Mapping abnormal subcortical neurodevelopment in a cohort of Thai children with HIV

Abstract

Alterations in subcortical brain structures have been reported in adults with HIV and, to a lesser extent, pediatric cohorts. The extent of longitudinal structural abnormalities in children with perinatal HIV infection (PaHIV) remains unclear. We modeled subcortical morphometry from whole brain structural magnetic resonance imaging (1.5 T) scans of 43 Thai children with PaHIV (baseline age = 11.09±2.36 years) and 50 HIV- children (11.26±2.80 years) using volumetric and surface-based shape analyses. The PaHIV sample were randomized to initiate combination antiretroviral treatment (cART) when CD4 counts were 15-24% (immediate: n = 22) or when CD4 < 15% (deferred: n = 21). Follow-up scans were acquired approximately 52 weeks after baseline. Volumetric and shape descriptors capturing local thickness and surface area dilation were defined for the bilateral accumbens, amygdala, putamen, pallidum, thalamus, caudate, and hippocampus. Regression models adjusting for clinical and demographic variables examined between and within group differences in morphometry associated with HIV. We assessed whether baseline CD4 count and cART status or timing associated with brain maturation within the PaHIV group. All models were adjusted for multiple comparisons using the false discovery rate. A pallidal subregion was significantly thinner in children with PaHIV. Regional thickness, surface area, and volume of the pallidum was associated with CD4 count in children with PaHIV. Longitudinal morphometry was not associated with HIV or cART status or timing, however, the trajectory of the left pallidum volume was positively associated with baseline CD4 count. Our findings corroborate reports in adult cohorts demonstrating a high predilection for HIV-mediated abnormalities in the basal ganglia, but suggest the effect of stable PaHIV infection on morphological aspects of brain development may be subtle.

Keywords: Brain development; MRI; Neuro HIV; Pediatric HIV; Subcortical shape analysis.

Fig. 1

Subcortical shape differences in the right pallidum between HIV+ and HIV− participants. (a) T-value map highlighting region of significantly different local thickness (RD value) associated with HIV status. (b) Boxplots of average local thickness in vertices identified as significantly different in (a).

Fig. 2

Left pallidum shape (RD top and JD bottom) associations with CD4 count within HIV+ participants. T-value maps highlighting clusters of vertices where shape is significantly associated with CD4 count; all were inversely associated (a & c). Figures b & d are scatterplots showing the average RD or JD values within significant regions plotted against participant CD4 count.

Fig. 3

Scatterplots highlighting the significant associations between baseline CD4 counts and (a) baseline left pallidum volume and (b) the change in left pallidum volume between baseline and follow-up time points. In b, red points indicate four subjects that are potentially outliers in terms of volumetric change as flagged by the interquartile range rule. The red dashed regression line is fit to the set of subjects excluding the potential outliers.