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 challenging for many. 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, and/or neurocognitive decline.
These health problems, categorized as 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 Madeleine Durand, MD, FRCPC, MSc, assistant professor at Université de Montréal and researcher at CHUM Research Centre (CRCHUM).
Durand worked with Cécile Tremblay, MD, on 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.
Counteracting toxic effects
In a study submitted to The Journal of Infectious Diseases, scientists demonstrate a link between inflammation in people living with HIV and the level of an HIV protein, gp120, in the blood. This molecule makes up a part of the entry “key” 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 with chronic inflammation leading to comorbidities,” explains Andrés Finzi, PhD, researcher, 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 Durand. These individuals are over 40 years, have been living with HIV for 16 years on average, have received 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 Finzi.
Clinical trial in 2024
Encouraged by the results of this study, Durand and Finzi are setting up a randomized, double-blind clinical trial to determine if targeting the gp120 would decrease inflammation and reduce the risk of early-onset comorbidities.
“In our multicenter 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 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 percent of the recruits to be women.
Women living with HIV represent 23 percent of the 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 Durand.
- This press release is supported by the University of Montréal Hospital Research Centre (CRCHUM)