Nicolas Chomont and Andrés Finzi, two researchers at the CHUM Research Centre (CRCHUM), have received $5.75M in research funding from the Canadian Institutes of Health Research as part of the HIV/AIDS and STBBI Research Initiative.

Their two projects are part of a small cohort of six funded studies in Canada.

The project, led by Nicolas Chomont, is receiving $3.75M over five years and is the continuation of the CanCURE initiative, a research consortium dedicated to the development of an HIV cure protocol and launched ten years ago by Éric Cohen of the Montreal Clinical Research Institute.

“In this project, we will try to understand in which tissues viral reservoirs are preferentially located, by what mechanisms the virus manages to hide there, and also how to find it," explains the researcher, who will be able to count on the expertise of 14 other Canadian researchers involved in CanCURE.

Petronela Ancuta, a CRCHUM researcher, is part of this team. About twenty other specialists from around the world will also be called upon. CanCURE will benefit from the recommendations of a six-member community advisory board representing various communities of people living with HIV in Canada.

Andrés Finzi's team, receiving a $2M grant over five years, is considering a new way to detect and dispose of reservoirs using CD4-mimetic compounds, which are known to increase the immune response against HIV.

He will draw upon the expertise of collaborators in the United States, his colleague at the CRCHUM Martine Tétreault and his business partner, Immune Biosolutions.

What really happens in tissues?

Although antiretroviral therapy (ART) has significantly increased the life expectancy of people living with HIV, the virus has the ability to persist in the body, especially in tissues (intestine, lymph nodes, lungs, brain, etc.).

With exclusive access to tissues from living and deceased donors, the Canadian team led by Nicolas Chomont will focus on better understanding how HIV-infected cells preferentially persist in intestinal mucous membranes and lymphoid tissues.

The team will identify the mechanisms involved in viral rebound when ART is discontinued and how these can be targeted for therapeutic purposes.

Clinical trials are planned over the next five years and will aim, among other things, to reduce the activity of HIV reservoirs during ART through fecal microbiota transplantation.

A matter of envelopes

Most people living with HIV and on ART have the immune arsenal to eliminate cells infected with the virus, but fail to do so.

Why? Andrés Finzi and his Canada-U.S. team believe that this is most likely because their immune system cannot detect the virus’s envelope glycoprotein (Env).

“We have developed “Env-Flow,” a new method to detect the cells that make up the reservoir. This allows us to identify and better characterize them,” says Andrés Finzi. “In this project, we’re also going to test ways of waking up the virus in these infected cells so that it produces Env and thus facilitates its recognition by the immune system.”

The use of CD4-mimetic compounds will enhance the eradication capacity of specialized immune cells.

This research will be carried out in the laboratory on cells from people living with HIV and on an animal model.

Nicolas Chomont and Andrés Finzi's research teams ultimately aim to develop a safe and effective treatment to eradicate HIV.