White matter microstructure among youth with perinatally acquired HIV is associated with disease severity

Abstract

Objectives We investigated whether HIV disease severity was associated with alterations in structural brain connectivity, and whether those alterations in turn were associated with cognitive deficits in youth with perinatally-acquired HIV (PHIV). Design PHIV youth (n=40) from the Pediatric HIV/AIDS Cohort Study (PHACS) (mean age: 16±2 yrs) were included to evaluate how current and past disease severity measures (recent/nadir CD4%; peak viral load) relate to white matter (WM) microstructure within PHIV youth. PHIV youth were compared to 314 controls from the Pediatric Imaging, Neurocognition, and Genetics (PING) study. Methods Diffusion tensor imaging and tractography were utilized to assess WM microstructure. Mediation analyses were conducted to examine whether microstructure alterations contributed to relationships between higher disease severity and specific cognitive domains in PHIV youth. Results Whole brain fractional anisotropy (FA) was reduced, but radial (RD) and mean (MD) diffusivity were increased, in PHIV compared to control youth. Within PHIV youth, more severe past HIV disease was associated with reduced FA of the right inferior fronto-occipital (IFO) and left uncinate tracts; elevated MD of the F minor; and increased streamlines comprising the left inferior longitudinal fasciculus (ILF). Associations of higher peak viral load with lower working memory performance were partly mediated by reductions in right IFO FA levels. Conclusion Our findings suggest that PHIV youth have higher risk of alterations in WM microstructure compared to typically developing youth, and certain alterations are related to past disease severity. Further, WM alterations potentially mediate associations between HIV disease and working memory.

Lower total and regional grey matter brain volumes in youth with perinatally-acquired HIV infection: Associations with HIV disease severity, substance use, and cognition

“…PING youth more often than PHIV youth had caregivers who completed more than high school (72% vs 53%) and had annual household income > $30,000 (73% vs 55%) (Table 1). Forty-three percent of youth with PHIV had a CPI < 85 (more than 1 SD below norm) and average working memory scores were significantly lower than general population means of 100 (mean=87.6, p<0.001), as reported previously (Lewis-de los Angeles et al, 2016; Uban et al, 2015). At MRI scan, 85% of PHIV youth had suppressed VL (<400 copies/mL) and 92% were receiving cART (Table 1).…”

“…MRI scans were performed using standardized PING acquisition protocols (Jernigan et al, 2015; Lewis-de los Angeles et al, 2016; Uban et al, 2015) on a single 3.0 Tesla Siemens Magnetom Tim Trio scanner (Siemens Medical Solutions, Erlangen, Germany) with a 12-channel head coil. Structural MRI used a T1-weighted, MP-RAGE sequence (sagittal, TR/TE/TI=2,170/4.37/1,100ms, FOV=256x256 mm, flip angle=7 o , voxel resolution=1x1x1.2 mm 3 , scan time=8:08).…”

Early Antiretroviral Therapy in HIV-Infected Children Is Associated with Diffuse White Matter Structural Abnormality and Corpus Callosum Sparing

“…15 Regional alterations were related to past disease severity, measured by nadir CD4% and peak viral loads. 16 ART-naïve children (6-11 yrs) showed reduced myelin compared to children on ART (6-16 yrs), but were also younger. 15 These studies did not document ART history.…”

“…Lower FA, higher MD and RD in the CC and higher MD in the superior longitudinal fasciculus have been demonstrated in ART-naïve children (8-12 yrs) compared to age-matched controls 13 , while ART failure was associated with decreased FA in the left superior and right posterior corona radiata and decreased AD in the left inferior cerebellar peduncle in 50 children on first line ART (6-15 yrs). 14 Regional and whole brain decreases in FA, and increased MD and RD, compared to controls, have been reported in HIV+ children and adolescents (6-20 years) 15,16 irrespective of treatment status. 15 Regional alterations were related to past disease severity, measured by nadir CD4% and peak viral loads.…”

Contributions of Disease Severity, Psychosocial Factors, and Cognition to Behavioral Functioning in US Youth Perinatally Exposed to HIV

“…Potential mechanisms by which HIV and/or HAART impact brain development and function include neuronal injury prior to HAART, neuronal injury secondary to inflammatory responses and neurotoxic viral effects of in utero antiretroviral exposure for PHIV and PHEU youth [1, 16]. Markers of HIV disease severity are associated with white matter microstructure changes and cognitive deficits among youth with PHIV [17]. …”