Targeting HIV persistent reservoirs: Evaluation of new classes of latency reversing agent as part of novel strategies for HIV cure approaches

With 37 millions people currently living with HIV and 2.6 million people newly infected worldwide, the AIDS pandemic is a global health crisis. In Ireland, the HSE and the HSPC have made HIV/AIDS "a notifiable disease and a major public health importance". 30 years of intense HIV/AIDS research have provided efficient antiretroviral treatments resulting in viral suppression and saving lives, but there is still no cure for AIDS. Indeed, HIV hides and "goes to sleep" in latent reservoirs, where it remains invisible from available drugs and host immune defenses, and resurfaces as soon as therapy is discontinued. Current and worldwide HIV-1 cure research efforts focus on developing new strategies to reactivate or "awaken" HIV latent reservoirs in order to purge the virus from infected individuals. The main advantages of these "Shock and Kill" strategies would be to alleviate the need for life long treatment -associated with substantial costs and long-term side effects- and importantly to curb the HIV/AIDS epidemic. While encouraging, these strategies have only been able to reactivate a fraction of the latent reservoir, which underscores the intricate and multi-layered nature of the blocks keeping the virus dormant.

In this context, and based on our new understandings of what lies beneath the surface of the latent HIV reservoir, we have devised a novel latency-reversing strategy which aim to inhibit and unlock a new type of cellular block, discovered by our laboratory that maintain the virus dormant. Our pre-clinical programme will involve the systematic screening of novel classes of drugs specifically targeting this newly identified block using blood samples- where reside these latent reservoirs- from HIV infected individuals on antiretroviral treatments. Our pre-clinical study could be the first step towards the development a significant component of a cure for HIV.

Award Date
30 June 2017
Award Value
€368,922
Principal Investigator
Dr Virgine Gautier
Host Institution
University College Dublin
Scheme
Investigator Led Projects