Bacterial vaginosis unlikely to reduce anti-HIV efficacy of oral tenofovir PrEP

By Joan Stephenson

NEW YORK (Reuters Health) - The efficacy of oral tenofovir-based pre-exposure prophylaxis (PrEP) for HIV infection among African women with bacterial vaginosis (BV) is similar to that among those with healthy vaginal microbiota, new research shows.

“These are the first findings of oral PrEP and BV, and they are reassuring that women with BV can use oral PrEP and receive the same benefit as women without BV,” lead author Dr. Renee Heffron, of the University of Washington, Seattle, told Reuters Health by email.

Previous research had shown that a daily regimen of oral tenofovir-based PrEP offers more than 90% protection among individuals with high adherence. However, some data “suggested that certain bacteria common among women with BV could alter the efficacy of tenofovir gel, a different product that has been tested in trials of HIV prevention for women,” Dr. Heffron explained.

Findings from a clinical trial of nearly 700 women, reported by Klatt and colleagues in Science earlier this year (http://bit.ly/2uC156d), found that topical PrEP in the form of a tenofovir gel was three times more effective among those with a Lactobacillus-dominant vaginal microbiome than among other women.

The Science study also found that the bacterium Gardnerella vaginalis tended to predominate in the women for whom tenofovir was less effective, and that this microbe could rapidly metabolize and inactivate the drug.

To investigate whether they would see a similar effect of vaginal microbiota for oral PrEP, Dr. Heffron and her colleagues analyzed prospectively collected data from 1470 HIV-uninfected women (median age, 33) who had participated in the Partners PrEP Study.

That randomized trial examined how well daily oral tenofovir, alone or combined with emtricitabine, compared with placebo in HIV-serodiscordant couples in Kenya and Uganda. The aim was to assess the effectiveness of PrEP in preventing HIV in the uninfected partner.

An “optimal” vaginal microbiome is one in which Lactobacillus predominates and Gardnerella and Bacteroides bacteria are absent; non-Lactobacillus bacteria such as G. vaginalis predominate in “suboptimal” vaginal microbiota. Prospective cohort studies have shown that BV increases a woman’s risk of acquiring HIV.

In the Partners PrEP study, BV status had been determined by yearly microscopy and Nugent scoring (a Gram-stain scoring system that reflects, in part, the presence or absence of Lactobacillus, G. vaginalis, and Bacteroides).

In the new study, Heffron and colleagues used Cox proportional hazards regression analysis to assess PrEP efficacy for women with healthy microbiota (Nugent scores of 0 to 3), intermediate microbiota (scores 4 to 6), or bacterial vaginosis (scores 7 to 10). The report was published in Lancet HIV, online July 18.

At enrollment, 357 women (24%) had bacterial vaginosis by Gram-stain criteria, and 37% had Gardnerella vaginalis or Bacteroides.

Forty-five women seroconverted to HIV. PrEP efficacy did not differ significantly between women with healthy versus abnormal microbiota.

HIV incidence, per 100 person-years, was 0.6 and 2.5 in the PrEP group and placebo groups, respectively, among women with healthy microbiota (77% efficacy of PrEP); 1.8 vs. 3.5 among women with intermediate microbiota (63% efficacy); and 0.9 vs. 3.5 among women with BV (73% efficacy).

A separate efficacy analysis showed that PrEP efficacy did not differ significantly according to a woman’s Nugent score.

“The data reported by Heffron and colleagues are reassuring in that they show that oral tenofovir disoproxil fumarate PrEP can be highly efficacious against HIV in women, even in the context of vaginal dysbiosis, when adherence is high,” Dr. Janneke van de Wijgert, of University Medical Center Utrecht, Netherlands, and Dr. Sheena McCormack, of the University of Liverpool, UK, note in an accompanying commentary.

“We strongly believe that roll-out of tenofovir disoproxil fumarate oral PrEP should continue in communities with a high burden of HIV and vaginal dysbiosis, and that vaginal PrEP should continue to be developed,” they write.

Dr. Douglas Kwon, of Massachusetts General Hospital in Boston, who studies the effect of HIV infection on mucosal tissues, told Reuters Health by email that the new findings, suggesting that vaginal bacteria do not affect how well oral forms of PrEP work, are important in light of the earlier findings by Klatt and colleagues that certain types of microbial communities reduce the efficacy of tenofovir gel PrEP.

“The reasons why there is a different effect of vaginal bacteria on oral tenofovir vs. topical tenofovir for HIV prevention remain unclear,” noted Dr. Kwon, who was not involved with the current study. “It may be due to the route of administration or the differences in baseline efficacy of the two forms of PrEP.”

He is interested to learn whether vaginal bacteria affect other approaches to preventing HIV acquisition, such as upcoming HIV vaccines, drug implants, or long-lasting injections.

SOURCE: http://bit.ly/2eLVGWj and http://bit.ly/2h3pGhb

Lancet HIV 2017.

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