Association of White Matter Hyperintensities With HIV Status and Vascular Risk Factors

Abstract

Objective:To test the hypothesis that brain white matter hyperintensities (WMH) are more common in people living with HIV (PLWH), even in the setting of well-controlled infection, and to identify clinical parameters that correlate with these abnormalities.Methods:Research brain MRI scans, acquired within longitudinal studies evaluating neurocognitive outcomes, were reviewed to determine WMH load using the Fazekas visual rating scale in PLWH with well-controlled infection (antiretroviral therapy for at least one year and plasma viral-load < 200 copies/ml) and in socio-demographically-matched controls without HIV (CWOH). The primary outcome measure of this cross-sectional analysis was increased WMH load, determined by total Fazekas score ≥ 2. Multiple logistic regression analysis was performed to evaluate the effect of HIV serostatus on WMH load, and to identify MRI, CSF and clinical variables that associate with WMH in PLWH group.Results:The study included 203 PLWH and 58 CWOH who completed a brain MRI scan between April 2014 and March 2019. The multiple logistic regression analysis, with age and history of tobacco use as covariates, showed that the adjusted odds ratio of the PLWH group for increased WMH load is 3.7 (95% confidence interval 1.8–7.5, p=0.0004). For the PLWH group, increased WMH load was associated with older age, male sex, tobacco use, hypertension, and hepatitis C virus co-infection, and also with the presence of measurable tumor necrosis factor-alpha in CSF.Conclusions:Our results suggest that HIV serostatus affects the extent of brain WMH. This effect is mainly associated with aging and modifiable co-morbidities.

Increased risk for cerebral small vessel disease is associated with quantitative susceptibility mapping in HIV infected and uninfected individuals

“…Our study population shows that CSVD is more prevalent in subjects with HIV compared to controls (79% HIV+ vs. 63% HIV–) in an older population as determined by higher rates and volumes of WMHs, consistent with other studies ( Mina et al, 2021 , Moulignier et al, 2018 ). This increased prevalence of WMHs is likely driven by chronic HIV inflammation affecting the microcirculation and vascular inflammation associated with systemic vascular risk factors ( Lopez-Candales et al, 2017 , Mina et al, 2021 , Willerson and Ridker, 2004 ).…”

“…In addition to measuring WMHs as in previous studies ( Mina et al, 2021 , Moulignier et al, 2018 ), our study also used QSM to further investigate microstructural iron concentration. We found significant positive correlations between the Reynolds cardiovascular risk score and QSM in the subcortical DGM and across the entire brain in both the HIV+ and HIV– populations ( Fig.…”

Do correlates of white matter features differ between older men and women living with human immunodeficiency virus?

“…Although WMHs are imaging biomarkers of covert cerebrovascular disease frequently studied among PLWH and associated with aging and longer duration of HIV infection, 26 sex differences have been underexplored in this populatoion. 1 This pilot study expands on the existing literature by investigating the role of reproductive hormones and other risk factors as predictors of white matter disease as a function of sex within the context of HIV infection.…”

Epigenetic and integrative cross-omics analyses of cerebral white matter hyperintensities on MRI

“…Several studies have reported that people with HIV are at higher risk of an increased burden of WMH compared to uninfected controls. 142,143 Several limitations of our study must be acknowledged. First, many of our EWAS discoveries were not independently confirmed.…”