Adam Burgener, PhD, is current head of proteomics at the National HIV and Retrovirology Labs at the Public Health Agency of Canada, and an associate professor at University of Manitoba (UM). His recent research has focused on understanding the role of host-microbial factors at mucosal surfaces in HIV transmission and pathogenesis. His team reported that the microbiome can affect antiretroviral-based preexposure prophylaxis for HIV prevention in women. During IAS 2019, a member of his group presented preliminary results showing a role for the vaginal microbiome in the link between hormonal contraceptives and HIV acquisition risk and genital inflammation.
Univadis sat down with Dr. Burgener to discuss why the vaginal microbiome should be considered when evaluating hormonal contraceptive safety or other products that can influence vaginal health.
This interview has been edited for clarity and length.
UNIVADIS: If I ask you to pick 3 highlights in the understanding of microbiome dysbiosis and translocation, 2 of them important factors in pathogenesis, what would you choose?
DR. BURGENER: The focus of our research is the vaginal microbiome and how it relates to HIV transmission in women. The 3 major points or highlights are [as follows]: (i) the microbiome is very important for the host immune system and resistance to infectious diseases; (ii) dysbiosis of the microbiome makes us more susceptible to disease; and (iii) the vaginal microbiome is very critical to HIV transmission risk in women.
Injectable hormonal contraceptives have been hypothesized to be linked to increased risk for HIV. The ECHO trial is showing limited differences between injectable hormonal contraceptives and copper IUD in the comparison groups. The hypothesized mechanism was that contraceptives change the microbiome, perhaps causing some inflammatory bacteria to appear and increasing risk.
Since your microbiome sets the stage for the inflammation state in the female genital tract, we asked the opposite question: do women with different microbiomes respond differently to contraceptives? Everybody is different, and your gut microbiome determines whether certain drugs work for you and how you respond to therapy, so it is not far-fetched to think that your vaginal microbiome can impact how hormonal contraceptives will affect local immunity.
So, we looked at women in 2 broad categories: women who have vaginal Lactobacillus and low inflammation and women who do not have vaginal Lactobacillus and have high inflammation. This was a substudy within the CAPRISA 004 trial.
What we found is that in women with vaginal Lactobacillus, there is a large change in mucosal inflammation associated with serum hormone levels of the injectable contraceptive DMPA [depot medroxyprogesterone acetate], but this was not observed, at least using our techniques, in women who did not have vaginal Lactobacillus and had bacterial vaginosis. [These results suggest] women may respond differently based on their microbiome profiles.
UNIVADIS: But how do you explain these results? If women with Lactobacillus-dominant populations have less inflammation than those with a non-Lactobacillus vaginal-dominant community, how is it that you see now more inflammation in women with Lactobacillus? Is the hormonal contraceptive changing something?
DR. BURGENER: It is possible that DMPA is causing inflammation, whether it is changing Lactobacillus in terms of what they are doing [or affecting] host inflammation pathways in the vaginal mucosa.
We looked at changes in the functional pathways within the bacteria, but there wasn’t really that much going on. But looking at the host inflammation pathways in the vaginal mucosa, there were moderate changes in the host immune profile. A lot of these pathways have been related in the literature to progesterone levels.
We think DMPA is causing cascades of inflammation from the host, which are only observable or more observable in women who have low baseline inflammation to start with—women with the Lactobacillus-dominant microbiome.
But it is also possible that DMPA is changing the function of the bacteria in some way. However, at least with RNA analysis, we could not find any changes in the abundance of molecules or their functionalities at all.
UNIVADIS: Changing our microbiome might be difficult, but maybe it would be easier to find molecules associated with functions we could target directly?
DR. BURGENER: I think understanding function and how this might be important for therapy is really important. Right now, [we are] shooting from the hip in terms of what type of probiotic strategy might be helpful to promote strains that have properties believed to be beneficial for colonization. But no one really knows what is important for durability of vaginal Lactobacillus and what is important for long-term colonization.
So, we are studying the function of the microbiome to identify features, behaviors of the microbes in women that have high stability vs women that have high variability. [We want] to see what functions are different and if we can identify functions that we can say "this functional feature is very important for stability." Then, we could use that as a roadmap or a guide to select bacterial strains with certain metabolic properties or a strain that is a probiotic. [We can] use what we study from humans to inform how to develop better technologies for Lactobacillus.
That’s the goal with our trial study. Kind of outside this scope of HIV, it is very important because we need more fundamental research if we are going to get an intervention that works properly.