Elite HIV Controllers: Myth or Reality?

Despite the varying disease progression rates, the majority of HIV-infected individuals eventuallyprogress to AIDS. There is a subset of HIV-positive individuals, who maintain high CD4+ and CD8+T-cell counts, remain therapy naive and persistently infected with HIV-1 for more than 15 to 20 years.In light of current observations, this subset can be divided into two groups. One shows low detectableplasma viremia (< 5000 HIV-RNA copies/ml), termed long-term nonprogressors. A second groupshows plasma HIV-RNA values persistently below 50 copies/ml throughout the course of infection,and termed “eliteâ€? or “natural controllersâ€?. The features common between both groups are the presenceof high CD4+ and CD8+ T-cell counts, strong immune responses, and low but variable cellularproviral DNA load. The group of HIV-positive long-term nonprogressor individuals comprises about1% of the total HIV population in the world, whereas the “eliteâ€? controllers may be much less. Whydo some people deteriorate faster, while others remain normal both symptomatically and immunologicallyfor decades? There is a renewed interest in HIV-positive individuals who have survived sincethe period close to the earlier part of the HIV pandemic in the 1980s and have remained drug-naive.As very little is known about “eliteâ€? controllers, the findings discussed here are largely based onpreviously known and newly emerging aspects of HIV pathogenesis in the context of the long-termnonprogressor group. It is believed that data emerging on long-term nonprogressors will allow us tomake scientific inferences to further our research on “eliteâ€? controllers. Aspects dealing with cellular,humoral, innate, and adaptive immunity, which are relevant to nonprogressive HIV disease, are beyondthe scope of this review.