾滋病研究的未来议程。由NIMH P-30神经艾滋病中心主办的国际研究人员培训课程将与这些会议同时举行。通过提议的会议，我们的目标是：a)确定和纠正国际神经艾滋病研究的技术障碍，促进最先进的神经心理学研究技术的部署；b)检查发达国家和发展中国家在神经艾滋病的科学和临床问题上的差异；c)改善神经艾滋病的临床管理；d)检查抗逆转录病毒治疗对发展中国家神经艾滋病的影响。e)在资源有限的环境下为未来的神经艾滋病研究制定议程。我们将通过以下方式传播这些会议的摘要和讨论：向公众提供我们网站上的会议介绍，在其他科学会议上介绍会议摘要，以及以开放获取的印刷品和网络形式出版共识专著。

DESCRIPTION (provided by applicant): We propose a series of three meetings in the U.S. over five years to address scientific opportunities and perceived methodological hurdles to international neuroAIDS research in resource-limited settings. The focus of neuroAIDS research increasingly hinges on questions regarding host-virus interactions and impact of HAART. While the majority of HIV research has taken place in Western countries, HIV infection is most prevalent and least controlled in resource-limited settings such as sub-Saharan Africa, and East and South Asia. Findings from studies conducted in Western countries that derive mainly from work on HIV-1 Clade B infection and Caucasian populations therefore may not be generalizable to HIV clades and human populations internationally. Additionally, now that ART is increasingly available internationally, improved management of acute neurologic opportunistic infections is critical to short-term survival, which in turn enables patients to initiate long-term ART. In the international sphere, three critical scientific priorities are as follows: 1. Opportunistic Infections: Problems persist in the management of neurologic opportunistic infections that are: a) unique to developing countries (e.g. cerebral malaria), and b) difficult to diagnose and treat in resource-limited settings (e.g. tuberculosis and cryptococcal meningitis, cerebral toxoplasmosis). 2. Antiviral Therapy: Implementation of HAART on a massive scale by the U.S. PEPFAR and the U.N. Global Fund programs in resource-limited settings has presented problems of neurotoxicity, CNS penetration, and CNS immune-reconstitution syndromes that require study. 3. Host and Viral Genetics: The immunogenetic and pharmacogenetic diversity of affected human populations and of HIV (clades) may modify the manifestations of neuroAIDS. The first of these scientific meetings will examine methodological problems of neurological assessment in developing countries. Meeting 2 will address the changing impact on neuroAIDS of dissemination of ART, and meeting 3 will review progress and propose future agendas for international neuroAIDS research. Three training sessions for international investigators will be held in conjunction with these meetings, sponsored by the collaborating NIMH P-30 NeuroAIDS Centers. Through the proposed meetings, we aim to a) identify and correct technical barriers to international neuroAIDS research and facilitate deployment of state-of-the-art neuropsychological research technologies, b) examine differences in developed and developing countries in the scientific and clinical issues of neuroAIDS, c) improve clinical management of neuroAIDS, d) examine the impact of anti-retroviral therapy on neuroAIDS in developing countries, and e) set agendas for future neuroAIDS research in resource-limited settings. We will disseminate abstracts and discussions from these meetings via public access to meeting presentations on our web site, presentation of meeting summary at other scientific meetings, and publication of consensus monograph in open-access print and web-based forms.