Prevention of HIV transmission Public Deposited

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  • March 22, 2019
Creator
  • Chateau, Morgan
    • Affiliation: School of Medicine, Department of Microbiology and Immunology
Abstract
  • The human immunodeficiency virus (HIV) infects and replicates within individuals for the duration of their life. Initial infection results in little to no symptoms for years or even decades. These individuals are infectious and capable of further spreading HIV while completely unaware of their own status. This ability to transmit without detection is what lead to the unknown and thereby unopposed global spread of HIV type one (HIV-1). Once a test was developed to detect HIV, the virus was found in nearly all major countries around the world. Development of a cure has proven to be exceedingly difficult. So far, the only successful tactic to reduce the number of infected HIV individuals has been to prevent HIV transmission. Traditionally, the most effective way to prevent viral transmission is with a vaccine, but an effective HIV vaccine for wide spread use has not been developed. Therefore, alternative HIV transmission prevention strategies have been used. These strategies largely depend on behavioral modifications and include: 1) utilization of universal precautions in medical settings, 2) increased emphasis on HIV testing and self awareness of infection status, 3) encouraged use of protective measures such as condoms and male circumcision, 4) prophylactic use of antiretroviral drugs to limit mother to child transmission MTCT, and 5) the newly available oral pre-exposure prophylactic use of Truvada in HIV negative individuals. Together, these strategies have contributed to nearly eliminating HIV transmission in medical settings and greatly reduced MTCT. Unfortunately, HIV continues to spread globally largely due to sexual transmission. While condom usage is highly efficient to prevent transmission, their use is limited by acceptability and consent. In this dissertation, I evaluated the potential of topically applied interventions to be a novel, effective form of protection against HIV transmission as well as established a novel line of investigation evaluating microbial contributions to HIV transmission. Using humanized mice as a model of HIV transmission, I evaluated two antiretroviral drug based topical pre-exposure prophylaxis (PrEP) for efficacy; tenofovir and maraviroc. In both instances, these drugs were found to be protective when used prior to HIV exposure. Concerns regarding the dual use of tenofovir for treatment as well as PrEP prompted me to evaluate transmission of a tenofovir resistant strain of HIV. This study demonstrated a surprisingly large defect in transmission for tenofovir resistant HIV, which suggests that use of Tenofovir for PrEP may not result in a significant increase of circulating tenofovir resistant strains of HIV. I also utilized the humanized mouse model to start a completely novel line of investigation evaluating the effect of microbial populations on HIV transmission. While these studies are ongoing, preliminary results have shown a clear effect of microbiome composition on rectal HIV transmission. These results are significant in two ways. First, this is the first evidence that humanized mice are viable tools for microbiome based studies. Second, commensal microbiota does affect HIV transmission efficiency. Taken together, the following dissertation supports further efforts to curb the HIV epidemic by development of topical interventions (microbicides) and lends credence toward interventions based on commensal microbiome manipulations.
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  • In Copyright
Advisor
  • Garcia, J. Victor
Degree
  • Doctor of Philosophy
Graduation year
  • 2014
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