Gardnerella vaginalis affects HIV drug efficacy Dennis Kunzel Microscopy/SPL

The balance of bacterial strains living in the vagina can influence how effective a medicated gel is at protecting against HIV. The finding may explain why women need to take PrEP treatments more regularly than men to be protected against contracting the virus.

The drug tenofovir is a mainstay of HIV treatment and prevention. When taken orally, it protects well against HIV infection, but researchers have wondered why it doesn’t work as well when applied as a microbicidal gel in the vagina. Some have suggested this is because the women taking part in tests of the gel didn’t use it reliably, but now it looks like vaginal microbes might bear part of the blame.

The vaginas of healthy women are known to be dominated by Lactobacillus bacteria. Having a more diverse collection of bacteria has been linked to an increased likelihood of urinary tract infections, while the presence of particular species, such as Gardnerella vaginalis, is linked to bacterial vaginosis, a poorly understood condition that causes abnormal discharge and odour.


Now Nichole Klatt at the University of Washington, Seattle, and her colleagues have found that the types of microorganisms living in the vagina are linked to how effective tenofovir gel is at protecting against HIV infection.

“It’s a really serious effect,” says Klatt, whose team made this discovery by analysing samples taken during a clinical trial. “We went from 60 per cent protection if you have good Lactobacillus to 18 per cent – really no protection at all – if you have bad bacteria.”

Less protected

G. vaginalis seems to be the main culprit. The team found that this species takes up tenofovir and chemically processes it at high rates, stopping the drug from entering the cells it is intended to protect. Other types of bacteria can do this too, but they aren’t as efficient so don’t pose the same danger.

“This is an interesting and exciting finding,” says Sharon Hillier at the University of Pittsburgh. “To me, it means that tenofovir dosing is less forgiving of a missed dose if you have bacterial vaginosis.”

The finding raises the question of whether the microbiome may help explain the different protective effects of oral PrEP, a preventative HIV procedure, in men and women. Men can skip the pill for a day or two, but to be protected, women are less likely to get away with missing a day’s pill.

It was thought that this difference may be due to differences in the tissues involved in vaginal and anal sex, but now it seems that may not be the whole story. There are a lot of reasons to think bacterial vaginosis could be affecting vaginal protection from oral PrEP, says Klatt.

Balancing bacteria

Douglas Kwon, at the Ragon Institute in Boston, believes Klatt’s findings may be important when protective measures are only partially effective. “By targeting the microbiome, you may be able to make it more efficacious,” he says. While oral PrEP already works very well, the microbiome may be more of a problem when using protective gels.

Bacterial vaginosis is the most common infection in women between the ages of 15 and 44. While antibiotics can be used to treat bacterial vaginosis, it recurs within a year in around 60 per cent of cases in the US, and at even higher rates in developing nations where HIV is most common.

Nevertheless, Klatt is hopeful that antibiotics can be used to knock out bad players in the vaginal microbiome. Other researchers are developing a product that may be able to re-establish and maintain a healthy Lactobacillus-based microbiome, to boost protection against HIV and other sexually transmitted infections.

Journal reference: Science, DOI: 10.1126/science.aai9383

Read more: Unprotected sex may disrupt the microbiome in vagina