Elite controllers as a model of functional cure

The limitations of life-long antiretroviral therapies for the HIV infection lead to a novel concept of a functional cure developing innovative therapeutic strategies to generate a long-term remission of HIV replication without treatment. This concept requires an understanding of the mechanisms by which HIV is controlled in conditions of undetectable virus replication, before developing ambitious therapies blocking durably viral replication - and ultimately eradicating HIV.Recent literature shows that the exceptional elite controller status is usually not driven by virus gross genetic defects, despite some virus attenuation resulting from immune selective pressure, but is frequently determined by host's genetic factors permitting robust cell-mediated immunity to control the virus replication and reservoirs. Lack of immunity and immune deficiency can however limit this model in some cases and only a subgroup in whom both the virus and the immune deficiency are controlled, that is the elite long-term controllers, might represent the best current model for a functional cure.This review examines whether the exceptional HIV-infected elite controllers, who spontaneously and durably maintain extremely low virus replication, might be considered as a model for a functional cure and whether the mechanisms identified in these exceptional individuals might serve to identify therapeutic or vaccine strategies.