Meet the female powerhouses behind HIV research at Burnet
Professor Gilda Tachedjian, Dr Lindi Masson and Dr Anna Hearps are at the vanguard of HIV research aiming to help women better protect themselves against the disease.
Globally, almost three out of five young people who became infected with HIV in 2021 were adolescent girls and young women.
Physiologically, the larger surface area of the vagina makes women especially susceptible to HIV, and there are many other factors at play including:
social issues like power and equity in relationships which may mean women can’t always negotiate condom use;
trauma during sexual activity which can damage the epithelial barrier in the genital tract making women more susceptible to infection;
and high rates of sexually transmitted infections (STIs) and bacterial vaginosis (BV) in some populations, which causes inflammation in the genital tract, again increasing the risk of acquiring HIV.
All of these factors can be compounded by late diagnosis, and inequitable access to education and treatment.
Women living with HIV tend to be neglected, said Professor Gilda Tachedjian, Burnet Institute’s Head of Life Sciences.
“Particularly in Australia, it's considered a disease or infection that predominantly affects men who have sex with men,” she said.
And while we need to acknowledge we’ve come a long way with HIV – consider for example the progress made with HIV pre-exposure prophylaxis (PrEP) – we also need to shine a light on women, Professor Tachedjian said.
In 2021, 49 per cent of all new HIV infections around the world – some 1.5 million new infections in total – were in women and girls.
In sub-Saharan Africa, this figure is 63 per cent.
In Australia, just under 40 per cent of new HIV infections attributed to heterosexual sex are in women.
“Around two-thirds of these new infections were in women born overseas,” Professor Tachedjian said.
If we going to meet our goal of driving down new HIV infections, we really need to target these key populations, she said.
Read on to find out how Burnet researchers Professor Tachedjian, Dr Lindi Masson and Dr Anna Hearps are working to better protect women against HIV.
“Women who've got an optimal, Lactobacillus-dominated [vaginal microbiome], they're less likely to get HIV,” Professor Tachedjian said.
An optimal vaginal microbiota is one that’s dominated by Lactobacillus species, which produce the metabolite lactic acid.
“Lactic acid reduces the pH in the vagina, which is antimicrobial,” Professor Tachedjian said. “We’ve done studies showing that in the lab, lactic acid is really potent for killing HIV at low pH.”
Professor Tachedjian and her team have also looked at the anti-inflammatory effects of lactic acid.
“Your vagina is covered with these epithelial cells, and the microbiota sit on there,” she said.
Lactic acid has an anti-inflammatory effect on epithelial cells, which decreases your HIV risk.
It also strengthens the junctions between these cells, preventing harmful bacteria and viruses, including HIV, from getting into the body.
I've been fascinated about how an optimal vaginal microbiota is protective,” Professor Tachedjian said.
“They're protected to some extent against HIV infection and also other STIs, and then more broadly adverse reproductive health outcomes as well, like preterm birth.”
Professor Tachedjian’s team is now using these findings to formulate and test vaginal gels that slowly release lactic acid.
They hope ultimately these could be used by women, for example with BV, to shift their vaginal microbiome to a more optimal state with all the protective benefits that offers.
Such an intervention could also help increase the effectiveness of HIV antivirals, as other studies have found that the vaginal microbiome can influence the efficacy of topical PrEP.
“If women have inflammation in their genital tracts then they're at very high risk of HIV acquisition,” Dr Lindi Masson said.
It was during her PhD at the University of Cape Town that Burnet Senior Research Fellow Dr Lindi Masson made the link between inflammation in the genital tract and women having a very high risk of HIV acquisition.
She and her colleagues wanted to understand what was causing this inflammation in African women.
“What we found in our earlier studies was that the majority of cases of inflammation are caused by STIs and BV,” she said.
In some of the communities Dr Masson studied, over 70 per cent of the women had either an STI or BV.
In South Africa and other-resource-limited settings, STIs and BV are only treated if women have symptoms and they go to a clinic looking for care. But most of these women are asymptomatic and still have high levels of inflammation and HIV risk.
We wanted a way to try and pick up more of these asymptomatic infections, and to do that we needed to develop an inexpensive, true point-of-care approach,” Dr Masson said.
Dr Masson and her colleagues at the University of Cape Town looked for the best inflammatory biomarkers of STIs and BV, and validated three different markers they found in subsequent cohort studies.
“Since then, we’ve been developing a point-of-care test to measure these biomarkers,” she said.
The test requires a vaginal swab which can be self-collected, it’s eluted in a buffer and then applied to a testing cartridge, similar to what you do with a COVID-19 rapid antigen test.
Currently the team is optimising a second prototype, with the aim that it will be made available free of charge to women attending public clinics.
When they come in for their contraception or for other reasons, they could also have this test to check for genital inflammation, Dr Masson said.
If the test is positive, patient management will depend on the resources available and the implementation plan that is currently being developed through stakeholder and end user consultation.
Dr Masson has also been working on a live biotherapeutics project which has similar goals to Professor Tachedjian’s lactic acid project, except this time using actual Lactobacillus bacteria rather than the metabolite.
“The aim would be to develop a product that you can apply topically,” she said.
"Basically, what we want to do is try and recolonise the vagina with healthy bacteria that protect against BV, protect against STIs including HIV, and protect against adverse birth outcomes.”
Most of the vaginal probiotics that are already available don’t include the species of Lactobacillus that you actually find in the vagina.
“They’ve been developed using gut Lactobacillus which doesn’t make any sense, obviously they’re not going to stick around,” Dr Masson said.
Lactobacillus bacteria also vary by geographical region and ethnicity, so existing products that have been developed for US or European women, wouldn’t necessarily be suitable for African women.
Our amazing team of women @UCTIDM @BurnetInstitute leading the development of the @GIFT_for_Africa test to improve women's sexual and reproductive health #WomenInScience @MucosalGroup pic.twitter.com/IWcT16yAMC— Lindi Masson (@LindiMasson) November 12, 2022
Dr Masson and her colleagues have been isolating Lactobacillus bacteria from South African women, and characterising their properties to identify ones that produce lactic acid and have other protective properties.
The next step is to try to scale that up and develop them into live biotherapeutic products.
“The hope ultimately would be that you wouldn’t have to keep applying it,” Dr Masson said.
“You hopefully put the bacteria in and if they have all the right factors to colonise, then they stay.”
"The persistence of HIV within cells in this silent state is one of the biggest barriers to HIV cure," Dr Anna Hearps said.
Sleeping or silent HIV is virus that isn’t replicating but also which can’t be seen by the immune system, and hence it doesn’t know that it’s there to eliminate.
Dr Hearps’ work focuses on macrophages, a type of immune cell that resides in tissues throughout the body.
“They’re really important immune cells – we call them the vacuum cleaners of the immune system – one of their roles is to gobble up and eliminate bacteria or dead and dying cells,” she said.
Macrophages also orchestrate the immune response to a particular pathogen.
While HIV predominantly affects T cells which are in blood, it can also infect macrophages.
“We know that they are infected by HIV, and that they do persist in people with HIV who are on antiretroviral therapy,” Dr Hearps said.
While the reservoir of silent or sleeping HIV in macrophages will be less than the reservoir in T cells, even one copy of HIV in the body can lead to the virus bouncing back when someone stops therapy, Dr Hearps said.
So, if an HIV cure is going to be successful, we need to target all of the residual HIV, and some of that lies within macrophages,” she said.
Our only options are to either wake up and then get rid of the sleeping HIV, or keep it asleep permanently.
Dr Hearps and her colleagues are exploring both options.
“We’ve set up an in vitro system where we take immune cells that are in the blood, and we turn them into macrophages in the lab, and then we infect them with HIV,” she said.
They’re then using this model to help identify drugs which are good at waking up sleeping HIV in macrophages, or keeping it asleep.
Dr Anna Hearps tells @livingposvic #WorldAIDSDay launch about some of the barriers to her research into the impact of #HIV on the immune system: "With regard to how we're going with the meaningful participation (of women) I am going to answer very honestly and say, 'terribly' ... pic.twitter.com/YdNdjJgFuH— Burnet Institute (@BurnetInstitute) December 1, 2022
They’re also using a sequencing technique called RNA-Seq which allows them to look at all the genes being expressed in one of the cells that is silently infected with HIV.
“Only a very small proportion of cells are silently infected with HIV, it's a real needle in a haystack situation,” Dr Hearps said.
“You can pick up the one that’s got the silent HIV and say ‘Well, how’s that one different to the other one?’”
The third part of their project is identifying strategies for how to kill those macrophages infected with silent HIV.
One way might be through using antibodies which bind to the HIV proteins on the cell and flag it for the immune system’s natural killer cells to eliminate.
“We're profiling the cells that actually are good at recognising and killing HIV-infected macrophages,” Dr Hearps said.
“Then trying to figure out how could we either expand them within a person … or ideally have an off-the-shelf product, because the thing with natural killer cells is they don't have to necessarily be your own cells.
The other half of Dr Hearps’ HIV research looks at comorbidities.
"If you put people on therapy you can protect them from AIDS-related diseases but they are at an increased risk of age-related conditions,” Dr Hearps said.
These include frailty, neurocognitive impairment, cardiovascular disease, cancers – all these other diseases which are age-related.
“We don't really understand why, except that we know that HIV can cause a lot of collateral damage to the immune system, which may drive immune aging.”
Dr Hearps and her colleagues are trying to understand what the mechanisms are that are driving, for example, increased cardiovascular disease in people with HIV.
“All the traditional risk factors that drive cardiovascular disease in the general population, also apply to people with HIV. But there's additional things that HIV is bringing in,” she said.
And it appears that these impacts vary by sex.
“A couple of studies have shown that some parameters of cardiovascular disease in HIV positive women, are actually worse than what you will see in HIV positive men,” Dr Hearps said.
But work in this area also reveals a huge gap in our research.
“All of the work that we do here, in cohorts in Australia, it's all men … because the HIV positive population in Australia largely was and still is, men who have sex with men,” Dr Hearps said.
“We just cannot recruit sufficient women to get meaningful data.”
This means HIV comorbidity studies have not been done in women to the same extent as they’ve been done in men.
“Here within Australia we’ve failed really to include women in our research, and that’s because it’s incredibly difficult. But just because it’s hard doesn’t mean you don’t do it,” Dr Hearps said.
Going forward researchers need to consider how we engage women in HIV research and better understand what are the barriers to them participating, she said.
“It will be very difficult to achieve parity in Australia because of the demographics of the population, but our studies should, at the very least, represent the population.”
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