Vaginal Microbiota Can Affect HIV PrEP Drug Metabolism

By Anne Harding

December 29, 2020

NEW YORK (Reuters Health) - Vaginal microbes associated with bacterial vaginosis (BV) metabolize drugs used in HIV pre-exposure prophylaxis (PrEP) at different rates, which could explain why PrEP is less effective in women than in men, new findings suggest.

"Drugs can be differentially metabolized by bacteria, and that's something that needs to be considered in terms of efficacy," Dr. Nichole R. Klatt of the University of Washington in Seattle told Reuters Health by phone. "We really need to better understand bacterial vaginosis and come up with better interventions."

From 40% to 60% of women have BV, which recurs after treatment within the month in 50% of patients and within the year in 90%, Dr. Klatt noted.

While antiretroviral PrEP is highly effective in men, studies have found big reductions in efficacy among women, she added. "It was mostly blamed on adherence."

In a study published in Science in 2017, Dr. Klatt and her team found that tenofovir (TFV) gel was less effective for preventing HIV in women with vaginal microbiomes dominated by non-Lactobacillus bacteria, who had an 18% reduction in HIV incidence, compared to a 61% reduction in women with Lactobacillus-predominant microbiomes (https://bit.ly/371dFkh).

In the current study, published in PLOS Pathogens, they conducted several in vitro and ex vivo studies using cervicovaginal lavage (CVL) samples from 44 women, 15 of whom had BV. As in the 2017 study, they identified two predominant types of bacterial community, with 18 women having more than 50% Lactobacillus and 26 having non-Lactobacillus dominant microbiomes.

Rates of dapavirine (DPV) and TFV degradation were negatively associated with the abundance of Lactobacillus in CVL samples (both P<0.0001), but tenofovir alafenamide (TAF) degradation rate was not.

After incubation with TFV for 24 hours, 79.6% of the drug remained in the Lactobacillus-dominant samples, on average, versus 43.8% for the non-Lactobacillus samples. For DPV, the amount of drug remaining was 73.2% with the Lactobacillus-dominant samples and 38.8% in the non-Lactobacillus dominant samples.

"We found that TAF wasn't degraded virtually at all, so that means that may be a better candidate for PrEP in women," Dr. Klatt said. However, she added, TAF has not been approved for women by the U.S. Food and Drug Administration. "It's very difficult for women to have access to that even though it is probably a superior drug," she said.

New PrEP therapies, including injectable formulations given every three months, are currently in clinical trials, Dr. Klatt noted. "I really hope these trials are more focused on women, because the research community has really dropped the ball on it in the past."

The study did not have commercial funding.

SOURCE: https://bit.ly/2VQLBJI PLOS Pathogens, online December 3, 2020.

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