Immune Activation and Inflammation in People With Human Immunodeficiency Virus: Challenging Targets.
Ontology highlight
ABSTRACT:
SUBMITTER: Utay NS
PROVIDER: S-EPMC7184903 | biostudies-literature | 2020 Apr
REPOSITORIES: biostudies-literature
Publications
Immune Activation and Inflammation in People With Human Immunodeficiency Virus: Challenging Targets.
Utay Netanya S NS Overton Edgar T ET
The Journal of infectious diseases 20200401 10
Similar Datasets
Project description:BackgroundAmong people with HIV (PWH), sex differences in presentations of atherosclerotic cardiovascular disease (ASCVD) may be influenced by differences in coronary plaque parameters, immune/inflammatory biomarkers, or relationships therein.MethodsREPRIEVE, a primary ASCVD prevention trial, enrolled antiretroviral therapy (ART)-treated PWH. At entry, a subset of US participants underwent coronary computed tomography angiography (CTA) and immune phenotyping (n = 755 CTA; n = 725 CTA + immune). We characterized sex differences in coronary plaque and immune/inflammatory biomarkers and compared immune-plaque relationships by sex. Unless noted otherwise, analyses adjust for ASCVD risk score.ResultsThe primary analysis cohort included 631 males and 124 females. ASCVD risk was higher among males (median: 4.9% vs 2.1%), while obesity rates were higher among females (48% vs 21%). Prevalence of any plaque and of plaque with either ≥1 visible noncalcified portion or vulnerable features (NC/V-P) was lower among females overall and controlling for relevant risk factors (RR [95% CI] for any plaque: .67 [.50, .92]; RR for NC/V-P: .71 [.51, 1.00] [adjusted for ASCVD risk score and body mass index]). Females showed higher levels of IL-6, hs-CRP, and D-dimer and lower levels of Lp-PLA2 (P < .001 for all). Higher levels of Lp-PLA2, MCP-1, and oxLDL were associated with higher plaque (P < .02) and NC/V-P prevalence, with no differences by sex. Among females but not males, D-dimer was associated with higher prevalence of NC/V-P (interaction P = .055).ConclusionsAmong US PWH, females had a lower prevalence of plaque and NC/V-P, as well as differences in key immune/inflammatory biomarkers. Immune-plaque relationships differed by sex for D-dimer but not other tested parameters. Clinical Trial Registration. ClinicalTrials.gov; identifier: NCT0234429 (date of initial registration: 22 January 2015).
| S-EPMC9839188 | biostudies-literature
Project description:BackgroundPersistence of viral reservoirs has been observed in people with human immunodeficiency virus (HIV), despite long-term antiretroviral therapy (ART), and likely contributes to chronic immune activation and inflammation. Obefazimod is a novel drug that inhibits human immunodeficiency virus type 1 (HIV-1) replication and reduces inflammation. Here we assess whether obefazimod is safe and might impact HIV-1 persistence, chronic immune activation, and inflammation in ART-suppressed people with HIV.MethodsWe evaluated obefazimod-related adverse events, changes in cell-associated HIV-1 DNA and RNA, residual viremia, immunophenotype, and inflammation biomarkers in blood and rectal tissue. We compared 24 ART-suppressed people with HIV who received daily doses of 50 mg obefazimod for 12 weeks (n = 13) or 150 mg for 4 weeks (n = 11) and 12 HIV-negative individuals who received 50 mg for 4 weeks.ResultsThe 50- and 150-mg doses of obefazimod were safe, although the 150-mg dose showed inferior tolerability. The 150-mg dose reduced HIV-1 DNA (P = .008, median fold change = 0.6) and residual viremia in all individuals with detectable viremia at baseline. Furthermore, obefazimod upregulated miR-124 in all participants and reduced the activation markers CD38, HLA-DR, and PD-1 and several inflammation biomarkers.ConclusionsThe effect of obefazimod by reducing chronic immune activation and inflammation suggests a potential role for the drug in virus remission strategies involving other compounds that can activate immune cells, such as latency-reversing agents.
| S-EPMC10629703 | biostudies-literature
Project description:BackgroundThe pathogenesis of hypertension (HTN) in people living with HIV/AIDS (PLHIV) is complex and remains not fully understood. Chronic immune activation (IA) is postulated to be one of the culprits. This notion is derived from studies in HIV-uninfected populations and/or animals while data on HTN and how it relates to IA in PLHIV remains scarce. We determined the relationship between HTN and IA among antiretroviral therapy (ART) naïve PLHIV.MethodsWe analysed baseline data of 365 out of 430 clinical trial participants whose main aim was to investigate the effect of low-dose aspirin on HIV disease progression in PLHIV starting ART. Soluble CD14 (sCD14), T cells co-expressing CD38 and HLA-DR, and PD-1 were the IA and exhaustion markers, respectively studied and were analysed by flow cytometry. Mann-Whitney U-test was used for comparison of the markers by HTN status. A robust Poisson regression model was used to determine the predictors for HTN.ResultsA quarter of the 365 were hypertensive (25.3%, 95% CI 20.9-29.8%), and, had higher median (IQR) body mass index (kg/m2) (23.4 (19.6, 28.0) versus 21.9 (19.3, 25.1)) and lower median (IQR) estimated glomerular filtration rate (mL/min/1.73m2) (101.2 (79.4, 126.9) versus 113.6 (92.7, 138.8)) than normotensive participants (p < 0.05). Participants with HTN had higher median frequencies of all markers of IA and exhaustion but lower sCD14 (p > 0.05). None of these markers significantly predicted the occurrence of HTN.ConclusionStudied markers of IA and exhaustion were higher in PLHIV with HTN than those without but were unpredictive of HTN. Larger multicentre studies with a wider range of markers are needed to confirm the role of IA in HIV-associated HTN.
| S-EPMC11197211 | biostudies-literature
Project description:BackgroundPersistent immune activation is thought to contribute to heightened atherosclerotic cardiovascular disease (ASCVD) risk among people with human immunodeficiency virus (PWH).MethodsParticipants (≥18 years) with or without human immunodeficiency virus (HIV) and without history of clinical ASCVD were enrolled. We hypothesized that increased macrophage-specific arterial infiltration would relate to plaque composition and systemic immune activation among PWH. We applied a novel targeted molecular imaging approach (technetium-99m [99mTc]-tilmanocept single photon emission computed tomography [SPECT]/CT) and comprehensive immune phenotyping.ResultsAortic 99mTc-tilmanocept uptake was significantly higher among PWH (n = 20) than participants without HIV (n = 10) with similar 10-year ASCVD risk (P = .02). Among PWH, but not among participants without HIV, noncalcified aortic plaque volume related directly to aortic 99mTc-tilmanocept uptake at different uptake thresholds. An interaction (P = .001) was seen between HIV status and noncalcified plaque volume, but not calcified plaque (P = .83). Systemic levels of caspase-1 (P = .004), CD14-CD16+ (nonclassical/patrolling/homing) monocytes (P = .0004) and CD8+ T cells (P = .005) related positively and CD4+/CD8+ T-cell ratio (P = .02) inversely to aortic 99mTc-tilmanocept uptake volume.ConclusionsMacrophage-specific arterial infiltration was higher among PWH and related to noncalcified aortic plaque volume only among PWH. Key systemic markers of immune activation relating to macrophage-specific arterial infiltration may contribute to heightened ASCVD risk among PWH.Clinical trials registrationNCT02542371.
| S-EPMC10205602 | biostudies-literature
Project description:Biomarkers of inflammation and immune activation were correlated with rotavirus vaccine responses in 68 human immunodeficiency virus type 1 (HIV-1)–infected (and 116 HIV-exposed but uninfected (HEU) African infants receiving pentavalent rotavirus vaccine (RV5) in a clinical trial. Prevaccination, HIV-1+ infants had significantly higher concentrations of interferon γ (IFNγ), interleukin1β, interleukin 2, interleukin 6, interleukin 10 (IL-10), and soluble CD14 compared with HEU infants. Postvaccination concentrations of neutralizing antibodies to RV5 were negatively correlated with prevaccination concentrations of IL-10 (RV5 surface proteins G1 and P1) and IFNγ (G1) in the HIV-1+ infants, whereas antirotavirus immunoglobulin A (IgA) levels were not. Heightened inflammation and immune activation in HIV-1+ infants did not alter IgA responses associated with protection from rotavirus disease.
| S-EPMC5407055 | biostudies-literature
Project description:BackgroundAtherosclerotic cardiovascular disease (CVD) is a common cause of morbidity among people with human immunodeficiency virus (PWH) who initiate antiretroviral therapy (ART). Little is known about the roles of inflammation in atherosclerotic CVD among PWH.MethodsThis cross-sectional evaluation included 178 PWH between 40 and 70 years on stable (>3 months) ART who were derived from the ongoing, prospective cohort for Comparative HIV and Aging Research in Taizhou (CHART), China, from February 2017 to August 2018. Carotid intima-media thickness (cIMT) ≥1 mm was considered as cIMT thickening indicative of atherosclerotic CVD. Plasma inflammation and coagulation biomarkers were quantified by a multiplex bead cytokine assay for 27 cytokines and enzyme-linked immunosorbent assay (ELISA) for soluble CD14 and D-dimer, respectively. We performed a series of multiparametric analyses of biomarkers and developed a composite score for atherosclerotic CVD assessment among PWH.ResultsOf 178 PWH, 53 (30.9%) had cIMT thickening. In multivariable logistic analysis adjusting for CVD and human immunodeficiency virus-specific risk factors, interleukin (IL)-4 (odds ratio [OR] = 19.0; 95% confidence interval [CI], 1.6-226.5), IL-7 (OR = 16.7; 95% CI, 1.8-151.7), IL-10 (OR = 11.9; 95% CI, 2.0-72.1), and D-dimer (OR = 3.1; 95% CI, 1.0-10.1) were significantly associated with cIMT thickening. We also developed a composite score incorporating markers (IL-7, IL-10, D-dimer, and hypertension) that accurately evaluated atherosclerotic CVD.ConclusionsThe associations of IL-4, IL-7, IL-10, and D-dimer with atherosclerosis underscores research needs to further understand the inflammatory mechanisms in the pathogenesis of atherosclerosis CVD among treated PWH. The composite score for atherosclerotic CVD assessment could be useful for risk stratification in PWH.
| S-EPMC9253881 | biostudies-literature
Project description:In a retrospective case control analysis, following adjustments for high-sensitivity C-reactive protein (hsCRP), traditional cardiovascular risk factors, and the CD4/CD8 T-cell ratio, higher lipopolysaccharide-binding protein (LBP) was associated with future myocardial infarctions in hsCRP human immunodeficiency virus (HIV). LBP may be a marker of cardiovascular risk with utility in HIV.
| S-EPMC7346757 | biostudies-literature
Project description:We evaluated immune biomarker profiles in human immunodeficiency virus (HIV)-infected adults (n = 398) from 5 African countries. Although all biomarkers decreased after antiretroviral therapy (ART) initiation, levels of C-X-C chemokine ligand 10 (CXCL10), lipopolysaccharide-binding protein, C-reactive protein, soluble CD163, and soluble scavenger receptor CD14 were significantly higher during ART than in an HIV-uninfected reference group (n = 90), indicating persistent monocyte/macrophage activation, inflammation, and microbial translocation. Before ART initiation, high HIV viral load was associated with elevated CXCL10 and tuberculosis coinfection was associated with elevated soluble CD14. High pre-ART levels of each biomarker strongly predicted residual immune activation during ART. Chemokine (C-C motif) ligand 2, lipopolysaccharide-binding protein, C-reactive protein, and interleukin 6 were differentially expressed between countries. Further research is needed on the clinical implications of residual immune dysregulation.
| S-EPMC6688057 | biostudies-literature
Project description:Plasma human immunodeficiency virus type 1 (HIV-1) RNA levels in women are lower early in untreated HIV-1 infection compared with those in men, but women have higher T-cell activation and faster disease progression when adjusted for viral load. It is not known whether these sex differences persist during effective antiretroviral therapy (ART), or whether they would be relevant for the evaluation and implementation of HIV-1 cure strategies. We prospectively enrolled a cohort of reproductive-aged women and matched men on suppressive ART and measured markers of HIV-1 persistence, residual virus activity, and immune activation. The frequency of CD4+ T cells harboring HIV-1 DNA was comparable between the sexes, but there was higher cell-associated HIV-1 RNA, higher plasma HIV-1 (single copy assay), and higher T-cell activation and PD-1 expression in men compared with women. These sex-related differences in immune phenotype and HIV-1 persistence on ART have significant implications for the design and measurement of curative interventions.
| S-EPMC6784502 | biostudies-literature
Project description:BackgroundDespite low plasma human immunodeficiency virus (HIV) RNA, HIV controllers have evidence of viral replication and elevated inflammation. We assessed the effect of antiretroviral therapy (ART) on HIV suppression, immune activation, and quality of life (QoL).MethodsA5308 was a prospective, open-label study of rilpivirine/emtricitabine/tenofovir disoproxil fumarate in ART-naive HIV controllers (N = 35), defined as having HIV RNA <500 copies/mL for ≥12 months. The primary outcome measured change in %CD38+HLA-DR+ CD8+ T cells. Residual plasma viremia was measured using the integrase single-copy assay. QoL was measured using the EQ-5D questionnaire. Outcomes were evaluated using repeated measures general estimating equations models.ResultsBefore ART, HIV controllers with undetectable residual viremia <0.6 HIV-1 RNA copies/mL had higher CD4+ counts and lower levels of T-cell activation than those with detectable residual viremia. ART use was effective in further increasing the proportion of individuals with undetectable residual viremia (pre-ART vs after 24-48 weeks of ART: 19% vs 94%, P < .001). Significant declines were observed in the %CD38+HLA-DR+CD8+ T cells at 24-48 (-4.0%, P = .001) and 72-96 (-7.2%, P < .001) weeks after ART initiation. ART use resulted in decreases of several cellular markers of immune exhaustion and in a modest but significant improvement in self-reported QoL. There were no significant changes in CD4+ counts or HIV DNA.ConclusionsART in HIV controllers reduces T-cell activation and improves markers of immune exhaustion. These results support the possible clinical benefits of ART in this population.
| S-EPMC7146008 | biostudies-literature