Infections of the female genital tract can increase the risk of women acquiring HIV. The inflammatory bacteria may leave them four times more vulnerable to being infected with the virus.

The total of people living with HIV globally now reaches 36.7 million. 24 million of these live in sub-Saharan Africa, where the majority of new transmission events occur following heterosexual sex.

Studies have shown that in this region of the world, young women have an increased HIV prevalence compared to young men. This means there is a need for more research to investigate why such women are more likely to be infected with HIV.

Elevated inflammation due to certain types of bacteria in the cervix and the vagina is associated with increased HIV risk. However, the role of these bacteria in HIV susceptibility remains unclear.

The study published in the journal Immunity investigated this question, analysing the type of bacteria present in the genital tracts of a group of South African women.

Greater number of genital white blood cells

The scientists recruited 236 HIV-uninfected women for their study, and followed them for a median time of 336 days. All received HIV prevention counselling as part of the research, but 31 women nevertheless acquired HIV.

The researchers analysed genital samples and sequenced bacterial genes present in the genital tracts of the participants. They found that women with highly diverse genital bacterial communities dominated by pro-inflammatory species of bacteria, and with low Lactobacillus bacteria abundance, were at over fourfold higher risk of acquiring HIV.

"Seventy percent of our volunteers had diverse bacterial communities with low Lactobacillus abundance. Here we show that not only are those more diverse communities associated with higher levels of genital inflammation, but also with significantly increased HIV acquisition", says senior author Douglas Kwon, from the Ragon Institute of MGH, MIT and Harvard.

lactobacillus
Most of the women in the study had low lactobacillus abundance in their genital tract.Janice Carr/CDC/Dr. Mike Miller

They also discovered that these women had a greater number of genital CD4+ T cells - the white blood cells which constitute HIV's primary target. Using a mouse model, the scientists showed that introducing the pro-inflammatory bacteria identified in the study into the genital tract of the animals also increased the numbers of activated genital CD4+ T cells.

These findings suggest that highly prevalent pro-inflammatory genital bacteria increase HIV risk by activating the cells targeted by the virus.

Vaginal health

The study's authors hope their findings can serve as the basis for new research to reduce HIV acquisition in sub-Sahara African wome, for example, by finding therapeutic solutions to make their genital tract become more Lactobacillus dominant. The study could also help scientists reconsider what they know about the female genital tract, and what constitutes vaginal health.

"We think of a healthy microbiome as being Lactobacillus dominant - that's what we are taught in medical school - but those studies are mostly based on white women in developed countries. When we did our first study we found that less than 10% of the women in our South African cohort had this classically 'healthy' community," Kwon points out.

It is still unclear what causes the differences between women's vaginal microbiomes. Genes as well as environmental factors - such as diet, hygiene and sexual behaviours - may play a role, but more research will be needed to find this out.