Robust HIV-specific CD4+ and CD8+ T-cell responses distinguish elite control in adolescents living with HIV from viremic nonprogressors. (1st January 2022)

• Record Type: Journal Article
• Authors: Vieira, Vinicius A.; Millar, Jane; Adland, Emily; Muenchhoff, Maximilian; Roider, Julia; Guash, Claudia Fortuny; Peluso, Denise; Thomé, Beatriz; Garcia-Guerrero, Maria C.; Puertas, Mari C.; Bamford, Alasdair; Brander, Christian; Carrington, Mary; Martinez-Picado, Javier; Frater, John; Tudor-Williams, Gareth; Goulder, Philip
• Is Part Of: AIDS. Volume 36:Number 1(2022)
• Publication Date: 2022-01-01
• Subjects: elite controllers -- immune activation -- pediatrics -- T-cell response -- viral control; AIDS (Disease) -- Periodicals; Acquired Immunodeficiency Syndrome; AIDS (Disease); Periodicals; Periodicals; 616.9792005
• DOI: 10.1097/QAD.0000000000003078
• Languages: English
• ISSNs: 0269-9370

Abstract

Abstract : Background: Elite controllers are therapy-naive individuals living with HIV capable of spontaneous control of plasma viraemia for at least a year. Although viremic nonprogressors are more common in vertical HIV-infection than in adults' infection, elite control has been rarely characterized in the pediatric population. Design: We analyzed the T-cell immunophenotype and the HIV-specific response by flow cytometry in four pediatric elite controllers (PECs) compared with age-matched nonprogressors (PNPs), progressors and HIV-exposed uninfected (HEUs) adolescents. Results: PECs T-cell populations had lower immune activation and exhaustion levels when compared with progressors, reflected by a more sustained and preserved effector function. The HIV-specific T-cell responses among PECs were characterized by high-frequency Gag-specific CD4 + T-cell activity, and markedly more polyfunctional Gag-specific CD8 + activity, compared with PNPs and progressors. These findings were consistently observed even in the absence of protective HLA-I molecules such as HLA-B*27/57/81. Conclusion: Pediatric 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 viremia, 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 posttreatment controllers, in whom protective HLA-I molecules are not the main factor. Abstract : Supplemental Digital Content is available in the text