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.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Mentored Patient-Oriented Research Career Development Award (K23)
Project #
5K23AI077339-05
Application #
8291384
Study Section
Acquired Immunodeficiency Syndrome Research Review Committee (AIDS)
Program Officer
Bacon, Melanie C
Project Start
2008-07-07
Project End
2014-06-30
Budget Start
2012-07-01
Budget End
2014-06-30
Support Year
5
Fiscal Year
2012
Total Cost
$128,817
Indirect Cost
$9,542
Name
University of Virginia
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
065391526
City
Charlottesville
State
VA
Country
United States
Zip Code
22904
Mitchell, Emma McKim; Steeves, Richard; Dillingham, Rebecca (2015) Cruise ships and bush medicine: globalization on the Atlantic Coast of Nicaragua and effects on the health of Creole women. Public Health Nurs 32:237-45
Ingersoll, Karen; Dillingham, Rebecca; Reynolds, George et al. (2014) Development of a personalized bidirectional text messaging tool for HIV adherence assessment and intervention among substance abusers. J Subst Abuse Treat 46:66-73
McManus, Kathleen A; Pinkerton, Relana; Dillingham, Rebecca (2014) Effects of recent Virginia AIDS Drug Assistance Program policy changes on diabetes and hyperlipidemia control in people living with HIV. SAGE Open Med 2:
Mellor, Jonathan; Abebe, Lydia; Ehdaie, Beeta et al. (2014) Modeling the sustainability of a ceramic water filter intervention. Water Res 49:286-99
Liu, Jie; Winstead-Derlega, Christopher; Houpt, Eric et al. (2014) Pre-earthquake non-epidemic Vibrio cholerae in Haiti. J Infect Dev Ctries 8:120-2
Bartelt, Luther A; Sevilleja, Jesus Emmanuel; Barrett, Leah J et al. (2013) High anti-Cryptosporidium parvum IgG seroprevalence in HIV-infected adults in Limpopo, South Africa. Am J Trop Med Hyg 89:531-4
Schafer, Katherine R; Gupta, Shruti; Dillingham, Rebecca (2013) HIV-infected men who have sex with men and histories of childhood sexual abuse: implications for health and prevention. J Assoc Nurses AIDS Care 24:288-98
Dillingham, Rebecca; Leger, Paul; Beauharnais, Carole-Anne et al. (2011) AIDS diarrhea and antiretroviral drug concentrations: a matched-pair cohort study in Port au Prince, Haiti. Am J Trop Med Hyg 84:878-82
Heckman, James; Samie, Amidou; Bessong, Pascal et al. (2010) Anaemia among clinically well under-fives attending a community health centre in Venda, Limpopo Province. S Afr Med J 100:445-8
Leger, Paul; Dillingham, Rebecca; Beauharnais, Carole Anne et al. (2009) CYP2B6 variants and plasma efavirenz concentrations during antiretroviral therapy in Port-au-Prince, Haiti. J Infect Dis 200:955-64

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