Changes in Inflammation but Not in T-Cell Activation Precede Non-AIDS-Defining Events in a Case-Control Study of Patients on Long-term Antiretroviral Therapy

Angelidou, Konstantia; Hunt, Peter W.; Landay, Alan; Wilson, Cara C.; Rodríguez, Benigno; Deeks, Steven G.; Bosch, Ronald J.; Lederman, Michael M.

doi:10.1093/infdis/jix666

Cited by 29 publications

(21 citation statements)

References 35 publications

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“…If on-treatment inflammation does predict future events in this region, our data support a potentially similar benefit of ART in both earlier- and late-stage disease treatment initiators who survive and attain virologic suppression. There are suggestions from Western settings that levels of inflammation after ART initiation are potentially more predictive of future complications than pretreatment levels [13]. Similarly, our group previously reported that changes in sCD14 and the ratio of kynurenine to tryptophan (KT ratio) 6 months after treatment, but not before treatment, were predictive of increased carotid intima media thickness years later in Uganda [9] and that higher levels of KT ratio, sCD14, IL-6 and D-dimer were associated with a greater risk of mortality 6 months after ART initiation [14].…”

Section: Discussionmentioning

confidence: 99%

Timing of Antiretroviral Therapy and Systemic Inflammation in Sub-Saharan Africa: Results From the META Longitudinal Cohort Study

Siedner

Bwana

Asiimwe

et al. 2019

The Journal of Infectious Diseases

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Chronic inflammation predicts complications in persons with human immunodeficiency virus infection. We compared D-dimer, soluble CD14, and interleukin 6 levels before and 12 months after antiretroviral therapy (ART) initiation, among individuals starting ART during earlier-stage (CD4 T-cell count >350/µL) or late-stage disease (CD4 T-cell count <200/µL). Female sex, older age, viral load, and late-stage disease were associated with pre-ART biomarkers (n = 661; P < .05). However, there were no differences in biomarkers by disease stage after 12 months of ART (n = 438; P > .05), owing to loss from observation and greater declines in biomarkers in late-stage initiators (P < .001). Earlier initiation of ART is associated with decreased inflammation, but levels seem to converge between earlier and later initiators surviving to 12 months.

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Section: Discussionmentioning

confidence: 99%

Timing of Antiretroviral Therapy and Systemic Inflammation in Sub-Saharan Africa: Results From the META Longitudinal Cohort Study

Siedner

Bwana

Asiimwe

et al. 2019

The Journal of Infectious Diseases

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“…Elevated IL‐6 levels have been associated with arteriosclerosis and, in addition to hs‐CRP and d ‐dimer, with a higher risk of cardiovascular disease . Also, elevated IL‐6 and sCD14 levels were independently associated with an increased risk of mortality and changes in these biomarkers could be predictive of the emergence of non‐AIDS‐related events . In contrast, a reduction in IL‐6 and d ‐dimer levels by 25% was found to result in a 37% reduction in the rate of serious non‐AIDS‐related events/deaths .…”

Section: Discussionmentioning

confidence: 99%

Switching to dual antiretroviral regimens is associated with improvement or no changes in activation and inflammation markers in virologically suppressed HIV‐1‐infected patients: the TRILOBITHE pilot study

et al. 2019

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Objectives While the use of dual antiretroviral therapies could reduce the toxicity of antiretroviral treatment in treatment‐experienced HIV‐1‐infected patients, it is crucial to know if reducing the number of drugs could lead to an adverse increase in inflammation and activation markers. Methods This was a cross‐sectional pilot study conducted at the HIV‐1 Unit at the Tertiary University Hospital in Madrid, Spain, evaluating biomarkers of activation [interferon‐γ‐induced protein 10 (IP10), high‐sensitivity C‐reactive protein (hs‐CRP), soluble CD14 (sCD14) and sCD163], inflammation [interleukin‐6 (IL‐6)], blood coagulation (d‐dimer), and immune response [interferon (IFN)‐γ, tumour necrosis factor (TNF)‐α and IL‐4] in three groups of suppressed HIV‐1‐infected patients: patients continuing on triple therapy (26 patients), and patients who switched from triple to dual therapy, at 24 or 48 weeks after switching (13 and 36 patients, respectively). Results Demographic and immunovirological parameters were similar in the three groups of patients. IL‐6 and sCD14 levels were lower in patients at 48 weeks after switching to dual therapy compared with those found in patients who continued to receive triple therapy (P = 0.012 and P = 0.001, respectively), with no differences in the levels of the remaining biomarkers. Among patients with nadir CD4 count ≤ 200 cells/μL, sCD14 levels were lower in patients who had been on dual therapy for 48 weeks (14 patients) compared with those found in patients who received ongoing triple therapy (11 patients; P = 0.029), with no differences in the levels of the other biomarkers. Conclusions HIV‐1‐infected patients receiving dual regimens showed similar or even lower levels of inflammatory and activation markers compared with those found in patients who received ongoing triple therapy. Of note, similar data were obtained in patients with low nadir CD4 count.

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“…85 In longitudinal studies, rising levels of these biomarkers better predicted the development of NADIs than a single value at recruitment. 86 These findings suggest that impaired gut barrier function leads to the translocation of microbial products from the gut into the circulation, where they activate monocytes and macrophages, initiating a cycle of chronic inflammation. 85 This appears to be related to the activation of a specific subset of inflammatory monocytes which express Tissue Factor: these can secrete high levels of pro-inflammatory cytokines as well as trigger the coagulation cascade, so are particularly implicated in HIV-associated coagulopathy.…”

Section: Pathogenesis Of Chronic Co-morbiditiesmentioning

confidence: 99%

Chronic comorbidities in children and adolescents with perinatally acquired HIV infection in sub-Saharan Africa in the era of antiretroviral therapy

Frigati

Ameyan

Cotton

et al. 2020

The Lancet Child & Adolescent Health

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Changes in Inflammation but Not in T-Cell Activation Precede Non-AIDS-Defining Events in a Case-Control Study of Patients on Long-term Antiretroviral Therapy

Abstract: NCT00001137.

Cited by 29 publications

References 35 publications

Timing of Antiretroviral Therapy and Systemic Inflammation in Sub-Saharan Africa: Results From the META Longitudinal Cohort Study

Timing of Antiretroviral Therapy and Systemic Inflammation in Sub-Saharan Africa: Results From the META Longitudinal Cohort Study

Switching to dual antiretroviral regimens is associated with improvement or no changes in activation and inflammation markers in virologically suppressed HIV‐1‐infected patients: the TRILOBITHE pilot study

Chronic comorbidities in children and adolescents with perinatally acquired HIV infection in sub-Saharan Africa in the era of antiretroviral therapy

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