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. 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.