Neurology: Impaired white matter integrity in adolescents infected with HIV during the perinatal period

Despite the efficacy of combination antiretroviral therapy (cART), adolescent patients with perinatally acquired HIV (PHIV) still exhibit cognitive dysfunction, the structural changes of which may be underlying pathophysiology.

Previous MRI studies have found smaller brain volume, higher white matter (WM) high intensity (WMH) volume, lower white matter integrity, and greater
differences in cerebral blood flow (CBF).
However, these findings may be confused with adoption status, as a large percentage of adolescents carrying PHIV are adopted
.
Adoption is associated with malnutrition and neglect, which in turn may affect brain development
.

van Genderen, Department of Pediatric Infectious Diseases, UMC Emma Children's Hospital, Amsterdam, the Netherlands, published a research article in Neuorology investigating the long-term effects of PHIV on the brain.
At the same time, the confounding effect of adoption status is minimized
.

The study included cART-treated adolescent PHIV patients and controls
matched for age, sex, ethnicity, socioeconomic status, and adoption status.
The study determined whole brain gray matter (GM) and WM volume by 3D T1-weighted scanning; Determine the total WMH volume with T2FLAIR; CBFs in the following regions of interest (ROIs) were analyzed with arterial spin labeling sequences: WM, GM, and subcortical GM ； Whole brain WM microstructural markers were analyzed using diffusion tensor imaging sequences: partial anisotropy (FA), mean diffusivity (MD), axial diffusivity (AD ), and radial diffusivity (RD)
。 Differences in neuroimaging parameters between adolescents and controls with PHIV were assessed using an age- and sex-adjusted linear regression model and applying multiple comparative corrections.

 The study included 35 adolescent PHIV patients and 38 controls with a median age of 14.
9 (IQR) : 10.
7-18.
5) and 15.
6 (IQR: 11.
1-17.
6) years, with similar adoption status
。

1.
The study found that juvenile PHIV patients had lower overall FA compared with control (beta = –0.
012; p < 0.
014, –2.
4%), MD (beta = 0.
014, p = 0.
014, 1.
3%), and RD (beta = 0.
02, p = 0.
014, 3.
3%), but no difference
in AD.

Figure 1.
Scatterplot showing WM integrity parameters for PHIV (blue) and HIV-negative matched control (red) adolescents

2.
The study found GM, WM, and WMH in ROI in adolescent PHIV patients and controls The volume is comparable
to CBF.

Table 2.
Brain volume, white matter integrity, and cerebral blood flow in adolescent PHIV patients versus controls

3.
No association
was found between cognitive characteristics and WM microstructural markers in adolescents with PHIV.

Table 3.
Correlation analysis of WM microstructure and PHIV characteristics

Despite the effectiveness of treatment, adolescents with PHIV had lower
WM integrity compared with controls, regardless of international adoption status.
These results highlight the neuropathogenic nature of HIV or, to a lesser extent, its treatment
.
Although there was no difference between groups in GM, WM, and WMH volumes and CBF in ROIs, it was because Adolescents with PHIV are often affected by cognitive impairment and experience lifelong illness and treatment, and these findings warrant follow-up
.

Original source

Brain Differences in Adolescents Living With Perinatally Acquired HIV Compared With Adoption Status Matched Controls A Cross-sectional Study.
Neurology Oct 2022, 99 (15) e1676-e1684; DOI: 10.
1212/WNL.
0000000000200946