Intrinsic network connectivity abnormalities in HIV-infected individuals over age 60

Abstract

Individuals infected with HIV are living longer due to effective treatment with combination antiretroviral therapy (cART). Despite these advances, HIV-associated neurocognitive disorders (HAND) remain prevalent. In this study, we analyzed resting state functional connectivity (rs-fc) data from HIV-infected and matched HIV-uninfected adults aged 60 years and older to determine associations between HIV status, neuropsychological performance, and clinical variables. HIV-infected participants with detectable plasma HIV RNA exhibited decreased rs-fc within the salience (SAL) network compared to HIV-infected participants with suppressed plasma HIV RNA. We did not identify differences in rs-fc within HIV-infected individuals by HAND status. Our analysis identifies focal deficits in the SAL network that may be mitigated with suppression of plasma virus. However, these findings suggest that rs-fc may not be sensitive as a marker of HAND among individuals with suppressed plasma viral loads.

Chronic low-level expression of HIV-1 Tat promotes a neurodegenerative phenotype with aging

“…Structural changes in brain can persist and often worsen over time and volume reductions in multiple brain regions including grey matter, thalamus, caudate, putamen, and hippocampus have been reported 9 , 10 , 12 , 14 , 15 , 44 , 47 , 50 – 53 . Likewise, functional deficits in network connectivity have been reported in older HIV patients 54 , that are only partially resolved following the initiation of cART 55 . The mechanisms for residual neurological damage in cART treated patients is not entirely clear, but it has been repeatedly proposed to involve the long-term effects of non-structural proteins in brain that continue to be expressed despite cART.…”

Functional Connectivity in Virally Suppressed Patients with HIV-Associated Neurocognitive Disorder: A Resting-State Analysis

“…Nonetheless, in those studies with patients with HAND, 2 of 3 found a relationship to attenuation of the salience network. 10,12 Ipser et al 11 noted a relationship only with the central executive control network, but the study included patients with substance misuse and only 4 patients had HAND. Of potential additional importance is the finding by Guha et al 12 of a reduction in the salience network with an elevated plasma viral load.…”

“…10,12 Ipser et al 11 noted a relationship only with the central executive control network, but the study included patients with substance misuse and only 4 patients had HAND. Of potential additional importance is the finding by Guha et al 12 of a reduction in the salience network with an elevated plasma viral load. This may be relevant to our findings: it suggests that active HAND, at least in our study, is associated with viral replication in the brain at a level not reflected in the blood or the CSF.…”

“…We found significantly decreased connectivity in the executive and salience networks in active HAND, suggesting that it could be used as a biomarker. Furthermore, the association with the sa- lience network and its relationship with HIV replication in the blood 12 raises a further testable and plausible hypothesis: Active HAND in the context of viral suppression in blood and CSF is driven by very low-level brain replication. Future studies will need to validate these findings with larger patient numbers and correlate the findings with CSF single-copy assays of HIV.…”

“…[9][10][11][12][13] These studies have noted abnormalities, especially early in the course of HIV infection. 9 Some studies have shown conflicting results (Ipser et al 11 and Guha et al 12 ). However, no studies have been specifically designed to address the pathogenesis of HAND in the cART era.…”