The following is a summary of “Neurocognitive Dysfunction With Neuronal Injury in People With HIV on Long-Duration Antiretroviral Therapy,” published in the June 2023 issue of Neurology by McMahan, et al.
The impact of long-duration antiretroviral therapy (ART) on neurologic outcomes in people with HIV (PWH) is poorly understood, and the underlying mechanisms are unclear. For a study, researchers sought to investigate neurocognitive and psychiatric outcomes in PWH on long-term ART compared to HIV-negative controls. Brain MRI and cerebrospinal fluid (CSF) analyses were performed to examine potential structural and biochemical differences.
Participants, including PWH on ART for at least 15 years and HIV-negative controls, underwent comprehensive neuropsychological testing, psychiatric evaluations, and optional brain MRI and CSF analysis. A novel matching technique, Coarsened Exact Matching, was employed to minimize age and sex differences between the groups. Weighted linear/logistic regression models were used to evaluate the impact of HIV on outcomes.
Data from 155 PWH on long-term ART and 100 HIV-negative controls were analyzed. Compared to controls, PWH exhibited lower performance in attention/working memory (PWH least square mean [LSM] = 50.4 vs. controls LSM = 53.1, P = 0.008), motor function (44.6 vs. 47.7, P = 0.009), and information processing speed (symbol search 30.3 vs. 32.2, P = 0.003). PWH reported a higher number of cognitive difficulties in everyday life (P = 0.011) and demonstrated higher levels of depressive symptoms, general anxiety, and use of psychiatric medications (all P < 0.05). MRI findings showed reduced proportions of subcortical gray matter in PWH (β = -0.001, P < 0.001), while CSF analysis revealed elevated levels of neurofilament light chain (664 vs. 529 pg/mL, P = 0.01) and tumor necrosis factor α (0.229 vs. 0.156 ng/mL, P = 0.0008) compared to controls.
Despite receiving effective ART for over a decade, PWH displayed neurocognitive deficits and mood abnormalities. MRI and CSF analyses indicated reduced brain volume and signs of ongoing neuronal injury and neuroinflammation. As the population of virologically controlled PWH continues to increase, longitudinal studies were needed to understand the implications of cognitive, psychiatric, MRI, and CSF abnormalities in this group.