Elite control of HIV: is this the right model for a functional cure?

• Controllers maintain low levels of plasma HIV, however virus is easily detectable and likely replication-competent.
• The precise mechanisms of viral control are unknown and may be relevant for cure research.
• The mechanisms that limit viral replication may result in increased inflammation and activation.
• Elite controllers may benefit from antiretroviral therapy.

A cure for HIV is still greatly needed and has become a global research priority. A unique subset of HIV-infected individuals who spontaneously control HIV exists, and these are known as ‘elite controllers’. They may represent a natural model for a ‘functional cure’ in which there is long term control of viral replication and remission from symptoms of HIV infection in the absence of antiretroviral therapy. However, controllers have evidence of ongoing inflammation, CD4+ T cell depletion, and perhaps even inflammation-associated cardiovascular disease, suggesting that this natural long term virologic control may be coming at an immunologic and clinical cost. These individuals may continue to provide continued insights into mechanisms of host control; however, they may not represent the best model of a functional cure, if we believe that a cure should require a disease-free (and not just a treatment-free) state.