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Bacteria making HIV prevention drugs less effective in African women, UM team finds

August 12, 2016 — 

A team of international researchers, including U of M’s Adam Burgener, presented evidence last month that certain bacteria are culpable in the high rates of HIV infection in young South African women.

The researchers, in partnership with Public Health Agency of Canada and  the Centre for the AIDS Programme of Research in South Africa (CAPRISA), presented their findings at the AIDS 2016 Conference in Durban in July.   This study was funded by a research grant to Dr. Burgener’s lab from the Canadian Institutes of Health Research.

The U of M findings

More than one million women are infected annually with HIV, with the majority of these new infections occurring in young women in sub-Saharan Africa, with South African being among the highest HIV incidence rates.

Pre-exposure prophylaxis (PrEP), utilizling antiretroviral drugs, has been investigated as a strategy to prevent HIV transmission in men and women.  However, while PrEP has shown consistency in men, this has been very variable in trials in women, and it was not known why women needed such high adherence to the drugs.  Dr. Burgener’s team investigated what role bacteria in the genital tract may be playing in this process, using state-of-the art proteomics techniques.

Burgener and his students — Kenzie Birse, Michelle Perner, and Laura Romas — ran an analysis of 3,334 genital bacterial proteins from 688 women who were part of a trial that evaluated the effectiveness of 1 per cent tenofovir-continaing vaginal gel at protecting against HIV (CAPRISA-004). The results showed that three out of five women who had a “healthy” lactobacillus dominant vagina showed that tenofovir gel PrEP was effective in preventing HIV, while the women who did not have lactobacillus dominance, showed little benefit from the gel.

“This was a striking result, and made us think that there was some interaction between some bacteria and tenofovir,” says Burgener.

This lead to follow up laboratory studies, in partnership with Dr. Nichole Klatt’s lab at the University of Washington, to investigate if the vaginal bacteria were interacting with the drug.  The experiments showed that Gardnerella vaginalis, which predominates in the vagina when lactobacillus levels are low, metabolizes tenofovir thereby reducing the availability of the drug to prevent HIV infection.

“It was astonishing to see that Gardnerella quickly metabolized the drug and depleted it from culture, and was really a smoking gun as to why women these women may not be protected,” Burgener says.

In short, this was the first study lead by Burgener’s team to show that vaginal bacteria can impact PrEP efficacy, and that PrEP efficacy can vary more than three-fold contingent upon Lactobacillus being the dominant organism.

Burgener explains that since Gardnerella is highly prevalent in African women, this has important clinical implications on how PrEP is implemented in women.  Simple tests, such as vaginal pH screening, could be utilized to identify women that would benefit most from PrEP.

Prior to this finding, it was thought the gel was not working well due to women incorrectly applying it, or not frequently enough. But the U of M team showed that vaginal bacteria are likely a large contributing factor, giving researchers an new avenue to explore.

“We hope to expand these studies to see how vaginal bacteria may affect other HIV prevention drugs in previous trials, as well as new drugs in development, and has really opened our eyes to the impact of the microbiome on HIV transmission in women,”  Burgener says.

Where to go from here

Since Gardnerella bacteria raise the vaginal pH, a readily available, quick, simple and cheap test can be used to ascertain which women would benefit from PrEP and those that would require other strategies to promote vaginal Lactobacillus. Combined, these interventions could have a significant impact on the spread of HIV in women in South Africa and beyond

Research at the University of Manitoba is partially supported by funding from the Government of Canada Research Support Fund.

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