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Normal structural brain development in adolescents treated for perinatally acquired HIV: a longitudinal imaging study
Malon Van den Hof1, Pien E J Jellema1, Anne Marleen Ter Haar1
1Emma Children's Hospital, Pediatric Infectious Diseases.
Insights
Adolescents with perinatally acquired HIV (PHIV) on long-term treatment show largely normal structural brain development over time. Follow-up MRI revealed no significant differences in white matter or grey matter volumes compared to HIV-negative peers.
Area of Science:
- Neuroscience
- Pediatrics
- Infectious Diseases
Background:
- Cross-sectional studies indicate lower brain volumes and white matter integrity in children with perinatally acquired HIV (PHIV).
- Previous research on the NOVICE cohort highlighted these structural differences in PHIV-positive children compared to controls.
Purpose of the Study:
- To longitudinally investigate changes in brain structure over time in adolescents with PHIV.
- To determine if initial differences in white matter and grey matter volumes persist or change during adolescence.
Main Methods:
- Follow-up MRI scans were conducted on participants from the NOVICE cohort after approximately 4.6 years.
- Measurements included total white matter and grey matter volume, white matter hyperintensities (WMH) volume, and white matter integrity using T1-weighted, FLAIR, and DTI sequences.
- Multivariable linear mixed effects models were used to compare rates of change between PHIV-positive and HIV-negative groups, adjusting for sex and age.
Main Results:
- No statistically significant differences in the rate of change were observed between groups for white matter volume, WMH volume, or white matter integrity.
- A trend suggested that total grey matter volume decreased significantly less in the PHIV group, but this finding lost statistical significance after adjusting for height.
- No HIV-associated determinants for reduced grey matter pruning or associations with cognitive development were identified.
Conclusions:
- Adolescents with PHIV receiving long-term antiretroviral therapy exhibit largely normal structural brain development.
- The study suggests that current treatment strategies may mitigate long-term structural brain abnormalities in this population.
Objective:
Cross-sectional studies, including one from our NOVICE cohort [Neurological Visual and Cognitive performance in children with treated perinatally acquired HIV (PHIV) compared with matched HIV-negative controls], have revealed that the brains of children with PHIV have lower white matter and grey matter volumes, more white matter hyperintensities (WMH) and poorer white matter integrity. This longitudinal study investigates whether these differences change over time.
Methods:
We approached all NOVICE participants to repeat MRI after 4.6 ± 0.3 years, measuring total white matter and grey matter volume, WMH volume and white matter integrity, obtained by T1-weighted, fluid-attenuated inversion recovery (FLAIR) and diffusion tensor imaging (DTI), respectively. We compared rates of change between groups using multivariable linear mixed effects models, adjusted for sex and age at enrolment. We investigated determinants of developmental deviation, and explored associations with cognitive development.
Results:
Twenty out of 31 (65%) PHIV-positive, and 20 out of 37 (54%) HIV-negative participants underwent follow-up MRI. Groups did not significantly differ in terms of age and sex. Over time, we found no statistically different changes between groups for white matter and WMH volumes, and for white matter integrity (P > 0.1). Total grey matter volume decreased significantly less in PHIV [group∗time 10 ml, 95% confidence interval -1 to 20, P = 0.078], but this difference in rate of change lost statistical significance after additional adjustment for height (group∗time 9 ml, 95% confidence interval -2 to 20, P = 0.112). We found no HIV-associated determinants for potential reduced grey matter pruning, nor associations with cognitive development.
Conclusion:
While using long-term antiretroviral treatment, structural brain development of adolescents growing up with perinatally acquired HIV appears largely normal.
