Mapping the Microbiome: Vaginal Bacteria and HIV Risk
September 21, 2016
University of Washington Findings
But CAPRISA's wasn't the only vaginal bacteria analysis presented at AIDS 2016. McClelland presented a poster of his team's findings -- which mapped the Prevotella genus, but not P. bivia.
Instead, the University of Washington found five other bacteria associated with statistically significant increases of HIV incidence in their cohort of people with vaginas (the studies were all conducted on non-trans women). Those bacteria were Eggerthella species type 1, Gemella asaccharolytica, Leptotrichia/Sneathia, Megasphaera, and Mycoplasma hominis.
The results were based on vaginal samples from 349 women, 87 of whom were living with HIV. Like the CAPRISA group, the University of Washington employed broad range 16S rRNA sequencing. In addition, the team analyzed both the relative abundance of a bacteria in the microbiome -- that is, what percentage of the total community was occupied by a particular strain -- as well as the absolute number of a particular bacteria present. Then the team did a quantitative PCR probe to zero in on the five bacteria with the highest association with HIV.
Differentiating between relative and absolute bacterial copies is important because the sheer volume of bacteria in a microbiome varies by woman, too, said McClelland.
"We saw [in a recent JAIDS paper] a 100-fold difference in overall vaginal bacteria concentration," he said. "A relative abundance of 1% in one woman might be 100 times more of that bacteria than in another woman, who has the exact same relative abundance."
And that concentration may be important to HIV risk, said McClelland -- though he said it's too soon yet to tell. University of Washington's data showed an association between abundance of bacteria and HIV susceptibility: Gemella asaccharolytica was most associated with HIV at the highest concentrations, but not at lower concentrations. Megasphaera, meanwhile, was associated with a three-fold increase of HIV -- but only at the smallest concentrations. Eggerthella species 1 had its highest association with HIV when present in mid-range quantities, but the association dropped off at either higher or lower concentrations.
The challenge now is to delve more deeply into the bacterial species and do more research to confirm and replicate the findings.
"What I'd love to know is if a high concentration of Gemella, for instance, is associated with having a low concentration of Megasphaera," said McClelland. "This might suggest that a particular bacterial community with both of these species in particular concentrations is associated with higher risk for HIV."
The findings were gratifying for McClelland, who said that the study was a risk. It could have turned out that any BV-associated species would increase HIV risk. And then we'd just be back at what researchers knew in 1998.
"I would have been disappointed had we simply ended up in the same old place --that there aren't individual taxa driving this, but that it's just all of them," he said. "I was delighted -- I would not say surprised, but delighted -- that, in fact, the data emerged that does support the hypothesis I first wrote into a grant nine years ago, that there may be key bacterial species associated with HIV acquisition."
Making Progress for Women
The lack of agreement between the two studies about which bacteria increase risk didn't trouble Douglas Kwon, M.D., Ph.D., who heads a research team on the vaginal microbiome and inflammation at Harvard Medical School. He called the disparities an example of the scientific method at work. All the results will need to be replicated around the world, anyway.
But he did think the results, as varied as they are, represented progress.
"For a while, we linked specific sexually transmitted infections [STIs] to increased HIV acquisition risk, and then more recently to baseline genital inflammation," Kwon said. "From the research presented, the emerging idea is that the vaginal microbiome increases HIV risk -- not just STIs, not just specific infections, but actually the community of microorganisms that live in the genital tract."
If that turns out to be true, he said, "that means attempts to manipulate the microbiome would be useful for reducing HIV risk in women in sub-Saharan Africa."
(Read more about ways researcher are attempting to manipulate the microbiome to boost women's natural HIV prevention here.)
But that's a big "if." Even McClelland said there's so much more to learn about this part of the body that we have to go back to the beginning, to basic science, to figure out what these results mean.
"These are observational studies, and so we have to ask the question: What are the other possible explanations for these associations?" McClelland said. "For example, in young women becoming sexually active, could these [bacteria] simply be a marker for unprotected sex, or unprotected sex with an uncircumcised, HIV-positive male partner? HIV may change the man's microbiome, too. Bacteria that are under the foreskin are part of the penile microbiome. From there, they may be passed into the vaginal microbiome of their partners."
As researchers move forward, he said, "it's important to be circumspect."
Heather Boerner is a health care journalist based in San Francisco and author of Positively Negative: Love, Pregnancy and Science's Surprising Victory Over HIV.
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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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