Factors associated to neurocognitive impairment in older adults living with HIV

Gutierrez-San-Juan, Júlia; Arrieta-Aldea, Itziar; Arnau-Barrés, Isabel; García-Escobar, G.; Lerma-Chipirraz, Elisabet; Pérez-García, Paula; Agustin, M.; Blasco-Hernando, Fabiola; González-Mena, Alicia; Cañas, Esperanza; Knobel, Hernando; Güerri‐Fernández, Robert

doi:10.1186/s40001-022-00639-6

Cited by 4 publications

(4 citation statements)

References 29 publications

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“…One such comorbidity is HIV-neurocognitive impairment (HIV-NCI), in which PWH experience a spectrum of deficits from motor dysfunction to impaired executive function. HIV-NCI greatly diminishes quality of life and increases the overall risks of morbidity and mortality [ 4 , 5 ]. Approximately 15–40% of PWH have HIV-NCI, for which there are no therapies in the ART era [ 4 , 6 , 7 ].…”

Section: Introductionmentioning

confidence: 99%

Methamphetamine Dysregulates Macrophage Functions and Autophagy to Mediate HIV Neuropathogenesis

2022

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HIV-neurocognitive impairment (HIV-NCI) can be a debilitating condition for people with HIV (PWH), despite the success of antiretroviral therapy (ART). Substance use disorder is often a comorbidity with HIV infection. The use of methamphetamine (meth) increases systemic inflammation and CNS damage in PWH. Meth may also increase neuropathogenesis through the functional dysregulation of cells that harbor HIV. Perivascular macrophages are long-lived reservoirs for HIV in the CNS. The impaired clearance of extracellular debris and increased release of reactive oxygen species (ROS) by HIV-infected macrophages cause neurotoxicity. Macroautophagy is a vital intracellular pathway that can regulate, in part, these deleterious processes. We found in HIV-infected primary human macrophages that meth inhibits phagocytosis of aggregated amyloid-β, increases total ROS, and dysregulates autophagic processes. Treatment with widely prescribed ART drugs had minimal effects, although there may be an improvement in phagocytosis when co-administered with meth. Pharmacologically inhibited lysosomal degradation, but not induction of autophagy, further increased ROS in response to meth. Using mass spectrometry, we identified the differentially expressed proteins in meth-treated, HIV-infected macrophages that participate in phagocytosis, mitochondrial function, redox metabolism, and autophagy. Significantly altered proteins may be novel targets for interventional strategies that restore functional homeostasis in HIV-infected macrophages to improve neurocognition in people with HIV-NCI using meth.

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Section: Introductionmentioning

confidence: 99%

Methamphetamine Dysregulates Macrophage Functions and Autophagy to Mediate HIV Neuropathogenesis

2022

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“…The development of effective antiretroviral therapy has increased the life expectancy of people with HIV. 1,2 The progressive spread of HIV among older adults requires constant reassessment and research. However, limited investment in primary and secondary prevention in this age group in low-and middle-income countries, in conjunction with increased life expectancy and an active sex life, are contributing to this public health problem.…”

Section: Introductionmentioning

confidence: 99%

Cognitive impairment among older adults with HIV: a systematic review protocol of cohort studies

Mahmud,

Lerner,

Rodriguez

et al. 2023

Geriatr Gerontol Aging

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Objectives: This review will determine whether the incidence of cognitive impairment in HIV patients aged ≥ 50 years is greater than that of their HIV-negative peers. Methods: The MEDLINE, EMBASE, LILACS, Web of Science, and Scopus databases will be searched for studies with a sample of individuals aged ≥ 50 years or a mixed population with ≥ 50% aged ≥ 50 years). It will include studies that evaluate seropositive patients compared to and an unexposed control group. Study design: Cohort studies with follow-up ≥ 24 months will be included. Three reviewers will independently screen for eligibility criteria, extract data, and assess the risk of bias in the included studies, as well as evaluate the overall quality of evidence. A narrative synthesis will be prepared according to synthesis without meta-analysis guidelines. Expected results: We expect to find correlations between older age, HIV, and cognitive impairment. Relevance: The association of geriatric syndromes and HIV is becoming an important field of study. Increased life expectancy accompanied by an active sex life is contributing to this public health problem. This protocol is reported according to the Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols and is registered in PROSPERO (CRD42022321914). This study was financed in part by the CAPES foundation (financial code: 001).

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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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Factors associated to neurocognitive impairment in older adults living with HIV

Cited by 4 publications

References 29 publications

Methamphetamine Dysregulates Macrophage Functions and Autophagy to Mediate HIV Neuropathogenesis

Methamphetamine Dysregulates Macrophage Functions and Autophagy to Mediate HIV Neuropathogenesis

Cognitive impairment among older adults with HIV: a systematic review protocol of cohort studies

Morphine disrupts macrophage functions even during HIV infection

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