Initiation of antiretroviral therapy after the critical neuronal developmental period of the second postnatal year affects white matter microstructure in adolescents living with HIV.

Rapid maturation of major white matter pathways occurs in the first 2 years of life, indicating a critical neuronal developmental period. The impact of initiating antiretroviral therapy (ART) in children perinatally infected with HIV-1, after the age of 2 years on neurocognitive functioning and white matter development in adolescence has not been studied. Forty-six adolescents who initiated ART during the first 2 years of life (< 2 years) and 79 adolescents who initiated ART after 2 years of age (> 2 years), with perinatally acquired HIV were enrolled in the Cape Town Adolescent Antiretroviral Cohort. Adolescents completed a comprehensive neurocognitive battery testing a number of cognitive domains. Diffusion tensor imaging (DTI) was done to determine fractional anisotropy (FA), mean diffusivity (MD), axial diffusion (AD), and radial diffusion (RD) in a region of interest analysis. Neurocognitive performance was similar between adolescents who initiated ART < 2 years or > 2 years. There was a trend towards attention (p = .07) and working memory (p = .05) being poorer in the group who initiated ART > 2 years. FA was lower in the > 2-year group in the superior corona radiata (p = .03), and the external capsule (p = .04). MD was higher in the > 2-year group in the cerebral peduncle (p = .02), the superior corona radiata (p = .01), and the superior fronto-occipital fasciculus (p = .03). RD was higher in the > 2-year group in the superior corona radiata (p = .02), the cerebral peduncle (p = .01), and the superior fronto-occipital fasciculus (p = .01). However, the higher AD in the > 2-year group in the superior corona radiata was not in the expected direction (p = .01). Initiation of ART after the neuronal development period of the second postnatal year is associated with white matter alterations on neuroimaging.