[Elite controllers and the mechanisms behind spontaneous control of HIV]

Elite controlllers (EC) are a unique and rare group of HIV-positive patients who control viral replication to undetectable levels in the absence of antiretroviral treatment. They tend to maintain stable CD4 count, and do not progress to AIDS. While the mechanisms underlying elite control are currently under intensive investigation, research has revealed that a set of host genetic and acquired factors, as well as specific viral characteristics, contribute to viral containment. One of the central genetic markers consistently associated with control is specific class I HLA molecules, especially HLA-B5701, highlighting the role of potent cytotoxic T cell responses in eliminating HIV-infected cells and restricting the viral reservoir. A significant contribution was also attributed to T helper cells, regulatory T cells and several cell subsets of the innate immune system including natural killer (NK) cells. Studies characterizing viruses from EC found inconsistent results showing both highly mutated viruses with reduced fitness, and virulent, fully replication-competent viruses, leaving open the question of host-mediated control versus intrinsic viral attenuation as the cause for extremely low viral reservoirs in elite controllers. Further understanding of the mechanisms behind spontaneous control of HIV infection is imperative, and might prove important for efforts to develop a prophylactic and therapeutic HIV vaccine.