NeuroAIDS in Cameroon: Molecular determinants

描述（由申请人提供）：HIV相关神经认知障碍（HNCD）在感染患者中很常见，范围从神经认知缺陷到痴呆。这些并发症在抗逆转录病毒治疗（ART）前后都有很好的记录。然而，这些研究中的绝大多数是在发达国家进行的，涉及感染HIV-1主要B亚型的患者。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。目前发表的非洲神经艾滋病研究大多是病例报告，需要进行结构化、对照良好的研究，评估非洲感染者中HNCD的发病率和患病率。最近在乌干达进行的一项研究表明，与其他分支相比，感染HIV-1 D亚型增加了艾滋病快速死亡的可能性。艾滋病毒在喀麦隆的流行是独特的，其特点是遗传多样性非常广泛;在喀麦隆有多种艾滋病毒毒株感染的记录。这种遗传多样性对神经艾滋病的易感性和发展的影响尚不清楚。此外，其他HIV基因型是否在神经艾滋病的发病率、流行率或进展速度或系统性HIV表现方面存在差异尚不清楚。我们假设HIV基因型可以影响患者对neuroAIDS的易感性和疾病进展。主要研究员已开始与雅温得大学合作，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。这项试点研究的目的是在喀麦隆调整、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联合国监测委员会进行分子测试的可行性：对喀麦隆调查人员进行神经医学和神经行为测试培训，目标2：在喀麦隆对国家精神卫生研究所艾滋病工作组建议的神经心理成套测试的一部分进行试点测试;对艾滋病毒阳性患者进行神经医学评估;目标3：确定将样本从喀麦隆转移到内布拉斯加大学医学中心的可行性，并通过对来自有和没有HNCD的HIV+患者的一小组样本中的HIV包膜进行测序来进行分子研究。这一阶段的研究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R 01奠定基础，其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。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/艾滋病流行影响最严重的撒哈拉以南非洲地区研究这些并发症。这项提案调查了具有特定遗传特征的HIV分离株感染是否会使患者更容易患上神经认知障碍。它将提供喀麦隆神经艾滋病流行病学知识，并建设喀麦隆今后神经艾滋病研究和治疗试验的能力。

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.