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HIV Cure-Related Research Workshop Report

January 7, 2012 - December 6 to 9, 2011 were days of intense discussions between more than 210 international scientists meeting for the 5th edition of the "International Workshop on HIV Persistence, Reservoirs and Eradication Strategies". Launched in 2003, this biennial research workshop focuses on the mechanisms of HIV persistence in antiretroviral therapy (ART) treated patients, and way to eradicate it. Over the years, it has been recognized as the reference research workshop in the field and is organized under the auspices of the National Institutes of Health (NIH) and the French Agency for AIDS Research (ANRS).

As insights into the mechanisms allowing and maintaining HIV latency continue to develop, 3 major ways for an HIV cure are emerging:
The first one is more potent ART regimens.

According to data presented at the workshop, current ART combinations fail to reach lymphoid tissues at effective levels. Developing new ways of delivering ART to the tissues and the central nervous system is top priority. The second one is induction of HIV expression without cell activation.
Several potent anti-latency agents, like vorinostat and bryostatin, have been identified to reactivate HIV from latency. Delivering these drugs incorporated in cellular organelles, like vaults, could reduce their toxicity and better target the infected cells. It is mandatory to test combinations of these agents to purge a wide range of latently infected cells and viral variants subtypes.
The third one is immune modulation. Interleukin-15 is a cytokine able to reactivate HIV from resting cells without leading to an expansion of the HIV reservoir like with interleukin-7.
The PD-1 pathway is an important signaling system involved in HIV persistence. Anti-PD-1 antibodies could restore the specific anti-HIV immune responses and help eradicate the few infected cells that will remain after administrating anti-latency agents.

Researchers think that a unique approach will not be enough to purge and control all the different subsets of latently infected cells. It is therefore needed to implement pilot studies testing a combination of these new strategies or their sequential administration. Life long ART will be unsustainable for the 34 million infected patients worldwide, with a majority in poor-resource countries. It is therefore urgent to engage the best researchers from academia and industry in a concerted effort towards an HIV cure.

Creating and funding an international agency to specifically coordinate this cure research would be a political initiative that the next generations will remember.

These researchers will reconvene in Miami, Florida, December 2013 for the 6th edition of the "International Workshop on HIV Persistence, Reservoirs and Eradication Strategies". Meanwhile, they remain connected via professional websites and seminars to advance the design of the HIV eradication clinical trials. However, a clear political will and an interest from investors in finding an HIV cure still need to be obtained.


Alain Lafeuillade
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