Uncovering the Hidden Players <i>Double-negative T Cells in Pediatric HIV and Their Impact on Disease Progression</i>


Uşaklioğlu Erol M., Soğuksu P., Kaçmaz B. B., Meşe S., Hançerli Törün S.

PEDIATRIC INFECTIOUS DISEASE JOURNAL, cilt.45, sa.7, 2026 (SCI-Expanded, Scopus)

  • Yayın Türü: Makale / Tam Makale
  • Cilt numarası: 45 Sayı: 7
  • Basım Tarihi: 2026
  • Doi Numarası: 10.1097/inf.0000000000005199
  • Dergi Adı: PEDIATRIC INFECTIOUS DISEASE JOURNAL
  • Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus, BIOSIS, EMBASE, MEDLINE
  • İstanbul Üniversitesi Adresli: Evet

Özet

Background: Immune reconstitution in pediatric HIV infection under antiretroviral therapy (ART) is monitored by CD4(+) T-cell counts and the CD4/CD8 ratio, whereas the role of double-negative T cells (DNTs; CD3(+)CD4(-)CD8(-)) is poorly defined. We aimed to characterize CD4(+)/CD8(+) T-cell dynamics and age-dependent DNT patterns. Methods: In this retrospective cohort, 30 children were followed for 12 months after ART initiation. Flow cytometry was used to measure CD3(+), CD4(+), CD8(+) and DNT subsets and the CD4/CD8 ratio; demographic, clinical and coinfection data were abstracted from medical records. Results: The cohort comprised 30 children (20 boys, 10 girls; mean age 10.4 years). ART increased CD4(+) and decreased CD8(+) T-cell percentages, with the CD4/CD8 ratio rising from 0.73 to 1.09 and normalizing (>= 1.0) in 63.3% of children. Baseline DNT levels were elevated (mean 7.0%) but declined significantly, normalizing (<5%) in adolescents, whereas children 0-5 years maintained higher residual levels. Higher DNT percentages correlated with lower CD4(+) counts and an inverted CD4/CD8 ratio. Cytomegalovirus and Epstein-Barr virus viremia were common; in 3 children with dual cytomegalovirus/Epstein-Barr virus viremia, baseline CD4(+) percentages were lower and DNT percentages higher, and 1 had celiac disease, suggesting that dual viremia on a background of immune-mediated disease may delay immune reconstitution. DNT% reduction showed a trend toward greater decrease with integrase inhibitor-based regimens. Conclusions: In pediatric HIV infection, CD4/CD8 ratio normalization and DNT decline depict a more nuanced immune reconstitution than CD4(+) recovery alone. Age-dependent DNT trajectories support incorporating DNT monitoring as a complementary biomarker in pediatric ART management.