Unlocking HIV-1 latency with metabolic cues

With 35 million people currently leaving with HIV and 1.6 million people worldwide who died from HIV in 2012, the AIDS pandemic is a major 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, but there is still no cure for AIDS. Indeed, HIV hides and goes to sleep in latent reservoirs, where it remains invisible from drugs and 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 understandings of what lies beneath the surface of the latent HIV reservoir, we have devised a novel latency-reversing strategy targeting multiple metabolic junctions that could keep the virus dormant. Our pre-clinical programme will first involve the systematic screening of drugs targeting key metabolic actors using in vitro models of HIV latency. Subsequently, the activity of the most performant latency-reversing drug combinations will be tested 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
20 June 2014
Award Value
€329,332
Principal Investigator
Dr Virginie Gautier
Host Institution
University College Dublin
Scheme
Health Research Awards