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New hope in AIDS research

July 18, 2019 — 

For over three decades, HIV has infected an ever-growing number of people, but two newly funded University of Manitoba research projects offer promising hope to change the disease’s course.

The Canadian Institutes of Health Research (CIHR) has provided significant funding to two Rady Faculty of Health Sciences professors: Medical microbiologist Keith Fowke and his team will receive $2 million dollars over five years to investigate how anti-retroviral and anti-inflammatory medications can prevent new HIV infections; and Obstetrics and Gynecology professor Adam Burgener and his team will receive $2 million dollars over five years to investigate how the microbiome in the human body interacts with vaccines and anti-retroviral drugs against HIV.

“I congratulate Drs. Fowke and Burgener on their success in this competitive funding award,” said Digvir Jayas, vice-president (research and international) and Distinguished Professor at the U of M. “Their teams are made up of national and international experts who I have no doubt will make inroads in their investigations, for the benefit of all.”

On July 17, the Honourable Ginette Petitpas Taylor, Canada’s Minister of Health, announced an investment of more than $32 million in sexually transmitted and blood-borne infections research from the Government of Canada, through the Canadian Institutes of Health Research (CIHR).

The University of Manitoba has long been at the forefront of HIV/AIDS research, running a collaboration with the University of Nairobi since 1980, significantly advancing the world’s understanding of HIV/AIDS with monumental discoveries such as the virus being transmitted through heterosexual partnerships and from mother to child through breast milk; they also discovered a group of sex workers seemingly immune to the virus, to name just three discoveries.

Fowke’s [BSc(Hons)/88, PhD/95] and Burgener’s [BSc(Hons)/99, PhD/05] new projects continue to uphold this established track record.

 

Fowke’s project: Combination HIV Prevention: Using anti-retroviral and anti-inflammatory medications to prevent new HIV infections

Co-Principle investigators: Emmanuel Ho (University of Waterloo); Joshua Kimani (Medical Microbiology and Infectious Diseases (MMID – U of M and University of Nairobi); Lyle Mckinnon (MMID-UM); Thomas Murooka (Department of Immunology-UM); Julie Lajoie (MMID-UM); Julius Oyugi (MMID and University of Nairobi)

Just as cancer therapy attacks with multiple drugs, this team will employ a combination of biomedical approaches that blocks HIV infections in different ways.

Firstly, they will use anti-HIV drugs that work by blocking the ability of the virus to replicate. Secondly, they will block the inflammatory process that brings the cells that HIV primarily infects into the genital tract using anti-inflammatory drugs. Based on research pioneered by their team members, they have shown that inflammation greatly increases the risk of HIV transmission and can actually nullify the effects of anti-HIV drugs to prevent infections. In one of their pilot studies, for instance, they showed that the anti-inflammatory drug aspirin (acetylsalicylic acid, or ASA) reduces the number of HIV target cells in the genital tract by 35 per cent. They will now further investigate this connection.

Working with a cohort of female sex workers in Nairobi, Kenya who are highly exposed to HIV and are using anti-HIV drugs for prevention, the team will place women with high levels of genital inflammation on the anti-inflammatory drug ASA to assess if the number of HIV target cells in the genital tract is reduced. Meanwhile, in the laboratory, they will use mice with a human immune system to determine the mechanism of how ASA affects the migration of HIV target cells and they will perform HIV infection studies to directly test is ASA can reduce HIV infection.

Finally, because taking drugs daily can be challenging for some people, the team will assess in the humanized mouse model, the long-term goal of using an intravaginal ring that would deliver a contraceptive, an anti-HIV drug, and an anti-inflammatory drug. This proposal will determine if their “Combination HIV Prevention” approach is more effective, thereby providing women with more options for protecting themselves.

 

Burgener’s project: The microbiome in HIV prevention

Co-Principle investigators: Carolina Herrera (Imperial College, London); Roger Paredes (Irsi Caixa, Barcelona)

Co-Investigators: Vanessa Poliquin (Obstetrics, Gynecology and Reproductive Sciences, U of M) and Thomas Murooka (Department of Immunology-UM)

The microbiome has been associated with increased risk of HIV acquisition, but this has not been studied extensively in the context of HIV prevention technologies, such as anti-retroviral based pre-exposure prophylaxis and vaccines. In this study, Burgener and his team will evaluate how differences in the microbiome of genital tract and gut affect host inflammation, the effectiveness of these drugs, and immune responses stimulated by HIV vaccines. These studies may help us to improve these products to make them more effective for HIV prevention.

This project, in collaboration with IrsiCaixa AIDS Research Institute, builds on Burgener’s past work that discovered the effectiveness of an anti-HIV gel known as tenofovir is related to the presence of “healthy” lactobacillus bacteria in vaginal tract, meaning those women who lacked this bacteria gained little or no benefit from the drug.  

“This was a striking result, and made us think that there was some interaction between some bacteria and tenofovir,” Burgener, who is also a Research Scientist with the Public Health Agency of Canada, said at the time.

Burgener’s team was the first to show that vaginal bacteria can impact this class of anti-retroviral drugs, and their efficacy can vary more than three-fold depending on what bacteria are dominant in the person.

Research at the University of Manitoba is partially supported by funding from the Government of Canada Research Support Fund.

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