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Updated: May 24, 2026
In Vitro Assay to Evaluate the Impact of Immunoregulatory Pathways on HIV-specific CD4 T Cell Effector Function
Published on: October 15, 2013
T-cell activation and neurodevelopmental outcomes in perinatally HIV-infected children
Suad Kapetanovic1, Lisa Aaron, Grace Montepiedra
1National Institutes of Health, National Institute Mental of Health, Bethesda, Maryland, USA. suad.kapetanovic@nih.gov
Insights
In perinatally HIV-infected children, specific T-cell activation markers (CD4+CD38+HLADR+) correlate with better neurodevelopmental outcomes, suggesting a potential neuroprotective effect in severe disease.
Area of Science:
- Immunology
- Neuroscience
- Pediatric Infectious Diseases
Background:
- Perinatally HIV-infected (PHIV) children with severe disease face risks of impaired neurodevelopment.
- T-cell activation markers are implicated in disease progression and potential neurological complications.
Purpose of the Study:
- To investigate the relationship between baseline T-cell activation and neurodevelopmental outcomes in PHIV-infected children.
- To assess changes in T-cell activation and cognitive function over a 96-week period.
Main Methods:
- Utilized data from Pediatric AIDS Clinical Trials Group protocol 366 (PACTG 366), a 96-week antiretroviral treatment study.
- Assessed neurodevelopment using standardized scales (Bayley, Wechsler).
- Analyzed T-cell activation markers (CD38, HLA-DR on CD4+ and CD8+ T cells) using linear mixed models, adjusting for multiple covariates.
Main Results:
- Higher percentages of CD4(+)CD38(+)HLADR(+) T cells were positively associated with higher full-scale Intelligence Quotient (FSIQ) scores.
- Higher percentages of CD4(+)CD38(+)HLADR(-) T cells were negatively associated with FSIQ.
- These associations were observed in a cohort of 126 PHIV-infected children with severe disease.
Conclusions:
- Elevated CD4(+)CD38(+)HLADR(+) T-cell activation may confer a neuroprotective effect in PHIV-infected children, contrasting findings in adults.
- Specific T-cell activation profiles appear to influence neurodevelopmental trajectories in this pediatric population.
Objective:
To evaluate baseline T-cell activation and neurodevelopmental outcomes over time in a cohort of perinatally HIV-infected (PHIV-infected) children with severe disease.
Design:
Pediatric AIDS Clinical Trials Group protocol 366 (PACTG 366) was a partially randomized, open-label, multicenter 96-week antiretroviral treatment-algorithm study. Neurodevelopmental status, measured by age-dependent evaluations (Bayley scales of infant development-II; Wechsler preschool and primary scale of intelligence-revised; Wechsler intelligence scale for children-III), was a secondary outcome.
Methods:
Linear mixed models were used to assess the baseline and follow-up neurodevelopmental outcomes in relation to immune activation, measured by CD38 and human leukocyte antigen (HLA) DR expression on peripheral CD4(+) and CD8(+) T cells at study baseline. Models were adjusted for age, sex, race/ethnicity, baseline viral load, baseline CD4%, cytomegalovirus (CMV) infection status at entry, study treatment arms, central nervous system penetrance score of antiretroviral regimen at entry, and viral load response 16 weeks postentry.
Results:
Among 126 PACTG 366 enrollees who were at least 1 year old and had both immune activation and age-appropriate neurodevelopmental assessments at baseline, 80 (63%) were black non-Hispanic, 71 (56%) males, 122 (97%) were on antiretrovirals, and 45 (36%) were in Centers for Disease Control and Prevention (CDC) disease category C at entry. CD4(+)CD38(+)HLADR(+)%, CD4(+)CD38(-)HLADR(+)%, and CD8(+)CD38(+)HLADR(+)% were positively associated with full-scale Intelligence Quotient scores (FSIQ) (slope = 0.18, 0.70, and 0.15, respectively; P = 0.02, 0.03, and 0.04, respectively). CD4(+)CD38(+)HLADR(-)% was negatively associated with FSIQ (slope = -0.16, P = 0.01).
Conclusion:
Contrary to HIV-infected adults, in PHIV-infected children higher CD4(+)CD38(+)HLADR(+)% may be associated with a neuroprotective effect and higher percentage of CD4(+)CD38(+) but HLADR(-) T cells may be deleterious.
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