Mr Philip Arandjelovic - Infection division

Mr Philip Arandjelovic - Infection division

Location: 
Davis Auditorium
Start Time: 
Mon, 04/03/2019 - 3:00pm
End Time: 
Mon, 04/03/2019 - 4:00pm

Investigating clinical therapeutics to kill infected cells and promote HIV clearance

​PhD Completion seminar

HIV/AIDS continues to be a significant cause of global morbidity and mortality. While antiretroviral therapy (ART) is effective in suppressing HIV replication, the integration of provirus into long-lived memory CD4+ T cells is a major barrier to cure. Attempts to reactivate and purge this latent reservoir have failed, highlighting the need for alternative strategies geared towards killing latently infected cells. The longevity of the reservoir population points to intrinsic survival mechanisms which may be exploited by cell death-inducing compounds. Clinical-stage BH3-mimetics, such as venetoclax, represent a novel approach to antagonising the survival of latently infected host cells.
 
Phil employed a humanised mouse model of HIV infection which recapitulates key stages of human disease, including chronicity and long-lived viral reservoirs that can be controlled with ART. HIV infected, virally suppressed humanised mice were administered BH3-mimetics for defined periods, followed by targeted ART interruption to assess impacts on the latent reservoir as measured by viral rebound. This research reveals a novel approach to kill latently infected cells in vivo, which is an essential component of achieving an HIV cure.