Scientific Research Project Title

Eliminating the HIV reservoir that persists on antiretroviral therapy by targeting the cell death regulator, BCL-2

Research Institution

Aarhus University

Aarhus University

Research field

Infection Medicine

Research leader

Thomas Aagaard Rasmussen

Associate Professor and Associate Clinical Director, HIV Cure Studies

Project title

Eliminating the HIV reservoir that persists on antiretroviral therapy by targeting the cell death regulator, BCL-2

What is your project about?

The main barrier to curing HIV is the persistence of virus in long-lived cells despite effective antiviral treatment. It has recently been shown that this long-term persistence of infected cells is underpinned by changes in cell death pathways, which can be targeted by inhibiting BCL-2, a key factor involved in regulating cell death and survival. By conducting the first clinical trial in HIV of a drug that alters cell death pathways, we aim to establish the safety of the BCL-2 inhibitor, venetoclax, in people with HIV and determine whether venetoclax can eliminate HIV-infected cells. By applying technological advances to measure HIV persistence as well as changes in cell death pathways and immune function, the study will provide an integrated understanding of the involved mechanisms. Collectively, this will clarify whether impacting cell death pathways might contribute to a cure for HIV and will provide critically important data for future studies with venetoclax alone or in combination with other interventions for HIV cure.

How did you become interested in your particular field of research?

My interest for HIV and, in particular, research towards a cure for HIV began more than 10 years ago, when I was preparing my PhD and researching various scientific topics. The ability of HIV to persists long-term despite anti-HIV immune responses and highly potent antiviral therapy is a formidable challenge and a problem with global consequences. Addressing this problem requires a multi-disciplinary scientific approach to achieve an improved understanding of the basic virology, the host immune-pathogen interaction and not least which opportunities might exists for therapeutic intervention.

What are the scientific challenges and perspectives in your project?

The primary barrier preventing a cure for HIV is persistence of latent virus in long-lived cells of the immune system. Recent studies indicate that long-term persistence is underpinned by changes in cell death pathways. In this study we will test whether therapeutically targeting the involved cell death pathways can induce killing of latently infected cells. If successful this will open for new therapeutic approaches that may contribute to developing a cure for HIV.

What is your estimate of the impact, which your project may have to society in the long term?

The development and clinical implementation of drugs that promote cell death has led to significant improvements in the management of certain cancers in recent years. This project will further our understanding of how these advances of inducing cell death can be harnessed for the cure of chronic infections.

Which impact do you expect the Sapere Aude programme will have on your career as a researcher?

I recently returned to Denmark after spending 3 years abroad in a lab focused on HIV persistence research. The Sapere Aude grant will be a central component in my efforts to develop a scientific program capable of impacting the international research agenda on HIV cure. The support from the Sapere Aude program will also provide good opportunities for maintaining and expanding productive international collaborations.

Background and personal life

I am 45 years old, married and the father of 3 wonderful children. I my spare time I particularly enjoy running, traveling, reading and talking - and not least spending time with friends and family.

City of your current residence

Aarhus

High school

Middelfart