WEHI PhD Completion Seminar hosted by Dr Marcel Doerflinger

Le Wang
PhD Student – Doerflinger Laboratory, Infection and Global Health division

Depleting the HIV Reservoir by Manipulating Cell Death Pathways

Davis Auditorium

Join via TEAMS

Including Q&A session

HIV/AIDS poses a significant global health threat. Despite effective suppression of HIV viremia by antiretroviral therapy (ART), HIV persists lifelong in people living with HIV. This persistence is mediated by the presence of a viral reservoir consisting of latently infected cells harbouring intact HIV proviruses, which can drive viral rebound after ART interruption. A functional cure for HIV remains needed.

During my PhD, I used a humanised immune system (HIS) mouse model to investigate the impact of cell death–inducing agents on persistent HIV-1 infection. I found that xevinapant, a monovalent SMAC mimetic that targets the extrinsic apoptosis pathway via IAP antagonism, reduced levels of intact HIV-1 proviral DNA in lymphoid tissues of HIS mice. Moreover, xevinapant treatment led to a significant delay in viral rebound following ART interruption. The combination of xevinapant with the BH3 mimetic venetoclax was also thoroughly evaluated.

These findings reveal a survival vulnerability of the HIV reservoir and shed light on a potential new approach for HIV cure strategies.

All welcome!