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 beta2-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.

Estimates of HIV-1 incidence based on serological methods: a brief methodological review

“…All discrepant cases had undetectable viral load, that were identified as recent by the Vironostika S/LS assay but not with the Avidity assay, indicating that viral suppression affects the performance of cross sectional incidence assays based on antibody titer. Similar results were obtained for four long-term non-progressors/elite controllers from Brazil, who gave results compatible with recent infection based on the competitive BED-CEIA assay, whereas only 2 out of 4 were misclassified when using the avidity assay 66 .…”

CD4+T cells from elite suppressors are more susceptible to HIV-1 but produce fewer virions than cells from chronic progressors

“…Data from several groups, however, have suggested that cells lacking activation markers are also capable of being infected, and among activated cells there are differences in susceptibility to infection (39)(40)(41)(42)(43). We and others have previously shown considerably higher levels of CD4 + T-cell activation in CP than ES (36,44,45), and activation does not correlate with susceptibility to infection ex vivo in our system (36). To investigate the subset of CD4 + T cells most susceptible to infection, we infected unstimulated CD4 + T cells from uninfected donors using either X4-or R5-tropic virus.…”

Human immunodeficiency virus type 1 long-term non-progressors: the viral, genetic and immunological basis for disease non-progression

“…1.5 years) they have elevated levels of immune activation and spontaneous T-cell apoptosis similar to treated HIV-infected subjects or untreated rapid progressors (Ronquillo et al, 2010;Goicoechea et al, 2009). Low levels of virus replication probably explain for the presence of T-cell activation in controllers and progressors earlier in infection and which has been shown to decline over time in controllers, but not in progressors (Bello et al, 2009). …”

“…+ Tcell activation in comparison with subjects with rapid disease progression (Bello et al, 2009;Marchetti et al, 2009). Less CD4 + T-cell immune activation reduces the number of cells susceptible to HIV-1 infection and can potentially lead to a better disease prognosis.…”

“…Less CD4 + T-cell immune activation reduces the number of cells susceptible to HIV-1 infection and can potentially lead to a better disease prognosis. In one study, ECs (n54) that were examined longitudinally for 4 years had low levels of immune activation (measured as HLA-DR + CD38 + cells) and spontaneous CD4 + T-cell apoptosis similar to uninfected controls and less than progressors (Bello et al, 2009). …”