O48. On white matter changes in children with HIV infection and exposure

Introduction Although previous MRI studies have consistently shown immunodeficiency-related white matter (WM) alterations in humans and animal models, investigations of early development in childhood have typically included wide age ranges during which both WM volume and fractional anistropy (FA) increase significantly as part of normal development. Here, we use diffusion tensor imaging (DTI) to examine WM alterations in HIV infected children at age 7 years and compare those who initiated Antiretroviral therapy (ART) before and after 12 weeks of age. Methods POPULATION: MRI scanning was performed on 121 Xhosa and Cape Coloured 7 year old children as part of the longitudinal, neurodevelopmental Children with HIV Early Antiretroviral Therapy (CHER) trial in Cape Town, South Africa. The group included HIV-infected children who were stable on ART, and age-matched controls from the same community as part of a parallel vaccine study. After exclusion of subjects (due to motion, artifacts, etc.), we examined data from 64 HIV-infected (HIV) children and 46 uninfected controls (CTRL). SCANNING PROCEDURE: Children in the study were scanned on a 3T Siemens Allegra (Erlangen, Germany) with a single channel head coil. Children were scanned with structural T 1 imaging (MEMPRAGE) followed by 2 DTI acquisitions with opposite phase encoding (AP-PA) directions using a prospectively motion-corrected navigated twice-refocused spin echo sequence with 5 reacquisitions. Acquisition parameters for diffusion were: TR/TE = 10100/86 ms, 72 slices, voxel = 2  ×  2  ×  2 mm 3 , FOV = 224 mm, 30 non-collinear diffusion directions with b  = 1000 s/mm 2 , and four non-diffusion-weighted (b 0 ) acquisitions. Results Comparing the HIV group to CTRL, two regions in the left i nferior fronto-occipital fasciculus and left inferior longitudinal fasciculus showed lower FA, and 7 bilateral regions throughout the superior longitudinal fasciculus, superior and inferior fronto-occipital fasciculi, and left corticospinal tract showed higher MD. Conclusion Lower FA and higher MD in HIV-infected children were largely attributable to higher radial diffusivity, indicative of poorer myelination in the affected regions. Some regions with increased MD also showed increased axial diffusivity. Both axial and radial diffusivity have been shown to decrease from neonates to 1-year olds and throughout childhood. The higher levels in HIV-infected children seen here could be indicative of altered developmental trajectories.