Harnessing Vaginal Microbiota to Protect Women From HIV: What We Know and Don't Know
March 16, 2017
Oral Tenofovir Works Regardless of Vaginal Microbiome, but Topical Applications May Not
So, if the microbes that live in the vagina can help or hinder HIV risk, do those microbes matter when it comes to HIV prevention? CAPRISA's Salim raised this question at the International AIDS Conference last year when, in addition to showing that P. bivia is associated with higher HIV prevalence in women, he showed that another microbe, Gardnerella, ["was just gobbling up" http://www.pbs.org/newshour/updates/bacteria-stoking-hiv-cases-blocking-hiv-treatment/] tenofovir (Viread) gel, leaving less to protect women from HIV.
This raised the question of whether the microbiome could blunt the effectiveness of other HIV prevention methods containing tenofovir, such as oral Truvada (tenofovir/emtricitabine). Plus, some researchers were just plain skeptical of Gardnerella's tenofovir-gobbling abilities.
So, at CROI, researchers presented the first evidence to either support or disprove Karim's findings.
First, Renee Heffron, Ph.D., M.P.H., an assistant professor of global health and epidemiology at the University of Washington and an investigator on the PARTNERS pre-exposure prophylaxis (PrEP) trial, took the samples they'd collected from women over the years and tested them for Gardnerella, the absence of Lactobacillus and other signs of BV. Then, they looked at the HIV acquisition rates among the women by vaginal pH and BV status.
What they found was that even though 24% of participants met the criteria for BV, there was no significant difference in oral tenofovir efficacy between groups. Essentially, what's happening in the microbiota has no influence on tenofovir when it's taken systemically.
But what about when it's applied topically? The CAPRISA tenofovir gel study ended several years ago, and a few tenofovir gel-based vaginal rings are in early development, so the absorption rate of tenofovir by the microbes in the vagina might still matter.
So, Sharon Hillier, Ph.D., at the University of Pittsburgh Magee Women's Research Institute, took the samples she had from her organization's participation in the CAPRISA study, tested them for presence of Gardnerella and Atopobium vaginae and assessed trough tenofovir concentrations after six days of gel use.
"I was surprised," Hillier said. "I had some skepticism about the [IAC] data, it's safe to say."
She didn't expect to see a difference by BV status, but there was. In fact, Gardnerella did, indeed, seem to reduce the amount of tenofovir gel available for protection, both in the cervicovaginal fluid and in blood plasma. The same was true of Atopobium vaginae.
This doesn't mean topical tenofovir couldn't be effective in women with BV, Hillier told TheBodyPRO.com. It could just mean that dosing of the drug would have to be more frequent if women have BV.
"But it's obviously not good," she said. "Anything that decreases the available drug isn't good."
What This Means for Women and Their Providers
At the beginning of his presentation, McClelland showed the audience a Venn diagram of the bacterial diversity that can make up BV. In the upper left hand corner was a circle with the bacteria M. hominis in it. In the lower left, were BVAB2 and Megasphaera species; in the lower right was Prevotella timonensis; in the upper right were Prevotella buccalis, Prevotella disiens and BVAB1. In the Venn diagram these species didn't overlap. M. hominis is associated with higher vaginal pH, but not with clue cells. BVAB2 is associated with clue cells but not with a positive whiff test -- in other words, the odor associated with BV. And P. disiens is associated with odor but not with vaginal discharge, which is the purview of P. timonensis.
Only Leptotrichia amnionii and Eggerthella on his slide hit all the marks.
"Different bacteria have different clinical effects on the cardinal signs and symptoms of BV," he said.
This is important for two reasons: One, McClelland said that presence of asymptomatic BV is associated with increased acquisition of other sexually transmitted infections (STIs), such as herpes, which in turn has been found to increase the likelihood that a woman will acquire BV over time. Both further increase women's risk for acquiring HIV.
Two, HIV risk doesn't decrease when a woman is asymptomatic. In a poster presented at the conference, researchers from ICAP at Columbia University in New York City asked whether waiting for symptoms to test for reproductive tract infections might be "antiquated in the HIV era."
What they found was that of the 314 Tanzanian women living with HIV in the study, 37.3% reported symptoms of reproductive tract infections, including BV. But when they tested all the women for STIs, they found that 78.7% of women actually had an STI. Syndromic diagnosis, they concluded, underestimates infections significantly.
This led one provider to ask McClelland why clinical guidelines don't reflect this evidence.
"Current guidelines state that if the symptoms resolve, no follow up is needed for bacterial vaginosis," the provider said. "But given [these facts], do you think that's an adequate strategy? Or do you think that should be reconsidered and maybe we need to call [women] back in and rescreen these folks?"
McClelland's answer might surprise you.
"We're not at a stage where we can tell women that they need to come back in to make sure that the BV is gone," he said. "If they don't have symptoms from a clinical perspective, I think we're done."
But, he added, if funding and research continues on the interplay between the microbiome with the immune system, that could change.
"I would love at some point in my career," he said, "to be able to say that we need to control asymptomatic BV."
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.
This article was provided by TheBodyPRO. It is a part of the publication The 24th Conference on Retroviruses and Opportunistic Infections.
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