Dysfunctional Immunometabolism in HIV Infection: Contributing Factors and Implications for Age-Related Comorbid Diseases

Butterfield, Tiffany R; Landay, Alan; Anzinger, Joshua J.

doi:10.1007/s11904-020-00484-4

Cited by 22 publications

(19 citation statements)

References 155 publications

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“…Emphasis has been rightfully placed on impairments in oxidative phosphorylation in neuroHIV and degenerative diseases, such as AD 84 , 102 – 105 . The present pathway analysis underscores the potential contribution of disruptions of the TCA cycle and β-oxidation in the mitochondrial matrix, in which oxidative phosphorylation depends on the supply of reducing equivalents from the end-oxidation of nutrients 106 .…”

Section: Discussionmentioning

confidence: 99%

Central nervous system (CNS) transcriptomic correlates of human immunodeficiency virus (HIV) brain RNA load in HIV-infected individuals

Sanna

Masliah

et al. 2021

Sci Rep

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To generate new mechanistic hypotheses on the pathogenesis and disease progression of neuroHIV and identify novel therapeutic targets to improve neuropsychological function in people with HIV, we investigated host genes and pathway dysregulations associated with brain HIV RNA load in gene expression profiles of the frontal cortex, basal ganglia, and white matter of HIV+ patients. Pathway analyses showed that host genes correlated with HIV expression in all three brain regions were predominantly related to inflammation, neurodegeneration, and bioenergetics. HIV RNA load directly correlated particularly with inflammation genesets representative of cytokine signaling, and this was more prominent in white matter and the basal ganglia. Increases in interferon signaling were correlated with high brain HIV RNA load in the basal ganglia and the white matter although not in the frontal cortex. Brain HIV RNA load was inversely correlated with genesets that are indicative of neuronal and synaptic genes, particularly in the cortex, indicative of synaptic injury and neurodegeneration. Brain HIV RNA load was inversely correlated with genesets that are representative of oxidative phosphorylation, electron transfer, and the tricarboxylic acid cycle in all three brain regions. Mitochondrial dysfunction has been implicated in the toxicity of some antiretrovirals, and these results indicate that mitochondrial dysfunction is also associated with productive HIV infection. Genes and pathways correlated with brain HIV RNA load suggest potential therapeutic targets to ameliorate neuropsychological functioning in people living with HIV.

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Section: Discussionmentioning

confidence: 99%

Central nervous system (CNS) transcriptomic correlates of human immunodeficiency virus (HIV) brain RNA load in HIV-infected individuals

Sanna

Masliah

et al. 2021

Sci Rep

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“…Rising numbers of immunometabolic studies in the field of HIV-1 describe increased mitochondrial respiration in CD4 + T cells of HIV-1-infected persons with glutamine as a source for oxidative phosphorylation. These changes in immunometabolism are associated with increased expression of ROS and inflammatory cytokines, and immunometabolic dysfunction might further mediate the development of agerelated diseases (31,32). Further investigating the pathway of oxidative phosphorylation might give valuable insights into HIV-1 pathogenesis and targeting it with drugs could have a promising therapeutic potential for HIV-1-infected individuals.…”

Section: Discussionmentioning

confidence: 99%

Distinct lipid profile, low-level inflammation and increased antioxidant defense as a signature in HIV-1 elite control status

Sperk

Mikaeloff

Akusjärvi

et al. 2020

Preprint

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AbstractHIV-1 elite controllers (EC) are a rare but heterogeneous group of HIV-1-infected individuals who are able to suppress viral replication in the absence of antiretroviral therapy. The mechanisms of how EC achieve undetectable viral loads remain unclear. This study aimed to investigate host plasma metabolomics and targeted plasma proteomics in a Swedish HIV-1 cohort including EC and treatment-naïve viremic progressors (VP) as well as HIV-negative individuals (HC) to get insights into mechanisms governing EC status. Metabolites belonging to antioxidant defense had higher levels in EC relative to VP while inflammation markers were increased in VP compared to EC. Only four plasma proteins (CCL4, CCL7, CCL20, and NOS3) were increased in EC compared to HC and CCL20/CCR6 axis can play important role. Our study suggests that low-level inflammation and oxidative stress at physiological levels could be important factors contributing to control of viral replication.One Sentence SummaryHIV-1 elite controllers had a distinct lipid profile, reduced inflammation, and increased antioxidant defense that might contribute to elite control status.

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“…However, the prevalence of cardiovascular diseases (CVDs) and CVD-related mortality has increased among PLHIV, who are up to two times more likely to present a CVD episode compared with HIV-negative individuals [7][8][9] . The pathogenesis of CVD, including hypertension, in PLHIV is a complex interaction between traditional risk factors (dyslipidemia, diabetes, smoking, and sedentary lifestyle), HIV infection (viral activity, decreased TCD4+ cell count, chronic systemic inflammation, and endothelial dysfunction), and risk factors associated with HAART (dyslipidemia, endothelial damage, carotid thickness, and lipodystrophy) [10][11][12] .…”

Section: Introductionmentioning

confidence: 99%

Increased prevalence of hypertension among people living with HIV: where to begin?

Costa

Val²,

Macedo

et al. 2020

Rev. Soc. Bras. Med. Trop.

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Introduction: Cardiovascular diseases (CDVs) have become increasingly important for progressively older people living with HIV (PLHIV). Identification of gaps requiring improvement in the care cascade for hypertension, a primary risk factor for CVDs, is of utmost importance. This study analyzed the prevalence of hypertensive status and described the care cascade for hypertension screening, diagnosis, treatment, treatment adherence, and management in PLHIV. Methods: This cross-sectional study included 298 PLHIV (age >40 years) who visited a referral center in the western Brazilian Amazon. Data were collected through a structured questionnaire interview and medical examinations. Thus, information regarding sociodemographic and clinical aspects, blood pressure, weight, height, body mass index, and laboratory profile was obtained. Descriptive and analytical statistics were performed, and results were considered significant if p <0.05. Results: In total, 132 (44.3%) participants reported that their blood pressure was never measured. The prevalence of hypertension was found to be 35.9% (107/298). Of these 107 participants, only 36 (33.6%) had prior knowledge of their hypertensive status, and 19 of 36 (52.7%) participants had visited a physician or cardiologist to seek treatment. Adherence to the BP-lowering treatment was noted in 11 (10.2%) participants. Conclusions: An increased prevalence of hypertension was found, and most of the hypertensive participants were unaware of their hypertensive status. In addition, blood pressure control was poor in the study population. This indicated that public health professionals did not sufficiently consider the full spectrum of healthcare and disease management for PLHIV.

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Dysfunctional Immunometabolism in HIV Infection: Contributing Factors and Implications for Age-Related Comorbid Diseases

Cited by 22 publications

References 155 publications

Central nervous system (CNS) transcriptomic correlates of human immunodeficiency virus (HIV) brain RNA load in HIV-infected individuals

Central nervous system (CNS) transcriptomic correlates of human immunodeficiency virus (HIV) brain RNA load in HIV-infected individuals

Distinct lipid profile, low-level inflammation and increased antioxidant defense as a signature in HIV-1 elite control status

Increased prevalence of hypertension among people living with HIV: where to begin?

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