HIV harms children’s brains despite early ART
White matter (WM) integrity in HIV-infected children is compromised despite early antiretroviral therapy (ART) and viral load (VL) suppression, with damage persisting at 5 years of age and evidence of new damage present, a recent study has shown.
“The continued observation of clusters with lower [fractional anisotropy (FA)] and higher [mean diffusivity (MD)] in HIV-infected children point to disruptions in ongoing WM development regardless of early ART,” said the researchers.
FA in the left inferior fronto-occipital fasciulus (IFOF) and left inferior longitudinal fasciulus (ILF) were both significantly decreased in children with HIV (0.55 and 0.53, respectively) than in controls (0.62 and 0.58, respectively; p<0.001 for both). [Front Neuroanat 2017;11:88]
Across all brain regions examined, MD was significantly higher in the HIV-infected children than in controls. Of note were the differences in the left and right IFOF, left and right superior corona radiata, right forceps minor, and left and right anterior thalamic radiation (p<0.001 for all coordinates in all regions).
“These FA decreases and MD increases were largely attributable to higher RD in HIV+ children,” explained researchers, adding that the damage took place even as VL control was achieved.
“[D]espite early ART and VL suppression in 86 percent of the children by age 2 years, we continue to observe diffuse differences in WM integrity.”
In contrast, there were no observed significant differences in FA or MD across all brain regions when children who received treatment before and after 12 weeks were compared. Adjustments for treatment and interruption duration, sex and ethnicity did not significantly affect this trend.
To control for ART interruption, separate comparisons of the after-12 week group to the before-12 week children who received interrupted or continuous treatments were performed, but none reflected a potential impact of treatment timing.
The research team then compared HIV-exposed but uninfected (HEU) to HIV-unexposed and uninfected (HU) children and found significantly higher FA in the right posterior corona radiata in the HEU group than in the HU group (0.52 vs 0.44; p<0.001).
In comparison, MD in the right (0.87 vs 0.82; p<0.001) and left (0.80 vs 0.76; p<0.001) corticospinal tract was significantly higher in the HU than in the HEU group.
“The fact that treatment initiation before or after 12 weeks does not influence WM integrity at this age further suggests that WM damage occurs either very early in infection or later in development when children initiating ART before and after 12 weeks are impacted similarly,” researchers explained.
“In addition, in HEU children we find higher FA and lower MD in clusters in the CST suggesting that perinatal HIV/ART exposure has a long-term impact on WM development,” they added.