HIV Transmission in the Female Genital Tract

Young women bear a disproportionate burden of the HIV epidemic, with HIV prevalence rates up to 8-fold higher in young women compared to young men in many sub-Saharan African countries. In the majority of new infections, the mucosal tissue of the female genital tract (FGT) is the primary site for HIV infection and the initial site of viral replication.  A better understanding of the impact of the immunological environment of the FGT on HIV risk is therefore crucial to the development of new strategies to halt HIV transmission in women, particularly those living in sub-Saharan Africa.

Results from a number of studies suggest that elevated FGT inflammation increases risk of HIV acquisition. Microbially-driven sexually transmitted infections (STIs), bacterial vaginosis (BV), and reproductive hormones are known modulators of genital inflammation and increased HIV acquisition risk. We have applied next generation sequencing technologies to characterize the vaginal microbiome in young women in sub-Saharan Africa and demonstrated that the majority of these women have microbial communities that are very different from those of women living in resource rich settings. We further demonstrated that specific communities drive genital inflammation and result in an over 4-fold increased risk of HIV acquisition. This suggests that the vaginal microbiome may be leveraged to reduce HIV acquisition in young women in sub-Saharan Africa.

The characterization of the vaginal microbiome to date has largely focused on the bacterial component, however other domains of life, including fungi, viruses, and potentially as-yet-incompletely-defined organisms, inhabit the FGT and may contribute to inflammation. We have therefore moved beyond characterization of bacteria by using shotgun sequencing to comprehensively characterize other microbial populations within the FGT.  Furthermore, the majority of microbiome studies, including those focusing on the FGT, have been performed on women of North American or European descent. This raises questions of how informative previous vaginal microbiome studies are to the identification of the microbial drivers of inflammation in the FGT of women living in different geographies. Several gut microbiome studies have shown strong geographical trends in bacterial sub-species structures whereas others have shown a host genetic component to microbial community structure. We are therefore studying women living in a number of different geographies and performing strain profiling of the vaginal microbiome. We are combining this with studies of microbial function, bacterial engineering, and deep characterization of host microbial sensing and mucosal immunity to develop interventions  to reduce HIV infection in women.