Immune Activation and Antibody Responses in Non-Progressing Elite Controller Individuals Infected With HIV-1

An extremely rare subset of patients infected with HIV-1 designated as "non-progressing elite controllers" appears to be able to maintain stable CD4 + T-cell counts and a median plasma viremia below the detection limit of current ultrasensitive assays (10 years in the absence of antiretroviral therapy. Lymphocyte subsets (CD4 +, CD8 +), immune activation markers (HLA-DR +, CD38 +, Beta-2-microglobulin), and HIV-specific antibody responses were longitudinally examined in four non-progressing elite controllers over more than 5 years. Two control groups of seronegative healthy individuals and untreated patients infected with HIV-1 presenting detectable viremia were also included. None of the non-progressing elite controllers displayed the high T-cell activation levels generally seen in the seropositive individuals, keeping them within the normal range. Three non-progressing elite controllers showed no significant immune system abnormalities when compared to seronegative individuals, displaying a low proportion of HIV-1-specific binding antibodies and low avidity index, similar to those observed for individuals infected recently with HIV-1. One non-progressing elite controller exhibited CD8 + T-cell counts and beta 2-M levels above normal ranges and developed a low but "mature" (high-avidity) HIV-1-specific antibody response. Thus, the non-progressing elite controllers are able to maintain normal T-cell activation levels, which may contribute to prevent, or greatly reduce,the damage of the immune system typically induced by the HIV-1 overtime. They are, however, immunologically heterogeneous and very low levels of antigen exposure seem to occur in these patients, sufficient for sustaining a low, but detectable, HIV-1-specific immunity. J. Med Virol. 81:1681-1690,2009. (C) 2009 Wiley-Liss, Inc.