Elite HIV controllers: myth or reality?

Despite the varying disease progression rates, the majority of HIV-infected individuals eventually progress 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 detectable plasma viremia (< 5000 HIV-RNA copies/ml), termed long-term nonprogressors. A second group shows plasma HIV-RNA values persistently below 50 copies/ml throughout the course of infection, and termed "elite" or "natural controllers". The features common between both groups are the presence of high CD4+ and CD8+ T-cell counts, strong immune responses, and low but variable cellular proviral DNA load. The group of HIV-positive long-term nonprogressor individuals comprises about 1% of the total HIV population in the world, whereas the "elite" controllers may be much less. Why do some people deteriorate faster, while others remain normal both symptomatically and immunologically for decades? There is a renewed interest in HIV-positive individuals who have survived since the period close to the earlier part of the HIV pandemic in the 1980s and have remained drug-naive. As very little is known about "elite" controllers, the findings discussed here are largely based on previously known and newly emerging aspects of HIV pathogenesis in the context of the long-term nonprogressor group. It is believed that data emerging on long-term nonprogressors will allow us to make scientific inferences to further our research on "elite" controllers. Aspects dealing with cellular, humoral, innate, and adaptive immunity, which are relevant to nonprogressive HIV disease, are beyond the scope of this review.