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.
BackgroundNeurologic outcomes in people with HIV (PWH) on long-duration antiretroviral therapy (ART) are not fully understood and the underlying pathophysiology is unclear. To address this, we established a cohort of such individuals and compared them to HIV-negative controls using a novel matching technique. Both groups underwent extensive cognitive testing, evaluation for psychiatric measures, and MRI and cerebrospinal fluid (CSF) analyses.MethodsParticipants underwent comprehensive neuropsychological (NP) testing and completed standardized questionnaires measuring depressive symptoms, perceptions of own functioning, and activities of daily living as part of an observational study. Brain MRI and lumbar puncture were optional. Coarsened Exact Matching (CEM) was used to reduce between-group differences in age and sex, and weighted linear/logistic regression models were used to assess the effect of HIV on outcomes.ResultsData were analyzed from 155 PWH on ART for at least 15 years and 100 HIV-negative controls. Compared to controls, PWH scored lower in the domains of attention/working memory (PWH Least Square Mean [LSM]=50.4 vs. controls LSM=53.1, p=0.008) and motor function (44.6 vs. 47.7, p=0.009), and a test of information processing speed (symbol search 30.3 vs. 32.2, p=0.003). They were more likely to self-report a higher number of cognitive difficulties in everyday life (p=0.011). PWH also reported more depressive symptoms, general anxiety, and use of psychiatric medications (all with p<0.05). PWH had reduced proportions of subcortical gray matter on MRI (β=-0.001, p<0.001) and CSF showed elevated levels of neurofilament-light chain (664 vs. 529 pg/mL, p=0.01) and TNF-α (0.229 vs. 0.156 ng/mL, p=0.0008).ConclusionsPWH, despite effective ART for over a decade, displayed neurocognitive deficits and mood abnormalities. MRI and CSF analyses revealed reduced brain volume and signs of ongoing neuronal injury and neuroinflammation. As the already large proportion of virologically controlled PWH continues to grow, longitudinal studies should be conducted to elucidate the implications of cognitive, psychiatric, MRI, and CSF abnormalities in this group.
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