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Published on: January 12, 2016
White Matter Abnormalities in Children with HIV Infection and Exposure
Marcin Jankiewicz1, Martha J Holmes1, Paul A Taylor2
1Division of Biomedical Engineering, Department of Human Biology, University of Cape Town, Cape Town, South Africa.
Insights
Despite early treatment, children with HIV show persistent white matter (WM) differences at age 7. This ongoing brain development impact highlights the need for continued monitoring in HIV-exposed children.
Area of Science:
- Neuroscience
- Pediatrics
- Radiology
Background:
- Combination antiretroviral therapy (ART) initiation in infancy is increasing due to updated guidelines and treatment access.
- Long-term neurodevelopmental effects of perinatal HIV infection and early ART remain understudied.
- Follow-up studies are crucial for monitoring brain development in HIV-infected (HIV+) children on ART.
Purpose of the Study:
- To investigate long-term white matter (WM) development in 7-year-old children with HIV receiving early ART.
- To compare WM integrity in HIV+ children with HIV-exposed uninfected (HEU) and HIV unexposed uninfected (HU) children.
- To assess the impact of early ART initiation on neurodevelopmental outcomes at age 7.
Main Methods:
- Diffusion tensor imaging (DTI) was used to analyze WM in 65 HIV+ and 46 control children (HEU and HU) aged 7.
- Previous findings at age 5 in corticospinal tract (CST) and longitudinal fasciculi (ILF/SLF, IFOF, UF) were re-evaluated.
- Fractional anisotropy (FA) and mean diffusivity (MD) were measured to assess WM integrity.
Main Results:
- HIV+ children exhibited lower FA in the left inferior fronto-occipital fasciculus (IFOF) and left inferior longitudinal fasciculus (ILF).
- Higher MD was observed bilaterally in the IFOF, superior corona radiata (SCR), and anterior thalamic radiation (ATR), and right forceps minor.
- Unlike at age 5, ART initiation timing did not impact WM; however, HEU children showed higher FA and lower MD in the CST compared to HU children.
Conclusions:
- Persistent WM integrity differences are observed in HIV+ children at age 7, despite early ART and viral load suppression.
- WM damage evident at age 5 persists, with new damage apparent at age 7, indicating ongoing disruptions in brain development.
- Perinatal HIV/ART exposure has a lasting impact on WM development, as suggested by findings in HEU children.
Abstract:
Background: Due to changes in guidelines and access to treatment, more children start combination antiretroviral therapy (ART) in infancy. With few studies examining the long-term effects of perinatal HIV infection and early ART on neurodevelopment, much is still unknown about brain maturation in the presence of HIV and ART. Follow-up studies of HIV infected (HIV+) children are important for monitoring brain development in the presence of HIV infection and ART. Methods: We use diffusion tensor imaging (DTI) to examine white matter (WM) in 65 HIV+ and 46 control (HIV exposed uninfected (HEU) and HIV unexposed uninfected (HU)) 7-year-old children. This is a follow up of a cohort studied at 5 years, where we previously reported lower fractional anisotropy (FA) in corticospinal tract (CST) and mean diffusivity (MD) increases in inferior/superior longitudinal fasciculi (ILF/SLF), inferior fronto-occipital fasciculus (IFOF) and uncinate fasciculus (UF) in HIV+ children compared to uninfected controls. In addition, we also found a difference in FA related to age at which ART was initiated. Results: At 7 years, we found two regions in the left IFOF and left ILF with lower FA in HIV+ children compared to controls. Higher MD was observed in a similar region in the IFOF, albeit bilaterally, as well as multiple clusters bilaterally in the superior corona radiata (SCR), the anterior thalamic radiation (ATR) and the right forceps minor. Unlike at 5 years, we found no impact on WM of ART initiation. In HEU children, we found a cluster in the right posterior corona radiata with higher FA compared to HU children, while bilateral regions in the CST demonstrated reduced MD. Conclusions: At age 7, despite early ART and viral load (VL) suppression, we continue to observe differences in WM integrity. WM damage observed at age 5 years persists, and new damage is evident. The continued observation of regions with lower FA and higher MD in HIV+ children point to disruptions in ongoing white matter development regardless of early ART. Lastly, in HEU children we find higher FA and lower MD in clusters in the CST tract suggesting that perinatal HIV/ART exposure has a long-term impact on WM development.
