EAEC Infection in HIV-infected Patients in Haiti

肠聚集性大肠杆菌（EAEC）是一种新兴的慢性腹泻的患者感染 在资源有限的情况下，为艾滋病毒感染者提供服务。感染EAEC与以下因素有关： 儿童营养不良和体重减轻。在艾滋病毒感染者中，即使接受抗逆转录病毒治疗， 营养不良和体重减轻是死亡率的重要预测因素。确定有助于 艾滋病毒感染者的营养不良和体重减轻至关重要。EAEC可能会发挥作用，但目前 EAEC感染对接受ART治疗的HIV感染患者的影响尚不清楚， 管理战略。 我最近评估了Au Prince港一项病例对照研究中患者的粪便样本。第一 当时，EAEC是海地艾滋病腹泻患者中最常见的病原体。此外，本发明还提供了一种方法， EAEC与治疗第一个月的体重减轻有关。拟议的研究将仔细 研究开始ART治疗的HIV感染成人中的EAEC感染。 与腹泻患者相比，感染EAEC的患者的临床结局更差， 未感染EAEC和未腹泻的人。主要结局将是每项研究中的患者百分比 一个月时体重减轻的组，死亡率的一个重要预测因素。次要结局将包括 存活48周。此外，我将评估细菌和患者基因型是否与 结果。评价的因素将包括编码细菌毒力因子的基因的流行率， 细菌生物膜的产生，单核苷酸多态性（SNP）的流行， 患者对EAEC感染的易感性，以及患者肠道炎症标志物的产生。 在前三年的奖项，我将追求培训的细菌原因和宿主的评价 对肠道感染的反应以及在资源有限的情况下的临床试验设计和研究伦理。 主办方和共同主办方在这些领域拥有丰富的经验，并将指导本次培训。 与此同时，我将利用与海地同事建立的关系， 建议的研究。研究结果将确立EAEC感染对HIV感染者的影响 在一个资源有限的国家，并告知临床战略的发展，以管理它。

Enteroaggregative Escherichia coli (EAEC) is an emerging cause of chronic diarrhea in patients infected with human immunodeficiency virus (HIV) in resource-limited settings. Infection with EAEC is associated with malnutrition and weight loss in children. In HIV-infected patients, even with antiretroviral therapy (ART), malnutrition and weight loss are important predictors of mortality. Establishing factors that contribute to malnutrition and weight loss in HIV-infected patients is essential. EAEC may play a role, but currently the impacts of EAEC infection on HIV-infected patients treated with ART are not clear nor are there established management strategies. I recently evaluated stool samples from patients in a case-control study in Port au Prince. For the first time, EAEC was the most commonly identified pathogen in Haitian AIDS patients with diarrhea. In addition, EAEC was associated with weight loss in the first month of therapy. The proposed study will carefully examine EAEC infection in HIV-infected adults initiating ART. I hypothesize that patients with diarrhea who are infected with EAEC will have worse clinical outcomes when compared to patients with diarrhea but uninfected with EAEC and to those without diarrhea. The primary outcome will be % of patients in each group with weight loss at one month, an important predictor of mortality. Secondary outcomes will include survival to 48 weeks. In addition, I will evaluate whether bacterial and patient genotypes correlate with outcomes. The factors evaluated will include the prevalence of genes encoding bacterial virulence factors, the production of bacterial biofilm, the prevalence of single nucleotide polymorphisms (SNP) that confer susceptibility to EAEC infection in the patients, and patient production of intestinal inflammatory markers. In the first three years of the award, I will pursue training in the evaluation of bacterial causes and host responses to enteric infections and in clinical trial design and research ethics in resource-limited settings. The sponsor and cosponsor have significant experience in these areas and will guide this training. Concurrently, I will build on established relationships with Haitian colleagues to set up and carry out the proposed study. The results of the study will establish the impact of EAEC infection on HIV-infected patients in a resource-limited country and inform the development of clinical strategies to manage it.