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Vaginal microbiome and HIV infections

Vaginal dysbiosis and bacterial vaginosis increase the risk of HIV infection

Dysbiosis of the vaginal bacterial flora is a key factor in vaginal inflammation, in the consistency of the epithelial barrier, and for the acquisition of HIV infection. Nichole Klatt, from the University of Washington, Seattle, presented current findings on the influence of vaginal microbiome on HIV transmission at the 25th CROI in Boston on March 6, 2018.

More than half of new HIV infections affect women. Every minute, two women worldwide are infected with the virus. "This means that during my 25-minute lecture 50 women will be infected with HIV," Klatt explained. Women tend to fall ill at a younger age. In parts of Africa, twice as many women as men between the ages of 15 to 24 suffer from AIDS. A particularity impacting women is the transmission of the disease from mother to child. There is also the problem of sexual violence and the rejection of protective measures such as condoms in some countries. "Another special challenge is that we have not yet fully understood the biological mechanism that leads to the acquisition of HIV in women," Klatt continues.

Microbiome and dysbiosis

The term microbiome covers all microorganisms colonizing humans such as bacteria, viruses, fungi, protists, and archaea as well as their genes, metabolites, and products. In dysbiosis, the microbial community is not in equilibrium, microorganisms are missing or functional changes are present. Microbial dysbiosis is associated with a variety of diseases. The largest and best-known microbiome in the body is the intestinal microbiome. Disorders in the intestinal microbiome are associated, for example, with colorectal cancer, diabetes mellitus, obesity, inflammatory intestinal diseases, neurological and metabolic diseases and HIV pathogenesis.

Microbiome in the vagina

Dysbiosis of the vaginal microbiome plays a role in vaginosis, sexually transmitted diseases, yeast infections, premature birth and HIV transmission. A normal vaginal microbiome is characterized by the dominance of lactobacilli and a relatively low pH value. Dysbiosis is dominated by anaerobic bacteria such as Gardnerella, Prevotella, Mobiluncus or Atopobium; the pH increases, inflammation increases, and the epithelial barrier is damaged. However, this is a relatively simple description of the vaginal microbiome and dysbiosis, the overall processes are much more complex. In addition, the composition of the vaginal microbiome varies depending on ethnicity. 

Bacterial vaginosis is a typical diagnosis of vaginal dysbiosis. It is the most common cause of vaginitis and is associated with a loss of Lactobacillus spp. and increased diversity in the vaginal microbiome. The typical antibiotic treatment is not effective, recurrences often occur. 

The vaginal microbiome is an important factor in HIV acquisition. Vaginal dysbiosis is much more common in areas with a high prevalence of HIV. For example, the vaginal microbiome of African women often contains fewer lactobacilli and more Gardnerella. It is now believed that vaginal dysbiosis and bacterial vaginosis increase the risk of HIV infection. 

What mechanisms play a role?

Vaginal dysbiosis is associated with inflammation. It can also reduce the integrity of the epithelial barrier. The Centre for the AIDS Program of Research in South Africa (CAPRISA-004 study) showed for the first time that a vaginal gel containing 1% tenofovir can reduce the risk of HIV infection by 39% compared to placebo. 

Klatt and her team then analyzed the vaginal flora of 688 women who had participated in the CAPRISA study. Lactobacilli dominated in about 60% of women and Gardnerella vaginalis in about 40%. The risk of HIV was reduced by 61 % in women with lactobacillus-dominant vaginal flora and by only 18 % of women with dysbiosis, i.e. Gardnerella-dominant flora. Less tenofovir was found in the mucosa of women with Gardnerella vaginalis dominance. 

Further studies showed that dysbiotic bacteria metabolized tenofovir and dapivirine more rapidly. Tenofovir alafenamide, however, is not metabolized by the dysbiotic bacteria. Klatt pointed out that other factors can impair the efficacy of the drugs, such as the inflammation present in the case of dysbiosis.

Klatt concludes that the effectiveness of preventive measures can be improved if the vaginal microbiome is understood and if it is clear how lactobacilli can be strengthened and dysbiosis prevented.

Source:
Klatt, N. The vaginal microbiome and acquisition of HIV infection. 25th CROI, Boston, March 6, 2018, Abstract 64. http://www.croiconference.org/sessions/vaginal-microbiome-and-acquisition-hiv-infection.