Towards HIV Eradication and Cure

RESERVOIRS TASK FORCE

HIV Reservoirs Global Commitment

Struggling for an international society free of AIDS we understand that we have to tackle HIV persistence in HIV reservoirs with innovation, originality, rationale and creativity. Eradication of HIV-1 latency requires a prolonged scientific commitment to understanding the molecular mechanism of persistence, to safe and effective drug discovery, to rational design of therapeutic approaches, and to testing in adequate models before clinical application. Involvement of governmental agencies, research agencies, funding societies, pharmaceutical companies at their highest level is fundamental to build an effective task force against HIV reservoirs. We now need Pharmacologic strategies, which not only target viral replication but also deplete proviral infection and allow the clearance of persistently infected cells.

HIV Persistence in Reservoirs

The advent of antiretroviral therapy (ART) and the chronic suppression of HIV replication have been major medical successes, greatly increasing survival and improving quality of life. Successful ART results in clinically undetectable levels of plasma viremia (<50 copies/ml), allowing immune reconstitution. However, once infection is established, it cannot be cleared by current ART. Persistent proviral infection in a small pool of latently infected cells is insensitive to ART, is not detected by immune surveillance, and provides a long-lived source of rebound viremia: the "reservoir" of HIV infection.

New Therapeutic Strategies for HIV Reservoirs

HIV latency is a dynamic state and major progress has been made in the last 2 years to characterize and describe the factors involved in the restriction of HIV expression. This can already lead to translational research with several compounds capable to disrupt HIV latency. Histone deacetylase inhibitors, like SAHA, together with drugs able to activate P-TEFb like HMBA, or induce the Proteine Kinase C signaling pathway, like prostratin, are almost ready for evaluation. A combination or sequential administration of these drugs could be the best approach to purge the latent HIV reservoir. An immunologic complement will probably also be necessary in order to either inhibit survival of memory cells following homeostatic proliferation, or reinforce the immune control of a tiny persistent reservoir.

With the organization of the International Workshop on HIV Persistence and Reservoirs every 2-year since 2003, we are particularly committed in building this task force against HIV reservoirs.

 

HIV Cure

HIV Task Force