How Vaginal Microbial Dysbiosis Drives Women HIV Rates

March 10, 2018
Kevin Kunzmann

Two new women are infected with HIV every minute. How much of a role does dybiosis play in preventive treatment failure?

Nichole Klatt, PhD

Despite bounds of clinical development and new insights highlighting the past decade of HIV research, the biological associations between the virus and women populations is still a sought-after mystery.

The annual million-plus women newly infected with HIV remains an unprecedented rate — they comprise over 50% of all new infections, Nichole Klatt, PhD, from the University of Washington, said. Another way Klatt explained that frequency is that 2 women are infected with HIV every single minute.

In a lecture centered around this dilemma at the 25th Conference on Retroviruses and Opportunistic Infections (CROI) in Boston, MA, Klatt detailed a strong lead in the investigation of women’s HIV rates: vaginal microbial dysbiosis.

Dysbiosis, a microbial imbalance that could resemble a series of symptomatic issues in the gut, has a strong association with disease, and could affect HIV transmission rates in its vaginal microbiome form. Healthy microbiomes, such as the Lactobacillus dominant, is characterized by low pH levels and protective capabilities.

But in cases of dysbiosis, polymicrobial and anaerobic bacteria increases pH, inflammation, and barrier damage in patients. The end result is a greater susceptibility to sexually-transmitted diseases, Klatt said.

Vaginal dybisosis is frequently most prevalent in areas of greater HIV infection rates in women, Klatt noted. While regions of North America have more frequent rates of healthy microbiomes than dysbiosis, the contrary is true for Sub-Saharan Africa — a hub of HIV infection in women.

In that particular African region, women between the ages of 15 and 24 are more than twice likely to be infected HIV compared to males of the same age group. Klatt added that residents of underdeveloped countries face even more obstacles in virus prevention: sexual violence rates are notably higher, and limited understanding of the biological mechanisms involved in the virus transmission burden these regions.

That said, vaginal microbiome makeup varies across ethnicities. Klatt noted one study which found that white women often have more Lactobacillus in the microbiome than black and Hispanic women, who often more diverse dysbiotic communities.

“This is why I hesitate and I kind of use quotes when I say ‘healthy’ or ‘good’ [microbiome] because we don’t really know,” Klatt said. “Many women around the world have dysbiosis or these highly diverse communities, and so it may not necessarily be a bad thing; however, for HIV transmission it does seem to play a role.”

Microbiome dysbiosis is clinically diagnosed as bacterial vaginosis (BV), though a diagnosis of the former does not indicate the latter, and vice versa. Klatt noted another study which found that a group of female patients with healthy Lactobacillus had no HIV infection risk. But with increases of microbiome diversity, virus risk increased. The study also found that women with BV had an increased rate of HIV infections.

“It’s not just that women who have BV are at higher risk of HIV infection, but also, a man sleeping with a woman who has BV has a higher risk of HIV infection,” Klatt said. “There’s also a higher risk of mother-to-child transmission with a woman who has BV, and so, it’s an important problem and it’s something that we have to understand better.”

Klatt also stressed that more needs to be understood on how vaginal microbiome affects pre-exposure prophylaxis (PrEP). Aside from adherence rates, biological factors may be to explain why PrEP delivers 80% to 90% efficacy in men, and only 50% to 75% efficacy in women.

In reviewing the CAPRISA 004 trial results — which studied the influence of a topical microbicide on tenofovir gel PrEP — Klatt and her team found the gel was 39% effective overall in reducing HIV infection in women participants. But the effectiveness greatly varied when split across women with dysbiotic Gardnerella dominance (18%) and Lactobacillus dominance (61%).

Klatt eventually found that Gardnerella dysbiotic bacteria infection likely enhances HIV infection by metabolizing the tenofovir PrEP before it could affect target cells.

“Dysbiosis of vaginal bacteria is a key factor in vaginal inflammation, epithelial barrier integrity, and HIV acquisition,” Klatt said. “Dysbiotic bacteria can metabolize the PrEP drugs tenofovir and dapivirine and potentially contribute to decreased PrEP efficacy in vivo.”

Klatt called on improved drug efficacy, using her and other’s research on dybiosis as a foundation, to better the prevention and care of women at risk for and with HIV.

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