HIV: Thwarting a protein in the hope of a better quality of lifeUNIVERSITY OF MONTREAL HOSPITAL RESEARCH CENTRE (CRCHUM)
Andrés Finzi (left), a CRCHUM researcher, with Mehdi Benlarbi, a doctoral student in Finzi's lab and the study’s first author, and Dr. Madeleine Durand (right), a CRCHUM researcher. CREDIT CHUM
Montreal, December 1, 2023—To mark the occasion of World AIDS Day, find out how Dr. Madeleine Durand and Andrés Finzi are working to reduce chronic inflammation and the risk of comorbidities in people living with HIV.
In Canada, more than 43,000 people are living with a virus well controlled by antiretroviral therapy. However, aging in good health and enjoying a good quality of life is still a challenge for many of them.
The sustained activation of the body’s immune system for people living with HIV leads to chronic inflammation that for some people can cause associated complications such as cardiovascular diseases, osteoporosis or neurocognitive decline.
These health problems, categorized under the term early-onset comorbidities, are linked to the viral reservoirs in which HIV persists.
“These comorbidities arise approximately 15 years earlier in people living with HIV, and this gap has not gotten any narrower over the last decade. Today, there is no specific treatment for HIV to slow down this premature aging,” says Dr. Madeleine Durand, assistant professor at Université de Montréal and researcher at CHUM Research Centre (CRCHUM).
A world-renowned specialist, she worked with Dr. Cécile Tremblay the first Canadian HIV and Aging Cohort Study (CHACS), which included 850 people living with HIV and 250 control subjects.
This important source of data and specimens is helping several research teams across Canada to understand how these individuals age differently.
One of her colleagues, Andrés Finzi, researcher at CRCHUM, called on her.
“Andrés is the man who plays with bits of protein,” jokes Madeleine Durand. “She’s not wrong,” he replies, amused.
Their collaboration is largely due to coincidence: a chance encounter at a scientific conference at CHUM in 2021. During the lunch that followed, they devised some research hypotheses. One of them was fruitful.
Counteracting toxic effects
In a study published by The Journal of Infectious Diseases, whose primary author, Mehdi Benlarbi, is doing his doctorate in Andrés Finzi’s lab, scientists demonstrate that there is a link between inflammation in people living with HIV and the level of protein gp120 in the blood. This molecule makes up a part of the entry “key” that the virus uses to infect human cells.
“Even when the viral load is undetectable, we were able to detect this molecule in the blood of one in three infected people. We’re showing that it acts as a toxin and is associated to chronic inflammation leading to comorbidities,” explains Andrés Finzi, professor at Université de Montréal and chair holder of the Canada Research Chair in Retroviral Entry.
To achieve these results, the researcher’s team measured the level of gp120 in the plasma of 386 people from the CHACS cohort led by Dr. Durand. These individuals are over 40-year-old, have been living with HIV in average for 16 years, receive antiretroviral therapy and have an undetectable viral load.
“We’ve managed to counteract the harmful effects of gp120 in vitro by using Fostemsavir, a drug only used by people who are resistant to traditional anti-HIV treatments and whose viral load is detectable,” says Andrés Finzi.
Clinical trial in 2024
Encouraged by the results of this study, Dr. Madeleine Durand and Andrés Finzi are setting up a randomized, double-blind clinical trial to determine if targeting the gp120 would decrease inflammation, thereby reducing the risk of early-onset comorbidities.
At this stage, Durand and Finzi have been able to rely on financial support from the Canadian Institutes of Health Research, from the CIHR Canadian HIV Trials Network and from the Fonds de recherche du Québec—Santé to allow them to set up their clinical trial.
“In our multicentre trial that will last two years, we’re going to concretely examine if adding Fostemsavir to existing antiretroviral therapy treatments leads to a reduction in cardiovascular diseases. This will be determined by the change in the volume of atherosclerosis in coronary arteries between the end and the start of the study, measured by cardiac CT scans,” explains Dr. Durand.
Patients’ frailty over time and cognitive abilities will also be evaluated.
The clinical trial is set to start in September 2024. Approximately 200 individuals will be recruited based on the same criteria as those in the CHACS cohort. The goal is for 50% of the recruits to be women.
Women living with HIV represent 23% of people affected in Canada and form the second fastest-growing group, after Indigenous people. However, women are systematically underrepresented in HIV trials.
“If our trial proves to be conclusive, there would be a paradigm shift in current treatment. Our personalized approach to medicine, which includes optimizing antiretroviral therapy in the many people for whom gp120 is detectable, could relieve the burden of their comorbidities and improve their quality of life,” reports Dr. Durand.
According to the World Health Organization, more than 39 million people were living with HIV at the end of 2022.
Science writing : Bruno Geoffroy
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About the study
The article "Plasmatic HIV-1 soluble gp120 is associated with correlates of immune dysfunction and inflammation in ART-treated individuals with undetectable viremia" by Mehdi Benlarbi and his colleagues was published on November 30, 2023 in The Journal of Infectious Diseases. The study received funding mainly from the Fonds de Recherche du Québec-Santé, the Canadian Institutes of Health Research, the Canada Foundation for Innovation and the U.S. National Institutes of Health.
About the CHUM Research Centre (CRCHUM)
The Hospital Research Centre of the Université de Montréal (CRCHUM) is one of the leading hospital research centres in North America. Its mission is to improve adult health through a research continuum that includes disciplines such as basic science, clinical research and population health. More than 2,150 people work at the CRCHUM, including nearly 500 researchers and some 650 students and postdoctoral fellows. crchum.com
About the Université de Montréal
Anchored in Montreal but with an international vocation, the Université de Montréal is one of the world’s largest universities, especially when it comes to Francophone universities. Founded in 1879, it boasts 13 faculties and schools today. With its two affiliates schools, HEC Montréal and Polytechnique Montréal, it is Quebec’s leading higher education and research hub and one of the largest in North America. 2,300 professors and researchers work at the Université de Montréal and over 70,000 are enrolled. umontreal.ca
JOURNAL
The Journal of Infectious Diseases
METHOD OF RESEARCH
Experimental study
SUBJECT OF RESEARCH
Human tissue samples
ARTICLE TITLE
Plasmatic HIV-1 soluble gp120 is associated with correlates of immune dysfunction and inflammation in ART-treated individuals with undetectable viremia
ARTICLE PUBLICATION DATE
30-Nov-2023
Media Contacts
Bruno Geoffroy
University of Montreal Hospital Research Centre (CRCHUM)
bruno.geoffroy.chum@ssss.gouv.qc.ca
@CRCHUM
Andrée-Anne Toussaint
University of Montreal Hospital Research Centre (CRCHUM)
andree-anne.toussaint.chum@ssss.gouv.qc.ca
Office: 514-890-8000 x23675
@CRCHUM
Source: https://www.eurekalert.org/news-releases/1009376
"Reproduced with permission - "UNIVERSITY OF MONTREAL HOSPITAL RESEARCH CENTRE (CRCHUM)"
UNIVERSITY OF MONTREAL HOSPITAL RESEARCH CENTRE (CRCHUM)
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