Scientists trying to put HIV-prevention methods in the hands of women have been disappointed so far in their efforts with vaginal microbicides. In the lab, in vitro testing of microbicides like nonoxynol-9, and cellulose sulfate have produced promising results, but when subjected to clinical trials, each of these compounds has failed miserably. Not only do nonoxynol-9, and cellulose sulfate fail to protect against HIV infection, when a woman uses the stuff frequently she actually has an increased risk of HIV infection.
Why the tragic paradox? Do microbicides like these change the vaginal microbiome? The authors of a paper in mBio this week tested whether products like these might impact the the microbial community of the vagina, an observation that might begin to explain why these microbicides don’t work on HIV in real-world conditions.
The researchers assigned 13 test subjects to use a cellulose sulfate product twice daily for almost two weeks, 12 subjects to use nonoxynol-9, and 10 control subjects to use a placebo. With a total of 146 samples from these subjects and controls, they extracted the sample DNA and amplified selected, bar-coded regions of the 16SrRNA genes. After pyrosequencing these fragments, they were able to identify 296 different taxa among all samples.
Their results show the microbicides have dramatic effects on the residents of the vagina: after seven days of use, among other notable changes, most communities shifted from a composition dominated by by species of Lactobacillus to “community states mainly dominated by anaerobes and by members of the genera Streptococcus, Enterococcus, and Escherichia.”
From a strictly ecological point of view, a big genus swing like that can’t be good. But the results also offer a plausible reason for microbicide failure. The authors propose that distorting the microbiota could conceivably increase levels of inflammatory cytokines, which would activate potential host cells for HIV. This could increase overall transmission rates, they say, which could explain why nonoxynol-9 and cellulose sulfate make HIV matters worse for women.
Moving forward, the authors make some concrete recommendations for HIV transmission interventions. First, considering the failure of previous microbicides during clinical trials, they recommend conducting molecular, culture-independent evaluations like those described in this study early on in clinical assessment of candidate microbicides. Better to know before the real-world trial whether a microbicide might actually worsen a woman’s risk of HIV infection. Seems like the only ethical thing to do.
The authors also point out that HIV microbicides could work better if they worked with the vaginal microbiome and not against it. Components that help promote or maintain a healthy, Lactobacillus-dominated vaginal community could boost the effectiveness of an agent that targets the virus, they say, while preventing the kind of failures suffered by earlier formulations.