HIV Transmission in the Female Genital Tract

Globally, more than 90% of HIV is transmitted following heterosexual intercourse; women being twice as likely to contract HIV from heterosexual sex than men. In the majority of new infections, the mucosal tissue of the female reproductive tract (FRT) is the primary site for HIV infection and the initial site of viral replication.  A better understanding of the immunological environment of the FRT is crucial to the development of new intervention strategies to help halt HIV transmission amongst sexually active heterosexual women.

Recent results from the CAPRISA 004 vaginal microbicide trial suggest that elevated FRT inflammation increases risk of HIV acquisition by over 3-fold. Microbially-driven sexually transmitted infections (STIs), bacterial vaginosis (BV), and reproductive hormones are known modulators of genital inflammation and increased HIV acquisition risk, suggesting the vaginal microbiome more broadly may play important roles in engendering FRT inflammation.

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 FRT and may contribute to inflammation. New high throughput sequencing (HTS) technologies can comprehensively characterize the bacterial microbiome but have not been applied to the assessment of the entire vaginal microflora. The mechanism by which reproductive hormones, including endogenous progesterone and depot medroxyprogesterone acetate (the most common form of hormonal contraception used in sub-Saharan Africa), increase HIV acquisition remains incompletely understood. Collectively, we believe both microbial and hormonal factors can significantly affect FRT inflammation and therefore potentially increase HIV acquisition in women. To fully define optimal strategies to prevent HIV transmission, a more complete understanding of the interdependent role of the vaginal microbiome, reproductive hormones, and genital inflammation is needed.

Furthermore, the majority of microbiome studies, including those focusing on the FRT, have been performed on women of North American or European ethnicity. This raises questions of how informative previous vaginal microbiome studies are to identify the microbial drivers of inflammation in the FRT and subsequent increased HIV acquisition risk. 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. Therefore, strain profiling of the vaginal microbiome of the women in at-risk areas is crucial to developing appropriate interventions for microbial community engineering such as targeted antibiotics, pro- and pre-biotics.