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Markers of inflammation and activation of coagulation are associated with anaemia in antiretroviral-treated HIV disease.

ABSTRACT: The objective of this study is to determine the relationship between inflammatory interleukin-6 (IL-6) and high-sensitivity C-reactive protein (hsCRP)] and coagulation (D-dimer) biomarkers and the presence and type of anaemia among HIV-positive individuals.A cross-sectional study.Combination antiretroviral therapy (cART)-treated adults participating in an international HIV trial with haemoglobin and mean corpuscular volume (MCV) measurements at entry were categorized by presence of anaemia (haemoglobin ?14 g/dl in men and ?12 g/dl in women) and, for those with anaemia, by type [microcytic (MCV?100 fl)]. We analysed the association between inflammation (IL-6 and hsCRP) and coagulation (D-dimer) and haemoglobin, controlling for demographics (age, race and sex), BMI, HIV plasma RNA levels, CD4? T-cell counts (nadir and baseline), Karnofsky score, previous AIDS diagnosis, hepatitis B/C coinfection and use of zidovudine.Among 1410 participants, 313 (22.2%) had anaemia. Of these, 4.1, 27.2 and 68.7% had microcytic, normocytic and macrocytic anaemia, respectively. When compared with participants with normal haemoglobin values, those with anaemia were more likely to be older, black, male and on zidovudine. They also had lower baseline CD4? T-cell counts and lower Karnofsky scores. Adjusted relative odds of anaemia per two-fold higher biomarker levels were 1.22 (P?=?0.007) for IL-6, 0.99 for hsCRP (P?=?0.86) and 1.35 (P?

SUBMITTER: Borges AH

PROVIDER: S-EPMC4499102 | biostudies-literature | 2014 Jul

REPOSITORIES: biostudies-literature

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Markers of inflammation and activation of coagulation are associated with anaemia in antiretroviral-treated HIV disease.

Borges Álvaro H ÁH Weitz Jeffrey I JI Collins Gary G Baker Jason V JV Lévy Yves Y Davey Richard T RT Phillips Andrew N AN Neaton James D JD Lundgren Jens D JD Deeks Steven G SG

AIDS (London, England) 20140701 12

<h4>Objective</h4>The objective of this study is to determine the relationship between inflammatory interleukin-6 (IL-6) and high-sensitivity C-reactive protein (hsCRP)] and coagulation (D-dimer) biomarkers and the presence and type of anaemia among HIV-positive individuals.<h4>Design</h4>A cross-sectional study.<h4>Methods</h4>Combination antiretroviral therapy (cART)-treated adults participating in an international HIV trial with haemoglobin and mean corpuscular volume (MCV) measurements at en ...[more]

PMID: 25003720

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Project description:BackgroundDefining the association of non-AIDS-defining events with inflammation and immune activation among human immunodeficiency virus (HIV)-infected persons with antiretroviral therapy (ART)-associated virological suppression is critical to identifying interventions to decrease the occurrence of these events.MethodsWe conducted a case-control study of HIV-infected subjects who had achieved virological suppression within 1 year after ART initiation. Cases were patients who experienced non-AIDS-defining events, defined as myocardial infarction, stroke, non-AIDS-defining cancer, non-AIDS-defining serious bacterial infection, or death. Controls were matched to cases on the basis of age, sex, pre-ART CD4(+) T-cell count, and ART regimen. Peripheral blood mononuclear cells and plasma specimens obtained at the visit before ART initiation (hereafter, baseline), the visit approximately 1 year after ART initiation (hereafter, year 1), and the visit immediately preceding the non-AIDS-defining event (hereafter, pre-event) were analyzed for activated CD4(+) and CD8(+) T cells, plasma interleukin 6 (IL-6) level, soluble tumor necrosis factor receptor I (sTNFR-I) level, sTNFR-II level, soluble CD14 level, kynurenine-to-tryptophan (KT) ratio, and D-dimer level. Conditional logistic regression analysis was used to study the association between biomarkers and outcomes, with adjustment for potential confounders.ResultsHigher IL-6 level, sTNFR-I level, sTNFR-II level, KT ratio, and D-dimer level at year 1 were associated with the occurrence of a non-AIDS-defining event. Significant associations were also seen between non-AIDS-defining events and values of these biomarkers in specimens obtained at baseline and the pre-event time points. Effects remained significant after control for confounders. T-cell activation was not significantly related to outcomes.ConclusionsInterventional trials to decrease the incidence of non-AIDS-defining events among HIV-infected persons with virological suppression should consider targeting the pathways represented by these soluble markers. Clinical Trials Registration. NCT00001137.

Project description:The aim of the study was to explore the relationships between lymphocyte and monocyte activation, inflammation, and subclinical vascular disease among HIV-1-infected patients on antiretroviral therapy (ART).Baseline mean common carotid artery (CCA) intima-media thickness (IMT) and carotid plaque (IMT > 1.5 cm) were evaluated in the first 60 subjects enrolled in the Stopping Atherosclerosis and Treating Unhealthy Bone with Rosuvastatin in HIV (SATURN-HIV) trial. All subjects were adults on stable ART with evidence of heightened T-cell activation (CD8(+)CD38(+)HLA-DR(+) ? 19%) or increased inflammation (high-sensitivity C-reactive protein ? 2 mg/L). All had fasting low-density lipoprotein (LDL) cholesterol ? 130 mg/dL.Seventy-eight per cent of patients were men and 65% were African-American. Median (interquartile range) age and CD4 count were 47 (43, 52) years and 648 (511, 857) cells/?L, respectively. All had HIV-1 RNA < 400 HIV-1 RNA copies/mL. Mean CCA-IMT was correlated with log-transformed CD8(+)CD38(+)HLA-DR(+) percentage (r = 0.326; P = 0.043), and concentrations of interleukin-6 (r = 0.283; P = 0.028), soluble vascular cell adhesion molecule (sVCAM; r = 0.434; P = 0.004), tumour necrosis factor-? receptor-I (TNFR-I; r = 0.591; P < 0.0001) and fibrinogen (r = 0.257; P = 0.047). After adjustment for traditional cardiovascular disease (CVD) risk factors, the association with TNFR-I (P = 0.007) and fibrinogen (P = 0.033) remained significant. Subjects with plaque (n = 22; 37%) were older [mean (standard deviation) 51 (7.7) vs. 43 (9.4) years, respectively; P = 0.002], and had a higher CD8(+)CD38(+)HLA-DR(+) percentage [median (interquartile range) 31% (24, 41%) vs. 23% (20, 29%), respectively; P = 0.046] and a higher sVCAM concentration [mean (standard deviation) 737 (159) vs. 592 (160) ng/mL, respectively; P = 0.008] compared with those without plaque. Pro-inflammatory monocyte subsets and serum markers of monocyte activation (soluble CD163 and soluble CD14) were not associated with CCA-IMT or plaque.Participants in SATURN-HIV have a high level of inflammation and immune activation that is associated with subclinical vascular disease despite low serum LDL cholesterol.

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Markers of inflammation and activation of coagulation are associated with anaemia in antiretroviral-treated HIV disease.

Publications

Markers of inflammation and activation of coagulation are associated with anaemia in antiretroviral-treated HIV disease.

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