Brain Differences in Adolescents Living With Perinatally Acquired HIV Compared With Adoption Status Matched Controls A Cross-sectional Study

Background and Objectives Despite effective combination antiretroviral therapy (cART), adolescents with perinatally acquired HIV (PHIV) exhibit cognitive impairment, of which structural changes could be the underlying pathophysiologic mechanism. Prior MRI studies found lower brain volumes, higher white matter (WM) hyperintensity (WMH) volume, lower WM integrity, and differences in cerebral blood flow (CBF). However, these findings may be confounded by adoption status, as a large portion of adolescents with PHIV have been adopted. Adoption has been associated with malnutrition and neglect, which, in turn, may have affected brain development. We investigated the long-term effects of PHIV on the brain, while minimizing the confounding effect of adoption status. Methods We determined whole-brain gray matter (GM) and WM volume with 3D T1-weighted scans; total WMH volume with fluid-attenuated inversion recovery; CBF in the following regions of interest (ROIs): WM, GM, and subcortical GM with arterial spin labeling; and whole-brain WM microstructural markers: fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (AD), and radial diffusivity (RD) with diffusion tensor imaging in cART-treated adolescents with PHIV visiting our outpatient clinic in Amsterdam and controls matched for age, sex, ethnic origin, socioeconomic status, and adoption status. We assessed differences in neuroimaging parameters between adolescents with PHIV and controls using linear regression models adjusted for age and sex and applied multiple comparison correction. Results Thirty-five adolescents with PHIV and 38 controls were included with a median age of 14.9 (interquartile range [IQR]: 10.7-18.5) and 15.6 (IQR: 11.1-17.6) years, respectively, with a similar rate of adoption. We found a lower overall FA (beta = -0.012; p < 0.014, -2.4%), a higher MD (beta = 0.014, p = 0.014, 1.3%), and a higher RD (beta = 0.02, p = 0.014, 3.3%) in adolescents with PHIV vs adoption-matched controls, but no differences in AD. We found comparable GM, WM, and WMH volume and CBF in ROIs between adolescents with PHIV and controls. We did not find an association between cognitive profiles and WM microstructural markers in adolescents with PHIV. Discussion Irrespective of adoption status, adolescents with PHIV exhibited subtle lower WM integrity. Our findings may point toward early-acquired WM microstructural alterations associated with HIV.

Automated summary

Despite adoption status potentially affecting brain development, adolescents with perinatally acquired HIV still exhibit subtle lower white matter integrity.