Vaginal bacteria could play a key role in regulating HIV risk among women
Understanding the vaginal microbiome and how it impacts HIV risk could help develop more effective treatment and prevention strategies for young women in sub-Saharan Africa.
The composition of vaginal bacterial communities can have a significant effect on the risk of acquiring HIV, according to new research carried out among black South African women.
The research, published in the journal Immunity this week (January 10), found that women with highly diverse low-Lactobacillus bacteria populations had four times as many new HIV infections as those with low diversity bacterial communities dominated by Lactobacillus.
Lactobacillus is a ‘friendly’ bacteria found in the digestive, urinary and genital systems. Researchers typically consider Lactobacillus-dominant microbiomes to be ‘healthy’ – although much of this understanding stems from research conducted on white women living in high-income countries, where 90% are thought to be Lactobacillus-dominant. It may not be true for all women, particularly in sub-Saharan Africa, where diverse low-Lactobacillus bacterial communities have been shown to be more prevalent.
The research may start to shed some light on the biological factors that contribute to young women living in sub-Saharan Africa having an eight-fold increase in HIV prevalence over young African men. Globally, young African women are among the groups most affected by HIV.
It had previously been known that inflammation in the female genital tract increased risk of HIV acquisition, and that vaginal bacteria could play a role in regulating this risk. Until recently, studies exploring this risk were limited, but the development of better sequencing technologies is now allowing for a better understanding of how vaginal bacteria could affect disease progression.
Using this sequencing, the researchers attempted to understand the role of vaginal bacterial communities on HIV susceptibility among a cohort of 236 HIV-uninfected black South African women, aged 18-23 years, participating in a poverty-alleviation study.
Among the participants, the researchers identified four distinct vaginal bacterial communities (also called cervicotypes). Two of the cervicotypes (CT1 and CT2) were defined by low diversity bacterial communities dominated by Lactobacillus. Just 42% of the black South African women had Lactobacillus-dominant cervicovaginal communities.
The remaining 58% of women had cervicotypes comprising highly diverse low-Lactobacillus bacteria populations. CT3 was dominated by Gardnerella vaginalis, and CT4 was dominated by bacteria other than Lactobacillus and Garnerella – the most common being Prevotella, Gardnerella, Shuttleworthis, Sneathia and Megasphaera.
The researchers found that over the course of a year, the women with highly diverse low-Lactobacillus bacteria populations had four times as many new HIV infections as those with low diversity bacterial communities dominated by Lactobacillus. This increased risk was independent of factors such as sexually transmitted infections (STIs), condom use and sexual behaviour.
Furthermore, women with high diversity bacterial communities had increased levels of activated CD4+ T cells in their female genital tract. CD4+ T cells are those that HIV attacks and are a known biological marker of HIV susceptibility. Between CT1 and CT4 in particular, there was a 17-fold increase in the number of these cells in the vagina.
Certain bacteria were also closely linked to increased and decreased inflammation and HIV acquisition. Notably, Lactobacillus crispatus was associated with decreased HIV infection risk, and the bacteria taxa, Prevotella and Sneatha, were associated with increased HIV acquisition and inflammation.
The authors note that this reduced acquisition with Lactobacillus crispatus could be the result of the ability of this bacteria to limit inflammation and thus the number of CD4+ T cells. This was validated by the fact that no women with Lactobacillus crispatus-dominant communities acquired HIV.
To further demonstrate the link, the researchers introduced Prevotella biva and Lactobacillus crispatus into the vaginas of two groups of mice. In the mice inoculated with Prevotella biva, there was increased CD4+ T replication, showing that certain bacteria does increase HIV susceptibility.
“Our findings demonstrate the importance of considering the genital microbiome in the development of new strategies to reduce HIV acquisition in women living in sub-Saharan Africa,” said lead author Christina Gosmann, PhD, of the Ragon Institute at Harvard University in the USA.
"By identifying both bacterial communities and individual bacterial species associated with HIV risk, we can provide specific targets for the development of preventive strategies," she continued. "In addition, treatments targeting genital bacteria could improve the effectiveness of existing preventive measures.”
The research leaves open questions as to why women have different cervico bacterial communities, particularly between geographies. Possible differences in biology of the vaginal microbiome could explain this in part, as well as behavioural factors, although these links need further research.
Other studies have pointed to certain vaginal practices prevalent in sub-Saharan Africa that could increase HIV risk. A range of behavioural practices to maintain perceived vaginal hygiene and improve sexual pleasure for their partners have been identified – including intra vaginal cleansing and the drying out of the inside of the vagina. These cultural practices could alter the vaginal microbiome and induce inflammation, providing an environment which increases HIV risk.
Understanding the vaginal microbiome and how it could impact viral and disease progression may provide key insights for the development of treatment and prevention strategies for young women living in sub-Saharan Africa.