Inflammation of Innate Immune Responses in the Female Genital Tract: Association with Use of Injectable Progestin-Only Contraception, Reproductive Tract Infections and Risk of HIV Acquisition Public Deposited

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  • March 19, 2019
Creator
  • Deese, Jennifer
    • Affiliation: Gillings School of Global Public Health, Department of Epidemiology
Abstract
  • The successes and failures of many HIV prevention trials, including those of microbicides, antiretrovirals and vaccines, have led to a renewed interest in the biological mechanisms at the site of HIV infection. In women, the anatomical site of exposure and first infection is most often the vaginal and cervical mucosa.[1] Well accepted biological risk factors for HIV infection in women include mucosal disruption; immune factors, including the availability of CD4+/CCR5+ cells types; sexually transmitted infections (STI) and disturbances in the vaginal biome (e.g., bacterial vaginosis (BV)).[2] More recently, the profile of innate immune biomarkers - including cytokines, chemokines and antibacterial proteins - and associated levels of cellular activation have become a focus of interest as a potential mechanism of increased HIV risk. The results of prior studies in this area are varied, and additional research is needed. Potential reasons for the variability in results includes use of different specimen collection methods, methodological and analytical differences, statistical consequences (the increased probability of finding significant, yet spurious, associations in the case of measurement of multiple outcomes and multiple hypothesis testing) and differential selection of endpoints. Stored specimens from FEM-PrEP trial participants offered an opportunity to overcome some of the aforementioned challenges in studying the relationship between inflammatory cytokines, chemokines and antibacterial proteins with HIV and associated risk factors. FEM-PrEP was a Phase III, randomized, double-blind, placebo-controlled effectiveness and safety trial to assess the role of emtricitabine/tenofovir disoproxil fumarate (FTC/TDF, i.e., Truvada) in preventing HIV acquisition in women. FEM-PrEP was conducted in Bondo, Kenya; Pretoria and Bloemfontein, South Africa; and Arusha, Tanzania.[3] The trial enrolled HIV-negative women between the ages of 18-35 who met medical and behavioral eligibility criteria including being at high risk of HIV. Using stored specimens from the trial we estimated innate immune biomarker concentrations among Kenyan and South African women at high risk of HIV infection in the absence of known risk factors, and explored the association of those risk factors on biomarker concentrations, and analyzed elevated innate immune biomarker concentrations as a risk factor for HIV infection in a longitudinal analysis.
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  • In Copyright
Advisor
  • Behets, Frieda
  • Taylor, Douglas
  • Cohen, Myron
  • Morrison, Charles
  • Miller, William
Degree
  • Doctor of Philosophy
Degree granting institution
  • University of North Carolina at Chapel Hill Graduate School
Graduation year
  • 2015
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  • Chapel Hill, NC
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