NeuroAIDS in Cameroon: Molecular determinants

描述（由申请人提供）：hiv相关的神经认知障碍（HNCD）在感染患者中很常见，从神经认知缺陷到痴呆。这些并发症在抗逆转录病毒治疗前和治疗后都有详细的记录。然而，这些研究绝大多数是在发达国家进行的，涉及的患者感染了HIV-1的主要B亚型。目前4030万艾滋病毒/艾滋病感染者中有26人生活在撒哈拉以南非洲，该地区83%的艾滋病患者无法获得抗逆转录病毒治疗。目前发表的关于非洲神经艾滋病的研究大多是病例报告，有必要进行有组织的、控制良好的研究，以评估非洲感染者中高传染性疾病的发病率和流行程度。乌干达最近的一项研究表明，与其他分支相比，感染HIV-1亚型D增加了艾滋病迅速死亡的可能性。喀麦隆的艾滋病毒流行病是独特的，其特点是遗传多样性非常广泛；喀麦隆已记录了多种艾滋病毒毒株的感染。这种遗传多样性对神经aids的易感性和发展的影响尚不清楚。此外，其他HIV基因型在神经艾滋病的发病率、流行率或进展率或全身性HIV表现方面是否存在差异尚不清楚。我们假设HIV基因型可以影响患者对神经艾滋病的易感性和疾病进展。首席研究员发起了一项与雅温得大学的合作，以确定喀麦隆神经艾滋病的流行病学特征及其分子决定因素。这项试点研究的目标是在喀麦隆调整、规范和实施神经医学和神经行为测试程序，证明收集样本并将其转移到UNMC进行分子测试的可行性：目标1：培训喀麦隆研究人员进行神经医学和神经行为测试；在喀麦隆对国家精神卫生研究所艾滋病工作组推荐的神经心理学测试组的一个子集进行试点测试；HIV阳性患者的神经医学评价；目标3：确定将样本从喀麦隆转移到内布拉斯加州大学医学中心的可行性，并通过对一小组艾滋病毒阳性患者（有和没有艾滋病毒感染）样本中的艾滋病毒包膜进行测序，开展分子研究。研究的这一阶段将确定确定和招募参与者，在喀麦隆实施NP测试仪器和获取样本的可行性。它将为喀麦隆人群的神经认知测试提供规范性数据，并为我们未来的R01奠定基础，R01的目标是对喀麦隆神经艾滋病的流行病学和分子决定因素进行更明确的研究。与项目相关的神经系统并发症在艾滋病毒感染者中很常见，有必要在受艾滋病毒/艾滋病影响最严重的撒哈拉以南非洲地区研究这些并发症。这项提议调查是否感染HIV分离物具有特定的遗传特征，使患者更容易患神经认知障碍。它将提供关于喀麦隆神经艾滋病流行病学的知识，并为喀麦隆未来的神经艾滋病研究和治疗试验建设能力。

DESCRIPTION (provided by applicant): HIV-related neurocognitive disorders (HNCD) are common in infected patients, ranging from neurocognitive deficits to dementia. These complications have been well documented, both in the pre- and post-antiretroviral therapy (ART) periods. However, the vast majority of these studies were done in developed countries and involved patients infected with the predominant B subtype of HIV-1. Twenty six of the 40.3 million people currently living with HIV/AIDS are in sub-Saharan Africa and 83% of AIDS patients from this region do not have access to ART. Current published studies on neuroAIDS in Africa are mostly case reports and there is a need for structured, well-controlled studies that assess the incidence and prevalence of HNCD among infected people in Africa. A recent study in Uganda suggests that infection with HIV-1 subtype D compared to other clades increases the likelihood of rapid death from AIDS. The HIV epidemic in Cameroon is unique and is characterized by a very broad genetic diversity; infection with multiple HIV strains has been documented in Cameroon. The effect of this genetic diversity on the susceptibility and development of neuroAIDS is not known. Furthermore, whether other HIV genotypes differ in incidence, prevalence, or rate of progression of neuroAIDS or in systemic HIV manifestations is unclear. We hypothesize that HIV genotype can influence the patient's susceptibility to neuroAIDS and disease progression. The principal investigator has initiated a collaboration with the University of Yaound¿ to characterize the epidemiology of neuroAIDS in Cameroon and its molecular determinants The objective of this pilot study is to adapt, normalize and implement in Cameroon neuromedical and neurobehavioral test procedures, demonstrate the feasibility of collecting and transferring samples to UNMC for molecular testing: Aim 1: Train Cameroon investigators in neuromedical and neurobehavioral testing, Aim 2: Pilot test in Cameroon of a subset of a National Institute of Mental Health AIDS workgroup-recommended neuropsychological test battery; and neuromedical evaluation of HIV+ patients; Aim 3: Establish the feasibility of transferring samples from Cameroon to the University of Nebraska Medical Center and set up molecular studies by sequencing the HIV envelope in a small group of samples from HIV+ patients with and without HNCD. This phase of the study will determine the feasibility of identifying and recruiting participants, implementing NP test instruments in Cameroon and getting samples. It will provide normative data for neurocognitive testing among Cameroon population and lay the ground work for our future R01 which objective will be to perform a more definitive study of the epidemiology and molecular determinants of neuroAIDS in Cameroon. PROJECT RELEVANCE Neurological complications are common among HIV-infected individuals and there is a need to study theses complications in sub-Saharan Africa, the region worst affected by the HIV/AIDS pandemic. This proposal investigates whether infections with HIV isolates that have a particular genetic characteristic makes patients more susceptible to neurocognitive disorders. It will provide knowledge on the epidemiology of neuroAIDS in Cameroon and build the capacity for future neuroAIDS research and therapeutic testing in Cameroon.