Changes in functional connectivity in people with HIV switching antiretroviral therapy

Toniolo, Sofia; Cercignani, Mara; Mora-Peris, Borja; Underwood, Jonathan; Alagaratnam, Jasmini; Bozzali, Marco; Boffito, Marta; Nelson, Mark; Winston, Alan; Vera, Jaime H.

doi:10.1007/s13365-020-00853-0

Cited by 11 publications

(12 citation statements)

References 46 publications

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“…The positive relationship between variability and CD4+/CD8+ ratio may also indicate the ability of temporal variability to predict the progress of HIV in the brain or the decline of CNs immune systems. Given that the CD4+/CD8+ ratio is a more accurate hallmark of the status of the body immune system ( 93 , 94 ), we speculate that monitoring of trends of the CN CD4+/CD8+ ratio balance on differential antiretroviral therapies can be achieved through tracking the temporal variability, supporting earlier studies detecting functional changes with switching antiretroviral drugs ( 17 ). Again, since cART repairs innate CNs by reducing inflammation and enhances synoptodentritic plasticity that improves dynamic synaptic communication and neural functions ( 4 , 95 ), we hypothesize that the observed variability increases in HIV patients on stable cART might also be attributed to cART stabilization; however, further evidence is required to confirm this supposition.…”

Section: Discussionsupporting

confidence: 78%

“…Alterations of striato-cortical regional activities (ReHo) and amplitude of low-frequency fluctuations (ALFF) relating to patients' CD4+T-cell counts and waning cognitive learning and memory have also been reported ( 15 , 16 ). Studies of asymptomatic HIV patients, however, have reported that antiretroviral drugs could delay or improve brain activity ( 17 ). For example, switching from efavirenz to rilpivirine appeared to improve functional connectivity of the dorsal attention network along with enhancing working memory, speed of visual processing, and executive function while switching from raltegravir to dolutegravir appeared to improve the dorsal attention and associative visual and sensory-motor networks ( 17 ).…”

Section: Introductionmentioning

confidence: 99%

“…Studies of asymptomatic HIV patients, however, have reported that antiretroviral drugs could delay or improve brain activity ( 17 ). For example, switching from efavirenz to rilpivirine appeared to improve functional connectivity of the dorsal attention network along with enhancing working memory, speed of visual processing, and executive function while switching from raltegravir to dolutegravir appeared to improve the dorsal attention and associative visual and sensory-motor networks ( 17 ). Studies have also suggested that assessing functional interactions of multiple regions could reveal more brain changes underlying brain functionality losses in HIV patients ( 18 ).…”

Section: Introductionmentioning

confidence: 99%

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Atypical Resting-State Functional Connectivity Dynamics Correlate With Early Cognitive Dysfunction in HIV Infection

et al. 2021

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Purpose: Previous studies have shown that HIV affects striato-cortical regions, leading to persisting cognitive impairment in 30–70% of the infected individuals despite combination antiretroviral therapy. This study aimed to investigate brain functional dynamics whose deficits might link to early cognitive decline or immunologic deterioration.Methods: We applied sliding windows and K-means clustering to fMRI data (HIV patients with asymptomatic neurocognitive impairment and controls) to construct dynamic resting-state functional connectivity (RSFC) maps and identify states of their reoccurrences. The average and variability of dynamic RSFC, and the dwelling time and state transitioning of each state were evaluated.Results: HIV patients demonstrated greater variability in RSFC between the left pallidum and regions of right pre-central and post-central gyri, and between the right supramarginal gyrus and regions of the right putamen and left pallidum. Greater variability was also found in the frontal RSFC of pars orbitalis of the left inferior frontal gyrus and right superior frontal gyrus (medial). While deficits in learning and memory recall of HIV patients related to greater striato-sensorimotor variability, deficits in attention and working memory were associated with greater frontal variability. Greater striato-parietal variability presented a strong link with immunologic function (CD4+/CD8+ ratio). Furthermore, HIV-infected patients exhibited longer time and reduced transitioning in states typified by weaker connectivity in specific networks. CD4+T-cell counts of the HIV-patients were related to reduced state transitioning.Conclusion: Our findings suggest that HIV alters brain functional connectivity dynamics, which may underlie early cognitive impairment. These findings provide novel insights into our understanding of HIV pathology, complementing the existing knowledge.

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Section: Discussionsupporting

confidence: 78%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Atypical Resting-State Functional Connectivity Dynamics Correlate With Early Cognitive Dysfunction in HIV Infection

et al. 2021

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“…A smaller clinical study of patients with controlled infection reported changes in salience and executive networks that correlated with neuropsychological test scores [ 26 ]. Other evidence suggests that during acute HIV infection, changes in resting-state functional connectivity in several brain regions correlate with depressive symptoms [ 27 ], and switching ART regimens may affect functional connectivity in asymptomatic patients [ 28 ]. Thus, functional connectivity appears to be altered in HAND patients with controlled infection and may correlate with cognitive impairment as well as other auxiliary symptoms of HAND.…”

Section: Neuroimaging and Neuropathological Studies In Hand Patientsmentioning

confidence: 99%

Mechanisms of neuronal dysfunction in HIV-associated neurocognitive disorders

Irollo

Luchetta

et al. 2021

Cell. Mol. Life Sci.

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HIV-associated neurocognitive disorder (HAND) is characterized by cognitive and behavioral deficits in people living with HIV. HAND is still common in patients that take antiretroviral therapies, although they tend to present with less severe symptoms. The continued prevalence of HAND in treated patients is a major therapeutic challenge, as even minor cognitive impairment decreases patient’s quality of life. Therefore, modern HAND research aims to broaden our understanding of the mechanisms that drive cognitive impairment in people with HIV and identify promising molecular pathways and targets that could be exploited therapeutically. Recent studies suggest that HAND in treated patients is at least partially induced by subtle synaptodendritic damage and disruption of neuronal networks in brain areas that mediate learning, memory, and executive functions. Although the causes of subtle neuronal dysfunction are varied, reversing synaptodendritic damage in animal models restores cognitive function and thus highlights a promising therapeutic approach. In this review, we examine evidence of synaptodendritic damage and disrupted neuronal connectivity in HAND from clinical neuroimaging and neuropathology studies and discuss studies in HAND models that define structural and functional impairment of neurotransmission. Then, we report molecular pathways, mechanisms, and comorbidities involved in this neuronal dysfunction, discuss new approaches to reverse neuronal damage, and highlight current gaps in knowledge. Continued research on the manifestation and mechanisms of synaptic injury and network dysfunction in HAND patients and experimental models will be critical if we are to develop safe and effective therapies that reverse subtle neuropathology and cognitive impairment.

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“… 20 To our knowledge, there are no previous studies linking fMRI networks and sleep quality in the HIV-infected population. However, it has been noted that changes in functional connectivity are seen when switching cART medications, 21 especially in the attention networks. Furthermore, patients with HIV-associated cognitive impairment show remodeling of the DMN.…”

Section: Introductionmentioning

confidence: 99%

Functional MRI Correlates of Sleep Quality in HIV

Venkataraman

Zhuang

Marsella

et al. 2021

NSS

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Objective: To examine resting-state functional MRI (rs-fMRI) networks related to sleep in the context of HIV infection. Methods: rs-fMRI data were collected in 40 HIV-infected (HIV+) individuals at baseline (treatment-naive), 12 week (post-treatment) and one year timepoints. A group of 50 agematched HIV-negative (HIV-) individuals were also imaged at baseline and one year timepoints. The Pittsburgh Sleep Quality Index (PSQI) questionnaire was administered at all timepoints. Using group independent component analysis (ICA), maps of functional networks were generated from fMRI data; from these, sleep-related networks were selected. A generalized linear model (GLM) was used to analyze if these networks were significantly associated with the PSQI score, and if this relationship was influenced by HIV status/ treatment or timepoint. Results: HIV+ individuals had significantly lower PSQI score after treatment (p=0.022). Networks extracted from group ICA analysis included the anterior and posterior default mode network (DMN), central executive network (CEN), bilateral frontoparietal networks (FPNs), and the anterior cingulate cortex salience network (ACC SN). We found the posterior DMN, right FPN, and ACC SN GLMs showed significantly higher goodness-of-fit after incorporating PSQI data (p = 0.0204, 0.044, 0.044, respectively). Furthermore, the correlation between ACC SN and posterior DMN connectivity was significantly decreased in the HIV+ cohort. Conclusion:Functional networks such as the DMN, FPN, CEN, and ACC SN are altered in poor sleep, as measured by the PSQI score. Furthermore, the relationship between these networks and PSQI is different in the HIV+ and HIV-populations.

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Changes in functional connectivity in people with HIV switching antiretroviral therapy

Cited by 11 publications

References 46 publications

Atypical Resting-State Functional Connectivity Dynamics Correlate With Early Cognitive Dysfunction in HIV Infection

Atypical Resting-State Functional Connectivity Dynamics Correlate With Early Cognitive Dysfunction in HIV Infection

Mechanisms of neuronal dysfunction in HIV-associated neurocognitive disorders

Functional MRI Correlates of Sleep Quality in HIV

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