HIV reservoirs continually stimulate the immune system

- EN - DE- FR- IT
Daniel Kaufmann. In the microscopy photograph in the background, the green and m
Daniel Kaufmann. In the microscopy photograph in the background, the green and magenta dots indicate different parts of HIV expressed in a CD4 T lymphocyte. Credits: Microscopy image by Aurélie Cleret-Buhot and Mathieu Dubé (CRCHUM); Photography: ©CHUV / Gilles Weber
Scientists at CHUV and the University of Lausanne have shown that in people living with HIV and taking antiretroviral treatment, cells functioning as "reservoirs" continue to produce parts of the virus that continually stimulate the immune system. This discovery opens the way to new therapeutic approaches.

Today, people living with HIV benefit from effective antiretroviral treatment (ART). In over 95% of those on treatment, the virus is undetectable in the blood and non-transmissible. However, it persists in rare cells that function as "reservoirs". The existence of these hidden refuges of HIV, long considered dormant or ’latent’, poses a fundamental challenge to achieving a cure.

In a study published in the prestigious journal Cell Host & Microbe, the team led by Prof. Daniel Kaufmann, world expert in HIV, Head of the Infectious Diseases Department at CHUV, Professor at the Faculty of Biology and Medicine at the University of Lausanne and Visiting Professor at the University of Montreal, shows that in the majority of participants, HIV reservoirs can continue to be active even after years of antiviral treatment. They then manufacture parts of the virus, over-stimulating the immune system.

New technique for detecting virus reservoirs

The virus lives and replicates mainly in one type of white blood cell: CD4 T lymphocytes. CD4 T cell populations are highly variable. To develop new targeted treatments aimed at either eliminating or completely blocking these residual infected cells, we need to find out exactly what type of CD4 T lymphocytes the virus harbors in, and what their properties are. Prof. Kaufmann’s work, carried out between Montreal and Lausanne, has led to the development of an innovative and particularly sensitive laboratory technique for detecting these reservoirs. It enables a "photo" to be taken of each individual cell harboring the virus, and then isolated for analysis of the virus it harbors.

In the majority of participants, the researchers identified CD4 reservoir cells which, despite currently available antiretroviral treatments, expressed parts of the hidden virus. The scientists made another intriguing observation: the vast majority of the active viruses thus identified carried mutations that rendered them incapable of producing complete new viral particles. Despite their anomalies, these viruses nevertheless appear to have a significant impact on the immune system. Indeed, these active reservoirs continuously stimulate the immune system, which could lead to its exhaustion", observes Prof. Kaufmann.

Chronic inflammation

This research confirms a link between HIV reservoir activity and constant stimulation of the immune system in people undergoing antiviral treatment. It also raises the hypothesis of a link between these virus reservoirs and the chronic inflammation observed in a proportion of people living with HIV. The persistence of chronic inflammation in people living with HIV despite antiretroviral treatment can lead to long-term health problems, including a doubled risk of cardiovascular disease and manifestations of premature aging (osteoporosis, neurological disorders, etc.).

In collaboration with scientists from Switzerland, Canada and the USA, Daniel Kaufmann’s research team plans over the coming months to evaluate this hypothesis of a link between active HIV reservoirs and inflammation, as well as the quality and mechanisms of defense against the virus.

about the study

Prof. Daniel Kaufmann, the study’s first investigator, has worked at the Centre hospitalier universitaire de Montréal (CHUM) as a physician and researcher for some ten years. In 2022, he was appointed Head of the Infectious Diseases Department at CHUV. A world specialist in HIV, his work, which began in Montreal, is now continuing in Lausanne.

The article Spontaneous HIV expression during suppressive ART is associated with the magnitude and function of HIV-specific CD4+ and CD8+ T cells, by Mathieu Dubé and colleagues, was published on September 13, 2023 in the journal Cell Host & Microbe, and is the subject of a journal editorial comment.

Funding for the study was provided by the Canadian Institutes of Health Research (CIHR), the U.S. National Institutes of Health (NIH), the Fonds de Recherche du Québec-Santé (FRQS) and the Réseau SIDA et maladies infectieuses du Fonds de Recherche du Québec-Santé.