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.
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