Robust HIV-specific CD4+ and CD8+ T-cell responses distinguish the rare phenotype of elite control in adolescents living with HIV from viraemic non-progressors.

Abstract

BACKGROUND\nElite controllers (ECs) are therapy-naïve HIV-infected individuals capable of spontaneous control of plasma viraemia for at least a year. Although viraemic non-progressors are more common in vertical HIV-infection than in adults infection, elite control has been rarely characterised in the paediatric population.\n\n\nDESIGN\nWe analysed the T-cell immunophenotype and the HIV-specific response by flow cytometry in four paediatric elite controllers (PECs) compared to age-matched non-progressors (PNPs), progressors (PPs) and HIV-exposed uninfected (HEUs) adolescents.\n\n\nRESULTS\nPECs T-cell populations had lower immune activation and exhaustion levels when compared to PP, reflected by a more sustained and preserved effector function. The HIV-specific T-cell responses among PECs were characterised by high-frequency Gag-specific CD4+ T-cell activity, and markedly more polyfunctional Gag-specific CD8+ activity, compared to PNPs and PPs. These findings were consistently observed even in the absence of protective HLA-I molecules such as HLA-B*27/57/81.\n\n\nCONCLUSIONS\nPaediatric elite control is normally achieved after years of infection, and low immune activation in PNPs precedes the increasing ability of CD8+ T-cell responses to achieve immune control of viraemia over the course of childhood, whereas in adults, high immune activation in acute infection predicts subsequent CD8+ T-cell-mediated immune control of viraemia, and in adult elite controllers low immune activation is therefore the consequence of the rapid CD8+ T-cell-mediated immune control generated after acute infection. This distinct strategy adopted by PECs may help identify pathways that facilitate remission in post-treatment controllers, where protective HLA-I molecules are not the main factor.