TY - JOUR AU - Vieira, Vinicius AU - Lim, Nicholas AU - Singh, Alveera AU - Leitman, Ellen AU - Dsouza, Reena AU - Adland, Emily AU - Muenchhoff, Maximilian AU - Roider, Julia AU - Marin Lopez, Miguel AU - Carabelli, Julieta AU - Giandhari, Jennifer AU - Groll, Andreas AU - Jooste, Pieter AU - Prado, Julia G. AU - Thobakgale, Christina AU - Dong, Krista AU - Kiepiela, Photini AU - Prendergast, Andrew J. AU - Tudor-Williams, Gareth AU - Frater, John AU - Walker, Bruce D. AU - Ndung’u, Thumbi AU - Ramsuran, Veron AU - Leslie, Alasdair AU - Kløverpris, Henrik N. AU - Goulder, Philip T1 - Slow progression of pediatric HIV associates with early CD8+ T cell PD-1 expression and a stem-like phenotype PY - 2023/02/08/ AB - 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. JF - JCI Insight JA - JCI Insight SN - 2379-3708 DO - 10.1172/jci.insight.156049 VL - 8 IS - 3 UR - https://doi.org/10.1172/jci.insight.156049 PB - The American Society for Clinical Investigation ER -