Robust HIV-specific CD4+ and CD8+ T-cell responses distinguish elite control in adolescents living with HIV from viremic nonprogressors.

Vieira VA., Millar J., Adland E., Muenchhoff M., Roider J., Guash CF., Peluso D., Thomé B., Garcia-Guerrero MC., Puertas MC., Bamford A., Brander C., Carrington M., Martinez-Picado J., Frater J., Tudor-Williams G., Goulder P.

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.

DOI

10.1097/QAD.0000000000003078

Type

Journal article

Publication Date

2022-01-01T00:00:00+00:00

Volume

36

Pages

95 - 105

Total pages

10

Keywords

Adolescent, Adult, CD4-Positive T-Lymphocytes, CD8-Positive T-Lymphocytes, Child, HIV Infections, HIV-1, Humans, Viral Load, Viremia

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