Electronic Thesis and Dissertation Repository

Thesis Format

Monograph

Degree

Master of Science

Program

Microbiology and Immunology

Supervisor

Prodger, Jessica L

Abstract

Penile circumcision reduces HIV susceptibility by up to 60% in men; however, many men prefer to remain uncircumcised for personal or cultural reasons. Penile circumcision protects against HIV by reducing anaerobic bacteria on the penis. Penile anaerobes cause local inflammation and the recruitment of HIV-susceptible CD4+CCR5+ cells, increasing the likelihood that exposure to HIV during intercourse results in infection. To determine if a non-surgical intervention can reduce penile anaerobes and HIV target cells, we randomized men to antimicrobial treatment prior to circumcision. To be able to quantify the effect of antimicrobials, we developed a novel deep-learning algorithm to quantify HIV target cells in immunofluorescent microscopy images of foreskin. We found that men who received antimicrobials had a lower density of HIV target cells, which correlated with reductions in penile anaerobes and secreted inflammatory mediators. These results suggest that microbiome-based interventions could be a potential tool for HIV prevention.

Summary for Lay Audience

Male circumcision has been shown to be able to reduce the risk of acquiring HIV by up to 60% in men. Despite these benefits, many at-risk men still choose to not undergo this procedure and it is not completely understood how circumcision can have a protective effect against HIV infection. One way that circumcision protects against HIV is by eliminating specific species of anaerobic bacteria that have been shown to recruit HIV-susceptible cells in the penis. To determine if a non-surgical intervention could similarly eliminate anaerobes from the penis, we completed a clinical trial testing the effect of commonly available antibacterial agents on penile bacteria and the abundance of HIV-susceptible cells in penile tissue. To accomplish this, we developed a machine learning program to automatically analyze and quantify HIV target cells in microscopy images generated from tissues collected after the course of antimicrobials. We found that antibiotic treatments reduced penile bacteria, inflammation, and abundance of HIV-susceptible cells. The results from this study shown that antibiotic treatment could be used as a potential tool for HIV prevention.

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