Immune activation and antibody responses in non‐progressing elite controller individuals infected with HIV‐1

Abstract 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 (<50–80 copies/ml of plasma) for >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 β2‐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 over time. 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. © 2009 Wiley‐Liss, Inc.