Mapping the Microbiome: Vaginal Bacteria and HIV Risk
September 21, 2016
Some bacteria might also increase risk, at least according to evidence presented at last month's International AIDS Conference (AIDS 2016) in Durban, South Africa. In two separate presentations by two different teams, researchers showed that half a dozen bacteria that are more prevalent among African women might increase HIV susceptibility. But how to remove those bacteria is more complicated, and researchers don't yet have a good solution.
"Some women are going to acquire HIV irrespective of their vaginal microbiomes," said R. Scott McClelland, M.D., M.P.H., associate director of the University of Washington's Center for AIDS Research, who presented one of the studies at AIDS 2016. "But I really think that the vaginal microbiota does drive the vaginal immune milieu, and I think it does influence susceptibility to HIV."
A 20-Year-Old Hypothesis
The vaginal microbiome is a "good news/bad news" kind of situation when it comes to HIV.
On the one hand, researchers have known for years that women with a microbiome dominated by one specific bacterial type, Lactobacillus, had lower rates of HIV. (Details about that are available here.) They've also known that women with HIV-protective microbiomes tend to be white and Asian.
On the other hand, women without Lactobacillus dominant microbiomes -- women with a great diversity of bacterial types, a condition doctors generally call bacterial vaginosis (BV) -- tend to be African American, Latinx or live in sub-Saharan Africa. In other words, BV is more common among people and in areas with the highest HIV rates.
But it's not just geography. BV is itself strongly associated with HIV acquisition, presumably because it increases inflammation in the vagina, which attracts more immune cells to the vaginal surface -- cells that HIV then hijacks. A meta-analysis published in AIDS in 2008 found that women with BV were 60% more likely to have HIV.
This has been a problem for researchers because diverse microbiomes are difficult to dislodge.
"[BV] has been mysterious," said Richard Cone, Ph.D., a biophysicist who has run a lab at Johns Hopkins University for years, looking for ways to harness the vaginal microbiome to protect women from HIV. "We don't know what starts it. We don't know how to help women get over it. It's recurrent."
Researchers have been looking at the vagina for about two decades, trying to decipher whether it's just BV -- that is, lack of Lactobacillus -- that increases women's HIV risk, or whether it's something more specific. So, when McClelland and the Center for the AIDS Programme of Research in South Africa (CAPRISA) discussed their findings at AIDS 2016 in July, their presentations were 20 years in the making.
While there were two presentations at AIDS 2016, only one got spotlight status. AIDS 2016 convened a special symposium, chaired by U.S. Ambassador Deborah Birx and National Institute of Allergy and Infectious Disease Director Anthony Fauci, M.D., to present data from CAPRISA.
That study found that, while women have a variety of bacteria in their microbiomes, one bacteria, Prevotella bivia, was associated with a 13-fold increased risk of HIV. But the results represented a small sample -- 11% of 119 women who had participated in CAPRISA's trials of an HIV-prevention gel. And, because it was a symposium, the methodologies weren't available for conference attendees to analyze. A question-and-answer session was planned for the end of the symposium, which presented data on three interlinked studies on women's HIV risk, but time constraints made that impossible, said Brent L. Williams, Ph.D., an assistant professor of clinical pathology and cell biology at Columbia University.
Williams conducted the bacterial sequencing and analysis for the CAPRISA study. In an email, he explained that the analysis was based on broad-range 16S rRNA sequencing, which can analyze the abundance of a specific bacteria in a woman's microbiome, relative to the other bacteria in the vagina. That is, the study didn't just check that the bacteria existed at all; it also ascertained the relative amount of P. bivia in the microbiome compared with other bacteria present.
That was followed by shotgun metagenomic sequencing in a subset of samples to double check the 16S sequencing's findings, as well as a quantitative PCR using primers specific to P. bivia, to ascertain the absolute number of P. bivia copies in each woman's microbiome.
"Both the 16S rRNA sequencing and quantitative PCR with an assay specific for Prevotella bivia revealed the strong association with inflammation and HIV acquisition," Williams stated. "This layered approach, using a combination of methodologies, while laborious, provides us as scientists with statistical rigor required to fully validate the findings."
Williams said he'd been working on it for three years.
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This article was provided by TheBodyPRO. It is a part of the publication The 21st International AIDS Conference (AIDS 2016).
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