title: T-cell activation and neurodevelopmental outcomes in perinatally HIV-infected children.
abstract: 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.
  
  
  METHODS
  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).
  
  
  CONCLUSIONS
  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.
authors.affiliation: National Institutes of Health, National Institute Mental of Health, Bethesda, Maryland, USA. suad.kapetanovic@nih.gov
authors.forename: Suad
authors.initials: S
authors.lastname: Kapetanovic
authors.forename: Lisa
authors.initials: L
authors.lastname: Aaron
authors.forename: Grace
authors.initials: G
authors.lastname: Montepiedra
authors.forename: Sandra K
authors.initials: SK
authors.lastname: Burchett
authors.forename: Andrea
authors.initials: A
authors.lastname: Kovacs
mesh_terms: D051997:ADP-ribosyl Cyclase 1 / Q000378:metabolism; D000293:Adolescent; D023241:Antiretroviral Therapy, Highly Active; D015496:CD4-Positive T-Lymphocytes / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000378:metabolism; D002493:Central Nervous System Diseases / Q000150:complications*; D002648:Child; D002675:Child, Preschool; D005260:Female; D005500:Follow-Up Studies; D015658:HIV Infections / Q000150:complications* / Q000188:drug therapy; D006680:HLA Antigens / Q000378:metabolism; D006801:Humans; D007223:Infant; D008297:Male; D013997:Time Factors
chemical_list: D006680:HLA Antigens; D051997:ADP-ribosyl Cyclase 1