Topical Dapivirine Effective, Even in Women With Vaginosis

Heather Boerner

August 01, 2017

PARIS — Dapivirine does not seem to be affected by microbes associated with bacterial vaginosis, new research shows, suggesting that the dapivirine ring could be a viable option for HIV prevention in women.

"The good news is that the dapivirine ring should work in women regardless of the type of vaginal microbiome they have," said Sharon Hillier, PhD, from the University of Pittsburgh.

"If Gardnerella had undermined the effective concentrations of the drug, I think it would have further dampened enthusiasm" for the use of dapivirine in the prevention of HIV, she told Medscape Medical News here at the International AIDS Society (IAS) 2017 Conference.

At the IAS meeting last year, researchers presented data showing that tenofovir — one of the drugs in Truvada, the oral pre-exposure prophylaxis developed by Gilead Science — is absorbed quickly when a woman's microbiome is not dominated by so-called protective Lactobacillus, as reported by Medscape Medical News.

This suggested that the effectiveness of tenofovir could vary in different vaginal microbiomes.

Another study presented at IAS 2016 — by Salim Abdool Karim, PhD, from the Centre for the AIDS Programme of Research in South Africa — showed that when G vaginalis is present in a woman's microbiome, levels of tenofovir drop to zero within 24 hours of gel application.

Dr Hillier's team wondered if the same thing might happen with dapivirine. In their 7-day study, the researchers assessed the impact of vaginal microbiota on dapivirine levels in 66 women without HIV, Chlamydia, gonorrhea, or trichomoniasis who were on contraception.

On day 1, each woman inserted dapivirine 1.25 mg — gel or film formulation — into her vagina under direct observation. On days 2 to 6, the women were asked to apply the gel or film themselves at home.

On day 7, the women returned to the clinic, where trough drug levels, drug plasma, and vaginal fluids were assessed, and they then applied their final dose under direct observation. Two hours later, after the drug had a chance to reach peak levels, another plasma sample was taken and a cervical biopsy performed.

Microbial communities — in particular, Gardnerella vaginalis, which is associated with bacterial vaginosis, and Lactobacillus crispatus, L jensenii, and L gasseri, theso-called beneficial bacteria — were assessed with quantitative PCR. Then a Nugget Score was used to determine whether or not the women had bacterial vaginosis.

"For those of you who don't think about vaginal microbiome all the time," said Dr Hillier, we were really testing whether specific microbiomes in individual women affected the level of dapivirine that "infiltrated the genital epithelium and then the plasma."

The team found that there was "absolutely no association" between dapivirine levels and G vaginalis. And when they looked at drug concentrations in cervical tissue — a key marker of protection — levels of dapivirine remained consistent.

"There was a slight trend toward higher efficacy in those with bacterial vaginosis," Dr Hillier reported, "but that was nonsignificant."

Ring Safety

The vaginal ring loaded with dapivirine is safe and acceptable, according to a phase 2a randomized, double-blind, placebo-controlled study of 96 American adolescents presented at the meeting this year.

In addition, the ring was shown to reduce the risk for HIV by 56% in a previous randomized controlled trial, as reported by Medscape Medical News. Follow-up studies, especially in young women at the highest risk for HIV, are still underway.

International Partnership for Microbicides, which developed the dapivirine ring, has applied to bring the ring to market in Europe. In the United States, however, the National Institutes of Health is in the process of crafting a new HIV prevention strategy, and topical agents like dapivirine might be left out of funding goals.

Although these data are preliminary and the sample size was small, they are "encouraging," said Jennifer Balkus, MD, from the University of Washington in Seattle.

It is not clear if there is a way to make up for the effect of Gardnerella on tenofovir gel. However, a vaginal ring that contains tenofovir and levonorgestrel is being developed by CONRAD, a nonprofit reproductive health organization, she reported.

It is possible that tenofovir could be a viable option "as long as there is enough drug in place to overcome the inhibition," she told Medscape Medical News.

Still, if these dapivirine data are confirmed, providers "wouldn't necessarily have to take into account whether a patient has bacterial vaginosis when prescribing the ring," Dr Balkus said. "Then they can treat bacterial vaginosis as its own clinical condition."

This study was funded by the National Institutes of Health. The International Partnership for Microbicides donated dapivirine for the study, and CONRAD donated tenofovir. Dr Hillier, Dr Ravel, and Dr Balkus have disclosed no relevant financial relationships.

International AIDS Society (IAS) 2017 Conference: Abstract TUAC0104. Presented July 25, 2017.

Follow Medscape on Twitter @Medscape and Heather Boerner @HeatherBoerner

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