Early Antiretroviral Therapy Reduces Severity but Does Not Eliminate Neurodevelopmental Compromise in Children With HIV

Abstract

Background: Early antiretroviral therapy (ART) during infancy reduces cognitive impairment due to HIV, but the extent of benefit is unclear. Setting: Children were recruited from hospital and health centers providing HIV care and treatment in Nairobi, Kenya. Methods: Cognitive, behavioral, and motor outcomes were assessed in children with HIV and early ART (<1 year), children with HIV and late ART (1.5–6 years), and children HIV–unexposed uninfected (CHUU). Domain z scores and odds neurobehavioral impairment (≤15th percentile in CHUU) were compared in adjusted analyses. Results: Children with HIV initiated ART at median ages 0.4 (early ART) and 3.5 years (late ART). Children were assessed at median ages 6.9 (CHUU, N = 61), 6.9 (early ART, N = 54), and 13.5 (late ART; N = 27) years. Children with late ART vs. children with early ART had significantly lower z scores in 7 domains, specifically global cognition, short-term memory, visuospatial processing, learning, nonverbal test performance, executive function, and motor skills (adjusted mean differences, −0.42 to −0.62, P values ≤ 0.05), and had higher odds impairment in 7 domains (adjusted odds ratios [aORs], 2.87 to 16.22, P values ≤ 0.05). Children with early ART vs. CHUU had lower z scores in 5 domains (global cognition, short-term memory, delayed memory, processing speed, and behavioral regulation [adjusted mean differences, −0.32 to −0.88, P values < 0.05]) and higher impairment for 2 domains (short-term memory [aOR, 3.88] and behavioral regulation [aOR 3.46], P values < 0.05). Children with late ART vs. CHUU had lower z scores in 8 domains (adjusted mean differences, −0.57 to −1.05, P values ≤ 0.05), and higher impairment in 7 domains (aORs 1.98 to 2.32, P values ≤ 0.05). Conclusion: Early ART in the first year of life attenuates but does not eliminate the neurodevelopmental compromise of HIV.