HIV-Associated Neurocognitive Disorders (HAND): The First Longitudinal Follow Up of a cART-Treated Cohort of Older People in Sub-Saharan Africa

Spooner, Rebecca; Ranasinghe, Sherika; Urasa, Sarah; Yoseph, Marcella; Koipapi, Sengua; Mukaetova‐Ladinska, Elizabeta B.; Lewis, Thomas H.; Howlett, William P.; Dekker, Marieke; Kisoli, Aloyce; Gray, William K.; Walker, Richard; Dotchin, Catherine; Kalaria, Raj N.; Lwezuala, Bingileki; Makupa, Philip C.; Akinyemi, Rufus; Paddick, Stella Maria

doi:10.2139/ssrn.3839449

Cited by 2 publications

(3 citation statements)

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“…ANI refers to the stage in which the patient's cognitive function is impaired, but it does not affect their daily life. This is a critical period during which HAND may be delayed or reversed (6). If patients are not diagnosed and intervention does not occur promptly, their cognitive ability will further decline as the disease progresses (7,8).…”

Section: Introductionmentioning

confidence: 99%

Altered regional homogeneity and functional connectivity of brain activity in young HIV-infected patients with asymptomatic neurocognitive impairment

Han

Aili

et al. 2022

Front. Neurol.

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ObjectiveAsymptomatic neurocognitive impairment (ANI) is a predominant form of cognitive impairment in young HIV-infected patients. However, the neurophysiological mechanisms underlying this disorder have not been clarified. We aimed to evaluate the altered patterns of functional brain activity in young HIV-infected patients with ANI by quantifying regional homogeneity (ReHo) and region of interest (ROI)-based functional connectivity (FC).MethodsThe experiment involved 44 young HIV-infected patients with ANI and 47 well-matched healthy controls (HCs) undergoing resting-state functional magnetic resonance imaging (rs-fMRI) and neurocognitive tests. Reho alterations were first explored between the ANI group and HC groups. Subsequently, regions showing differences in ReHo were defined as ROIs for FC analysis. Finally, the correlation of ReHo and FC with cognitive function and clinical variables was assessed.ResultsCompared with HCs, ANI patients had a significant ReHo decrease in the right lingual gyrus (LING. R), right superior occipital gyrus (SOG. R), left superior occipital gyrus (SOG. L), left middle occipital gyrus (MOG. L), right middle frontal gyrus (MFG. R), cerebellar vermis, ReHo enhancement in the left middle frontal gyrus (MFG. L), and left insula (INS L). The ANI patients showed increased FC between the LING. R and MOG. L compared to HC. For ANI patients, verbal and language scores were negatively correlated with increased mean ReHo values in the MFG.L. Increased mean ReHo values in the INS. L was positively correlated with disease duration—the mean ReHo values in the LING. R was positively correlated with the abstraction and executive function scores. Increased FC between the LING. R and MOG. L was positively correlated with verbal and language performance.ConclusionThe results suggest that the visual network might be the most vulnerable area of brain function in young HIV-infected patients with ANI. The middle frontal gyrus, cerebellar vermis, and insula also play an important role in asymptomatic neurocognitive impairment. The regional homogeneity and functional connectivity of these regions have compound alterations, which may be related to the course of the disease and neurocognitive function. These neuroimaging findings will help us understand the characteristics of brain network modifications in young HIV-infected patients with ANI.

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Section: Introductionmentioning

confidence: 99%

Altered regional homogeneity and functional connectivity of brain activity in young HIV-infected patients with asymptomatic neurocognitive impairment

Han

Aili

et al. 2022

Front. Neurol.

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“…HIV‐NCI is categorized by a spectrum of deficits, including recall memory, motor abilities, and other cognitive abilities that reduce quality of life and increase overall mortality 3 . Approximately 15–40% of PWH have some form of HIV‐NCI, and this comorbidity persists in people who are virally suppressed on ART 3–5 . There are no therapies that specifically alleviate these symptoms.…”

Section: Introductionmentioning

confidence: 99%

“…3 Approximately 15-40% of PWH have some form of HIV-NCI, and this comorbidity persists in people who are virally suppressed on ART. [3][4][5] There are no therapies that specifically alleviate these symptoms.…”

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confidence: 99%

Morphine disrupts macrophage functions even during HIV infection

Barbaro

Jaureguiberry‐Bravo

Berman

2022

Journal of Leukocyte Biology

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HIV‐associated neurocognitive impairment (HIV‐NCI) is a debilitating comorbidity that reduces quality of life in 15–40% of people with HIV (PWH) taking antiretroviral therapy (ART). Opioid use has been shown to increase neurocognitive deficits in PWH. Monocyte‐derived macrophages (MDMs) harbor HIV in the CNS even in PWH on ART. We hypothesized that morphine (MOR), a metabolite of heroin, further dysregulates functional processes in MDMs to increase neuropathogenesis. We found that, in uninfected and HIV‐infected primary human MDMs, MOR activates these cells by increasing phagocytosis and up‐regulating reactive oxygen species. Effects of MOR on phagocytosis were dependent on μ‐opioid receptor activity and were mediated, in part, by inhibited lysosomal degradation of phagocytized substrates. All results persisted when cells were treated with both MOR and a commonly prescribed ART cocktail, suggesting minimal impact of ART during opioid exposure. We then performed mass spectrometry in HIV‐infected MDMs treated with or without MOR to determine proteomic changes that suggest additional mechanisms by which opioids affect macrophage homeostasis. Using downstream pathway analyses, we found that MOR dysregulates ER quality control and extracellular matrix invasion. Our data indicate that MOR enhances inflammatory functions and impacts additional cellular processes in HIV‐infected MDMs to potentially increases neuropathogenesis in PWH using opioids.

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HIV-Associated Neurocognitive Disorders (HAND): The First Longitudinal Follow Up of a cART-Treated Cohort of Older People in Sub-Saharan Africa

Cited by 2 publications

References 0 publications

Altered regional homogeneity and functional connectivity of brain activity in young HIV-infected patients with asymptomatic neurocognitive impairment

Altered regional homogeneity and functional connectivity of brain activity in young HIV-infected patients with asymptomatic neurocognitive impairment

Morphine disrupts macrophage functions even during HIV infection

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