New evidence on why some women are more at risk for HIV infection

Two independent studies from the University of Manitoba, University of Washington, and Northwestern University published in PLoS Pahogens provide new information on the importance of epithelial barriers in susceptibility to HIV infection – one showing how epithelial barriers modulate HIV virus migration and target cell accessibility and the other showing vaginal bacteria linked with HIV risk disrupt epithelial barriers and impair wound healing.

Young women around the world, and especially in Africa are at high risk of acquiring HIV. Epidemiological studies have suggested that the contraceptive Depo Provera and bacterial vaginosis can both increase this risk.

These studies begin to provide insights into how certain contraceptives and bacterial vaginosis can increase acquisition. Importantly, alternative contraceptive choice and treatment of bacterial vaginosis can be used by young women to potentially decrease their risk of HIV infection. The mechanistic insights from this work can inform public health officials to make new recommendations that could decrease infection and stem the HIV/AIDS pandemic.

A team lead by University of Manitoba medical microbiologist Adam Burgener and University of Washington pathobiologist Nichole Klatt investigated how vaginal bacterial communities, particularly bacterial vaginosis, affected the epithelial barriers of the vaginal tract. (This is the second time they have teamed up.)

It has been well established that bacterial vaginosis, characterized by a shift from Lactobacillus species to highly diverse bacterial communities containing Gardnerella and other anaerobic bacteria, is associated with increased risk of HIV infection.

Utilizing advanced proteomics techniques, they examined mucosal secretions from women with and without clinical bacterial vaginosis, and found that molecular pathways important for stratum corneum formation and epithelial integrity were affected when Lactobacillus was in low abundance. By using culture techniques they found G. vaginalis inhibits the ability of genital tract epithelial cells to close and heal wounds, while Lactobacillus would facilitate this healing. This provides a potential mechanism by which Lactobacillus protects from HIV infection, while Gardnerella can induce breaching in the epithelial barrier, allowing HIV to penetrate.

In the second study, using a non-human primate model, Thomas Hope, a professor of cell and molecular biology at Northwestern University, and his team examined the impact of Depo Provera (DMPA) on SIV (HIV) infection to better understand the linkage between DMPA usage and/or the menstrual cycle and increased HIV susceptibility in women. Using advanced cellular imaging and fluorescent virus technology, they found that DMPA usage or the luteal phase of the menstrual cycle resulted in the shedding of a superficial layer of keratinized epithelial cells, called the stratum corneum, normally protecting the skin of the vaginal vault. Further, the loss of this layer let to the infiltration of target cells and changes in mucus that increased the likelihood of HIV virions to contact target cells, allowing for the virus to start an infection.

“Both of these studies reveal how hormonal changes, or how vaginal bacteria, can impact wounding mechanisms in the female genital tract that could impact HIV acquisition in women,” Burgener says. “We are excited that these advanced tools are identifying new avenues for treatment or strategies to help women decrease their risk of HIV infection.”

These studies provide information scientific evidence, using state-of-the-art technologies, that is paradigm shifting and show the significance of an intact and functional skin barrier in the genital tract is critical to decrease HIV susceptibility. These studies provide new avenues for exploration for HIV prevention strategies in women given the widespread use of progestin-based contraceptives and high prevalence of bacterial vaginosis.

UM Today, in partnership with Northwestern University and University of Washington