Getting to the point: Methamphetamine injection is associated with biomarkers relevant to HIV pathogenesis

Miller, Michelle; Lee, Ji Young; Fulcher, Jennifer A.; Roach, Margaret; Dilworth, Samantha E.; Chahine, Antonio; Pallikkuth, Suresh; Fuchs, Dietmar; Pahwa, Savita

doi:10.1016/j.drugalcdep.2020.108133

Cited by 14 publications

(13 citation statements)

References 36 publications

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“…This suggests that gene expression-related mechanisms may explain the existing in vitro data demonstrating that meth pre-treatment can enhance HIV infection [ 48 , 91 ]. Our data similarly highlight an interaction between meth and HIV in infected macrophage reservoirs that could mediate clinical findings of higher inflammatory markers in meth using PWH [ 13 ]. Proteins associated with neurodegenerative diseases, such as Alzheimer’s and Parkinson’s, were significantly enriched.…”

Section: Discussionsupporting

confidence: 61%

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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: Discussionsupporting

confidence: 61%

“…A 2020 study of 351 PWH found that non-adherence to ART was ~18% higher in people who reported meth use. A recent analysis of PWH reporting meth use demonstrated higher serum levels of the inflammatory mediators, IL-6 and sD163, than in people not using meth [ 13 ]. This suggests that meth may directly impact immune cells.…”

Section: Introductionmentioning

confidence: 99%

Methamphetamine Dysregulates Macrophage Functions and Autophagy to Mediate HIV Neuropathogenesis

2022

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“…Bearing in mind that stimulants act primarily by altering the function of catecholamines, stimulants and HIV are independently associated with higher NE in cerebrospinal fluid and dysregulated systemic metabolism of tyrosine (an essential amino acid precursor for catecholamines) (141,142). Alterations in catecholamines could partially explain associations of stimulant use with greater immune activation, inflammation, HIV proviral DNA in immune cells, and immune exhaustion in PWH who are virally suppressed or undetectable (142)(143)(144)(145)(146). Interestingly, the associations of stimulant use with these outcomes often persist after adjusting for self-reported ART adherence (142)(143)(144)(145)(146).…”

Section: Neuroendocrine Signaling and The Microbiome-gut-brain Axismentioning

confidence: 99%

Through the Looking-Glass: Psychoneuroimmunology and the Microbiome-Gut-Brain Axis in the Modern Antiretroviral Therapy Era

et al. 2022

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Objective: Depression, substance use disorders, and other neuropsychiatric comorbidities are common in people with HIV (PWH), but the underlying mechanisms are not sufficiently understood. HIV-induced damage to the gastrointestinal tract potentiates residual immune dysregulation in PWH receiving effective antiretroviral therapy. However, few studies among PWH have examined the relevance of microbiomegut-brain axis: bidirectional crosstalk between the gastrointestinal tract, immune system, and central nervous system. Methods: A narrative review was conducted to integrate findings from 159 articles relevant to psychoneuroimmunology (PNI) and microbiome-gut-brain axis research in PWH. Results: Early PNI studies demonstrated that neuroendocrine signaling via the hypothalamic-pituitary-adrenal axis and autonomic nervous system could partially account for the associations of psychological factors with clinical HIV progression. This review highlights the need for PNI studies examining the mechanistic relevance of the gut microbiota for residual immune dysregulation, tryptophan catabolism, and oxytocin release as key biological determinants of neuropsychiatric comorbidities in PWH (i.e., body-to-mind pathways). It also underscores the continued relevance of neuroendocrine signaling via the hypothalamic-pituitary-adrenal axis, autonomic nervous system, and oxytocin release in modifying microbiome-gut-brain axis functioning (i.e., mind-to-body pathways). Conclusions: Advancing our understanding of PNI and microbiome-gut-brain axis pathways relevant to depression, substance use disorders, and other neuropsychiatric comorbidities in PWH can guide the development of novel biobehavioral interventions to optimize health outcomes. Recommendations are provided for biobehavioral and neurobehavioral research investigating bidirectional PNI and microbiomegut-brain axis pathways among PWH in the modern antiretroviral therapy era.

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“…The deleterious consequences of stimulant use for HIV pathogenesis are supported partially by mechanistic studies documenting its direct and indirect effects on immune function (29,30). Several recent cross-sectional studies in those with treated HIV highlight that stimulant use could potentiate immune activation, inflammation, HIV persistence, and immunosenescence (31)(32)(33)(34)(35). Methamphetamine-induced alterations in these pathophysiologic processes could accelerate cellular aging.…”

Section: Introductionmentioning

confidence: 99%

Sexual Minority Stress and Cellular Aging in Methamphetamine-Using Sexual Minority Men With Treated HIV

et al. 2022

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Objective: Sexual minority men (e.g., gay, bisexual, and other men who have sex with men) experience stigma and sexual minority stress, which are theorized to drive negative health outcomes. Sexual minority men with treated HIV display persistent immune dysregulation, which could be amplified by sexual minority stress responses to potentiate cellular aging. Methods: This cross-sectional study included 52 sexual minority men living with HIV who had undetectable viral load (<40 copies/mL) and biologically confirmed recent methamphetamine use. Participants completed measures assessing sexual minority stress and openness about sexual minority status (i.e., outness). DNA methylation-derived outcomes included the following: the extrinsic epigenetic age acceleration clock, telomere length, naive CD4+ T-helper cells, and naive CD8+ T-cytotoxic/suppressor cells. Results: After adjusting for negative affect and recent stimulant use, higher sexual minority stress was associated with a faster extrinsic epigenetic age acceleration clock (β = 0.29, p = .030), shorter telomere length (β = −0.43, p = .002), and fewer naive CD4+ (β = −0.57, p < .001) and naive CD8+ T cells (β = −0.57, p < .001). Greater outness was associated with higher naive CD4+ (β = 0.32, p = .030) and naive CD8+ T cells (β = 0.38, p = .008) as well as lower plasma interleukin 6 (β = −0.33, p = .027). Conclusions: Sexual minority stress processes are associated with markers of cellular aging and inflammation in methamphetamine-using sexual minority men living with HIV. Longitudinal research should elucidate biobehavioral mechanisms linking sexual minority stress processes with accelerated cellular aging in those with and without HIV.

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Getting to the point: Methamphetamine injection is associated with biomarkers relevant to HIV pathogenesis

Cited by 14 publications

References 36 publications

Methamphetamine Dysregulates Macrophage Functions and Autophagy to Mediate HIV Neuropathogenesis

Methamphetamine Dysregulates Macrophage Functions and Autophagy to Mediate HIV Neuropathogenesis

Through the Looking-Glass: Psychoneuroimmunology and the Microbiome-Gut-Brain Axis in the Modern Antiretroviral Therapy Era

Sexual Minority Stress and Cellular Aging in Methamphetamine-Using Sexual Minority Men With Treated HIV

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