Impact of early antiretroviral therapy initiation on HIV-specific CD4 and CD8 T cell function in perinatally infected children

Stefano Rinaldi, Suresh Pallikkuth, Mark Cameron, Lesley R. De Armas, Nicola Cotugno, Vinh Dinh, Rajendra Pahwa, Brian Richardson, Shelly R. Saini, Salvatore Rocca, Maria G. Lain, Sion L. Williams, Paolo Palma, Savita Pahwa

Research output: Contribution to journalArticle

Abstract

Early initiation of antiretroviral therapy (ART) in vertically HIV-infected children limits the size of the virus reservoir, but whether the time of treatment initiation (TI) can durably impact host immune responses associated with HIV infection is still unknown. This study was conducted in PBMC of 20 HIV-infected virally suppressed children on ART (mean age 9.4 y), classified as early treated (ET; age at ART initiation ≤0.5 y, n = 14) or late treated (LT; age at ART initiation 1-10 y, n = 6). Frequencies and functions of Ag-specific CD4 (CD40L+) and CD8 (CD69+) T cells were evaluated by intracellular IL-2, IFN-γ, and TNF-α production with IL-21 in CD4 or CD107a, granzyme B and perforin in CD8 T cells following stimulation with HIV gp140 protein (ENV) or GAG peptides by multiparameter flow cytometry. ET showed a higher proportion of cytokine-producing ENV- and GAG-specific CD4 and CD8 T cells compared with LT. In particular, ET were enriched in polyfunctional T cells. RNA sequencing analysis showed upregulation of immune activation pathways in LT compared with ET. Our results suggest that timing of TI in HIV-infected children has a long-term and measurable impact on the quality of the HIV-specific T cell immune responses and transcriptional profiles of PBMC, reinforcing the importance of early TI.

Original languageEnglish (US)
Pages (from-to)540-549
Number of pages10
JournalJournal of Immunology
Volume204
Issue number3
DOIs
StatePublished - Feb 1 2020

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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    Rinaldi, S., Pallikkuth, S., Cameron, M., De Armas, L. R., Cotugno, N., Dinh, V., Pahwa, R., Richardson, B., Saini, S. R., Rocca, S., Lain, M. G., Williams, S. L., Palma, P., & Pahwa, S. (2020). Impact of early antiretroviral therapy initiation on HIV-specific CD4 and CD8 T cell function in perinatally infected children. Journal of Immunology, 204(3), 540-549. https://doi.org/10.4049/jimmunol.1900856