Evidence suggests that women who are naturally resistant to HIV infection exhibit low baseline immune activation at the female genital tract (FGT). This “immune quiescent” state is associated with lower expression of T-cell activation markers, reduced levels of gene transcription and pro-inflammatory cytokine or chemokine production involved in HIV infection while maintaining an intact immune response against pathogens.
Therefore, scientists at the University of Waterloo hypothesized if this unique immune quiescent state could somehow be pharmacologically induced locally, it could provide an excellent women-oriented strategy against HIV infection.
HIV can only replicate in the human body after it attaches to the surface of one of several types of white blood cells – or lymphocytes – whose purpose is to detect and destroy pathogens. Thus, although it may sound counter-intuitive, inhibiting the immune system’s reaction against viral particles present in the female genital tract actually interferes with the virus’s ability to gain its initial foothold in the body.
“We know that some drugs taken orally never make it to the vaginal tract, so this implant could provide a more reliable way to encourage T cells not to respond to infection and therefore more reliably and cheaply prevent transmission,” said Emmanuel Ho, a professor in the School of Pharmacy at Waterloo. “What we don’t know yet is if this can be a stand-alone option for preventing HIV transmission or if it might be best used in conjunction with other prevention strategies. We aim to answer these questions with future research.”
The team thereby designed an implant composed of a hollow tube and two pliable arms to hold it in place. It contains hydroxychloroquine (HCQ) which is disseminated slowly through the porous material of the tube and absorbed by the walls of the vaginal tract.
The implants were tested in an animal model and the team observed a significant reduction in T cell activation, meaning that the vaginal tract was demonstrating an immune quiescent state.
