The composition of the vaginal microbiome of a woman greatly influences its susceptibility to HIV infection, suggest studies presented Durban, South Africa, today to kick off the 21st international AIDS Conference a week. Microbiome may also explain why pre-exposure prophylaxis (PrEP) -Give HIV drugs to prevent infection, works better in men than in women. These results are of particular importance here in the KwaZulu-Natal province in South Africa, which has high perplexingly levels of HIV infection among adolescents and young women.
At a press conference today, two related studies have been reported that researchers will report on Tuesday. "It's a great story, and it's a really important insight as to why young women in Africa are infected at high rates," said Douglas Kwon, an immunologist at Massachusetts General Hospital in Boston, who was not involved in the work, but studied vaginal microbiome and HIV.
new results come all the women followed studies that have participated in a PrEP study of a vaginal gel containing the drug tenofovir anti- HIV. Led by the Centre for the AIDS Programme of research in South Africa (CAPRISA) based in Durban, the trial took place in a region where 66% of 30 year-old women are infected. the team did CAPRISA headlines in 2010 when he showed that the gel reduced the risk of infection of a woman of 44%. But this encouraging result was, he also raised questions about why the gel did not was more effective, and it does not indeed in a subsequent trial.
The most provocative of the two new studies have carefully analyzed the vaginal microflora 119 women who were HIV-negative at the start of the trial and compared the 49 who were infected with the others. In a previous study of women in this trial, the CAPRISA researchers and their collaborators at the University of Cape Town in South Africa said last year that women who had increased inflammation of the genital tract were more likely infection. Monkey studies have suggested a mechanism: inflammation brings more of the HIV favorite target, CD4 white blood cells to the mucosal surface. And in a separate study of women in KwaZulu-Natal, Kwon and colleagues reported last year that inflammation in the vagina is associated with a reduction of Lactobacillus , a famous case-in yogurt creates an inhospitable acidic environment for many pathogens. As the researchers noted, but could not explain, Lactobacillus dominated in the vaginas of only 37% of the women they studied, compared with 0% of white women in the US
. So far, however, no one had clearly linked vaginal microbiomes specific to an increased risk of HIV infection. "Now we have real data," says the director of CAPRISA epidemiologist Salim Abdool Karim.
The data comes from a massive effort to identify the bacterial species on vaginal smears of women in the study tenofovir gel CAPRISA. Ian Lipkin's lab at Columbia University, who specializes in search of rare pathogens extract about 25,000 bacterial ribosomal RNA sequences of the swab and used genomic data to identify a total 1368 species.
A relatively rare species, Prevotella bivia stood out as particularly dangerous. women whose vaginal microbiome included more than 1% of P . bivia had the highest levels of genital inflammation and the highest probability of being infected by HIV. These women have significantly reduced levels of Lactobacillus and researchers showed that P . bivia was associated with high levels of a compound of inflammation promoting called lipopolysaccharide (LPS). Earlier in vitro studies have shown that P . bivia growth leads to high levels of LPS, which constitute the cell wall of bacteria, LPS and, in turn, stimulates the production of inflammatory chemical messengers.
Women who had more than 1% P . bivia were almost 13 times more likely to be infected with HIV.
In the second study, vaginal washes of 688 women in the same trial CAPRISA, Adam Burgener Agency of Canada Public Health in Winnipeg and Nichole Klatt from the University of Washington, Seattle, showed that the vaginal microbiome does not only influence the risk of infection; it can also interfere directly with PrEP. In women with microbiome contained less than 50% lactobacilli , tenofovir gel protected only 18% of women who received it. The efficiency jumped to 61% when the proportion of Lactobacillus species was greater than 50%. And when the researchers mixed with various bacteria tenofovir in the laboratory, they found that the drug concentrations remained high in the presence of lactobacilli but halved when mixed with bacteria called Gardnerella , which blooms when lactobacilli are rare. " Gardnerella gobbles up," says Karim.
Anthony Fauci, director of the National Institute of Allergy and Infectious Diseases in Bethesda, Maryland USA, said these results open the ability to manipulate the vaginal microbiome to help guide HIV infections among vulnerable young women. antibiotics, for example, could strike back Gardnerella or Prevotella . or introduce beneficial bacteria, called probiotics, bacteria could "crowd out" dangerous. "When I saw this data, I thought if it pans, it is a means of relatively low technology to have a impact on whether you are infected or not, "Fauci said.
Kwon warned that efforts to manipulate the microbiome to treat inflammatory bowel disease have had limited success. "We know that bowel manipulation of these communities is often extremely difficult," he said. "There are many home mechanisms to maintain these communities."
But Fauci is optimistic . the vaginal vault tissue less sensitive than the gut, he said. "You're talking inches rather than feet," he said. "This is an interesting question that needs to be pursued."
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