Slow progression of pediatric HIV associates with early CD8+ T cell PD-1 expression and a stem-like phenotype

JCI Insight. 2023 Feb 8;8(3):e156049. doi: 10.1172/jci.insight.156049.


HIV nonprogression despite persistent viremia is rare among adults who are naive to antiretroviral therapy (ART) but relatively common among ART-naive children. Previous studies indicate that ART-naive pediatric slow progressors (PSPs) adopt immune evasion strategies similar to those described in natural hosts of SIV. However, the mechanisms underlying this immunophenotype are not well understood. In a cohort of early-treated infants who underwent analytical treatment interruption (ATI) after 12 months of ART, expression of PD-1 on CD8+ T cells immediately before ATI was the main predictor of slow progression during ATI. PD-1+CD8+ T cell frequency was also negatively correlated with CCR5 and HLA-DR expression on CD4+ T cells and predicted stronger HIV-specific T lymphocyte responses. In the CD8+ T cell compartment of PSPs, we identified an enrichment of stem-like TCF-1+PD-1+ memory cells, whereas pediatric progressors and viremic adults had a terminally exhausted PD-1+CD39+ population. TCF-1+PD-1+ expression on CD8+ T cells was associated with higher proliferative activity and stronger Gag-specific effector functionality. These data prompted the hypothesis that the proliferative burst potential of stem-like HIV-specific cytotoxic cells could be exploited in therapeutic strategies to boost the antiviral response and facilitate remission in infants who received early ART with a preserved and nonexhausted T cell compartment.

Keywords: AIDS/HIV; Adaptive immunity; Immunology; T cells.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • CD4-Positive T-Lymphocytes
  • CD8-Positive T-Lymphocytes
  • HIV Infections*
  • Humans
  • Phenotype
  • Programmed Cell Death 1 Receptor* / metabolism


  • Programmed Cell Death 1 Receptor
  • PDCD1 protein, human