Effects of statins beyond lipid-lowering agents in ART-treated HIV infection

Frontiers in Immunology, Journal Year: 2024, Volume and Issue: 15

Published: April 9, 2024

Antiretroviral therapies (ART) have reduced human immunodeficiency virus (HIV) infection-associated morbidity and mortality improving the life of people with HIV (PWH). However, ART lead to residual production, which in conjunction microbial translocation immune dysfunction contributes chronic inflammation activation. PWH on remain at an increased risk for cardiovascular diseases (CVDs) including myocardial infarction stroke; part is explained by Lifestyle factors certain are associated dyslipidemia characterized increase low-density lipoprotein (LDL), further CVDs. Lipid-lowering agents like statins emerging as modulators decreasing a variety conditions HIV. The international randomized clinical trial REPRIEVE has shed light reduction CVDs statin therapy among PWH. Such reports indicate more than expected benefit beyond their lipid-lowering effects. Bempedoic acid, first-in-class non-statin LDL-lowering drug modulatory effects, may aid combination statins. Herein, we critically reviewed studies aimed immune-modulating roles that aging

Language: Английский

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Cytomegalovirus as an Uninvited Guest in the Response to Vaccines in People Living with HIV

Viruses, Journal Year: 2021, Volume and Issue: 13(7), P. 1266 - 1266

Published: June 29, 2021

In stark contrast to the rapid development of vaccines against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), an effective human immunodeficiency virus (HIV) vaccine is still lacking. Furthermore, despite virologic suppression and CD4 T-cell count normalization with antiretroviral therapy (ART), people living HIV (PLWH) exhibit increased morbidity mortality compared general population. Such differences in health outcomes are related higher risk behaviors, but also HIV-related immune activation viral coinfections. Among these coinfections, cytomegalovirus (CMV) latent infection a well-known inducer long-term dysregulation. Cytomegalovirus contributes persistent PLWH receiving ART by directly skewing response toward itself, increasing through modification gut microbiota microbial translocation. addition, induction immunosenescence, CMV has been associated decreased infections vaccines. This review provides comprehensive overview influence on system, mechanisms underlying reduced vaccines, discuss new therapeutic advances targeting that could be used improve PLWH.

Language: Английский

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A Two-Faced Gut Microbiome: Butyrogenic and Proinflammatory Bacteria Predominate in the Intestinal Milieu of People Living with HIV from Western Mexico

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(9), P. 4830 - 4830

Published: April 29, 2024

HIV infection results in marked alterations the gut microbiota (GM), such as loss of microbial diversity and different taxonomic metabolic profiles. Despite antiretroviral therapy (ART) partially ablating gastrointestinal alterations, profile after successful new ART has shown wide variations. Our objective was to determine GM composition functions people living with (PLWHIV) under comparison seronegative controls (SC). Fecal samples from 21 subjects (treated integrase strand-transfer inhibitors, INSTIs) 18 SC were included. We employed 16S rRNA amplicon sequencing, coupled PICRUSt2 fecal short-chain fatty acid (SCFA) quantification by gas chromatography. The INSTI group showed a decreased α-diversity (p < 0.001) compared group, at expense increased amounts Pseudomonadota (Proteobacteria), Segatella copri, Lactobacillus, Gram-negative bacteria. Concurrently, we observed an enrichment Megasphaera Butyricicoccus, both SCFA-producing bacteria, significant elevations butyrate this 0.001). Interestingly, dysbiosis PLWHIV characterized proinflammatory environment orchestrated elevated levels associated bacterial pathways, well evident presence butyrogenic role unique should be evaluated, use butyrate-based supplements regimens that contain succinate, tenofovir disoproxil succinate. This mixed is described for first time Mexico.

Language: Английский

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Gastrointestinal germinal center B cell depletion and reduction in IgA ⁺ plasma cells in HIV-1 infection

Science Immunology, Journal Year: 2024, Volume and Issue: 9(100)

Published: Oct. 25, 2024

Gastrointestinal (GI) B cells and plasma (PCs) are critical to mucosal homeostasis the host response HIV-1 infection. Here, high-resolution mapping of human PCs sampled from colon ileum during both viremic suppressed infection identified a reduction in germinal center (GC) follicular dendritic (FDCs) viremia. Immunoglobulin A-positive (IgA

Language: Английский

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Gut-dependent inflammation and alterations of the intestinal microbiota in individuals with perinatal HIV exposure and different HIV serostatus

AIDS, Journal Year: 2022, Volume and Issue: 36(14), P. 1917 - 1925

Published: July 18, 2022

HIV-exposed infected (HEI) and uninfected (HEU) children represent the two possible outcomes of maternal HIV infection. Modifications intestinal microbiome have been linked to clinical vulnerability in both settings, yet whether HEI HEU differ terms gut impairment peripheral inflammation/activation is unknown.We performed a cross-sectional, pilot study on fecal plasma as well markers damage, microbial translocation, inflammation immune activation HIV-infected born from an mother.Fecal were determined by means 16S rDNA amplification with subsequent qPCR quantification. Plasma quantified via ELISA.Forty-seven 33 consecutively enrolled. The groups displayed differences beta-diversity relative abundance, similar profiles comparable damage translocation. In contrast, monocyte (sCD14) systemic (IL-6) significantly higher than HEU.In setting perinatal infection, enduring do not appear be alterations within gut. Given that are independent predictors disease progression, future studies needed understand underlying mechanisms such processes elaborate adjuvant therapies reduce risk individuals

Language: Английский

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Honokiol hexafluoro confers reversal of neuropathological markers of HIV infection in a murine SCID model

Neurotherapeutics, Journal Year: 2024, Volume and Issue: 21(2), P. e00329 - e00329

Published: Feb. 22, 2024

Cognitive impairment remains a persistent challenge in people living with HIV (PWLH) despite antiretroviral therapy (ART) due to ART's inability eliminate brain HIV. HIV-induced cognitive dysfunction results from immune dysregulation, ongoing neuroinflammation, and the continuous virus presence, collectively contributing deficits. Therefore, adjunctive therapies are needed reduce cerebral reservoirs, mitigate impede progression. Our study focused on Honokiol, known for its anti-inflammatory neuroprotective properties, an experimental mouse model simulating dysfunction. Using Honokiol Hexafluoro (HH), synthetic analogue, we comprehensively evaluated potential ameliorate pathology HIV-associated findings showed that HH treatment effectively reversed dysfunction, concurrently suppressing astrocyte activation, restoring neuronal dendritic arborization, reducing microglial activation. Furthermore, remodeled metabolic profile of HIV-infected human monocyte-derived macrophages, resulting decreased activation promotion quiescent state vitro.

Language: Английский

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Microbial Translocation and Gut Damage Are Associated With an Elevated Fast Score in Women Living With and Without HIV

Open Forum Infectious Diseases, Journal Year: 2024, Volume and Issue: 11(5)

Published: March 28, 2024

Steatohepatitis is common in persons living with HIV and may be associated gut microbial translocation (MT). However, few studies have evaluated the gut-liver axis HIV. In Women's Interagency Study, we examined associations of circulating biomarkers linked to MT damage using FibroScan-aspartate aminotransferase (FAST) score, a noninvasive surrogate for steatohepatitis advanced fibrosis. Among 883 women 354 without HIV, used multivariable regression examine serum (kynurenine tryptophan ratio, intestinal fatty acid-binding protein, soluble CD14, CD163) log-transformed FAST score after adjusting key covariates. We path analysis mediation models determine mediating effect each biomarker on association FAST. infection was 49% higher score. levels were than (P < .001 each). mediated 13% 32% Biomarkers are mediate Our findings suggest that an important mechanism by which increases risk

Language: Английский

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HIV-1 infection is associated with depletion of germinal center B cells and a decrease in IgA⁺plasma cells in the GI tract

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: May 20, 2024

Abstract Gastrointestinal (GI) B cells and plasma (PCs) are critical to mucosal homeostasis the host response HIV-1 infection. Here, high resolution mapping of human PCs sampled from colon ileum during both viremic suppressed infection identified a reduction in germinal center (GC) follicular dendritic (FDCs) viremia. IgA + major cellular output intestinal GCs were significantly reduced PC-associated transcriptional perturbations, including type I interferon signaling, persisted antiretroviral therapy (ART)-treated individuals, suggesting ongoing disruption immune milieu ART. GI humoral perturbations associated with changes microbiome composition systemic inflammation. These findings highlight key defect mucosa due One Sentence Summary Intestinal cell linked

Language: Английский

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Immunological age prediction in HIV-infected, ART-treated individuals

Aging, Journal Year: 2021, Volume and Issue: 13(19), P. 22772 - 22791

Published: Oct. 11, 2021

Anti-retroviral therapy (ART) improves life expectancy in people living with HIV (PWH), but it remains unclear how chronic infection affects normal aging of the immune system. Plasma cell-free protein expression and phenotypes were assessed blood from ART treated PWH (19-77yrs, n = 106) age-matched, HIV-negative controls (HC, 103). Using univariate spearman correlation, we identified 277 491 age-associated parameters out a total 1,357 HC PWH, respectively. exhibited shared distinct profiles compared to highlighting effect on immunological aging. Our analysis resulted an 8-parameter, plasma-detectable inflammatory index that correlated chronological age all study participants was higher overall PWH. Additionally, predictive modeling for generated 25-parameter signature, IMAP-25, 70% 53% accuracy Applying IMAP-25 signature data revealed accelerated by 5.6 yrs. Overall, our results demonstrate signatures, easily monitored human samples, can be used as indicator one's 'immunological age' during ART-treated applied other disease states affect

Language: Английский

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The gut-microbiome contribution to HIV-associated cardiovascular disease and metabolic disorders

Current Opinion in Endocrine and Metabolic Research, Journal Year: 2021, Volume and Issue: 21, P. 100287 - 100287

Published: Oct. 27, 2021

Language: Английский

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