Abstract
Cerebral white matter hyperintensities (WMH) persist in children and adults living with HIV, despite effective combination antiretroviral therapy (cART). As age and principal routes of transmission differ between children (perinatally) and adults (behaviorally), comparing the characteristics and determinants of WMH between these populations may increase our understanding of the pathophysiology of WMH. From separate cohorts of 31 children (NOVICE) and 74 adults (AGEhIV), we cross-sectionally assessed total WMH volume and number of WMH per location (periventricular vs. deep) using fluid-attenuated inversion recovery (FLAIR) MRI images. WMH were either periventricular when within 10mm of the lateral ventricles, or deep otherwise. We assessed patient- or HIV-related determinants of total WMH volume (adjusted for intracranial volume) and location of WMH using logistic regression, while stratifying on children and adults. At enrollment, median age of participants was 13.8 years (IQR 11.4–15.9) for children and 53.4 years (IQR 48.3–60.8) for adults and 27/31 children (87%) and 74/74 adults (100%) had an HIV RNA viral load <200 copies/mL. WMH were present in 16/27 (52%) children and 74/74 adults (100%). The prevalence of deep WMH was not different between groups, (16/16 [100%] in children vs. 71/74 [96%] in adults, p = 0,999), yet periventricular WMH were more prevalent in adults (74/74 [100%]) compared to children (9/16; 56%) (p<0.001). Median WMH volume was higher in adults compared to children (1182 mm3 [425–2617] vs. 109 mm3 [61.7–625], p<0.001). In children, boys were more likely to have deep WMH compared to girls. In adults, older age was associated with higher total WMH volume, and age, hypertension and lower CD4+ T-lymphocyte nadir with a higher number of periventricular WMH. Our findings suggest that the location of WMH differs between children and adults living with HIV, hinting at a different underlying pathogenesis.
Highlights
The widespread use of combination antiretroviral therapy has resulted in a substantial decline in the incidence of severe HIV-related neurological complications, including HIVencephalopathy in children with perinatally acquired HIV infection (PHIV) and HIV-associated dementia in adults with behaviorally acquired HIV infection [1, 2].Cerebral white matter hyperintensities (WMH) have been reported to be more prevalent in children and adults living with HIV on effective cART compared to their respective healthy controls [3,4,5]
To increase pathophysiological understanding of cerebral WMH in people living with HIV, we explored their possible relationship with age and mode of HIV acquisition, by comparing the presence, size and location of WMH between our ongoing cohort studies of children and adults living with HIV
The following exclusion criteria had been used for both cohorts: current or past neurological or psychiatric disorders not associated with HIV, a history of traumatic brain injury resulting a loss of consciousness of more than 30 minutes, intracerebral neoplasms and Magnetic Resonance Imaging (MRI) contraindications including metal implants or claustrophobia; the complete criteria for noninclusion have been previously published in detail [3, 5]
Summary
Cerebral white matter hyperintensities (WMH) have been reported to be more prevalent in children and adults living with HIV on effective cART compared to their respective healthy controls [3,4,5]. WMH are associated with poorer cognitive performance, namely attention and learning as compared to adults without HIV [6, 7], which may lead to poorer cART adherence and increased need of social services [8, 9]. Studies of brain structure and function, including those addressing WMH, are limited in children on cART [13]. Without a controlled comparison, reported a 50% prevalence of WMH in a group of children who were investigated because of suspected HIV-related brain disease [16]
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