ArticlePloS one2016
Relevance of Interleukin-6 and D-Dimer for Serious Non-AIDS Morbidity and Death among HIV-Positive Adults on Suppressive Antiretroviral Therapy.
Article in PloS one, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 127 papers, 1 of them a synthesis that pooled it.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
127 citing papers in PubMed, 1 synthesis or guideline pooled it.
- Inflammatory Biomarkers Predicting Major Adverse Cardiovascular Events in People Living With HIV: A Systematic Review and Meta-Analysis.Journal of the International AIDS Society · 2026Pooled it
- Longitudinal changes in plasma biomarkers of immune activation, neuronal inflammation and injury in persons with HIV initiating ART.HIV medicine · 2026Trial
- Better Longitudinal Adherence to Antiretroviral Therapy Among Virally Suppressed People With HIV Is Associated With Reduced Occurrence of Serious Non-AIDS Events.Open forum infectious diseases · 2026Trial
- Budigalimab, an anti-PD-1 inhibitor, for people living with HIV-1: a randomized, placebo-controlled phase 1b study.Nature medicine · 2025Trial
- Changes in cerebral function parameters in persons with HIV with symptoms of insomnia switching from dolutegravir- to bictegravir-based antiretroviral therapy.Journal of neurovirology · 2025Trial
- Inflammatory Biomarker Reduction With Fostemsavir Over 96 Weeks in Heavily Treatment-Experienced Adults With Multidrug-Resistant HIV-1 in the BRIGHTE Study.Open forum infectious diseases · 2024Trial
- Brief Report: Low-Dose Methotrexate Does Not Affect Measures of HIV-1 Persistence in Individuals With Chronically Treated HIV-1 Infection.Journal of acquired immune deficiency syndromes (1999) · 2024Trial
- Changes to inflammatory markers during 5 years of viral suppression and during viral blips in people with HIV initiating different integrase inhibitor based regimens.Frontiers in immunology · 2024Trial
- Targeting the Gut Microbiota of Vertically HIV-Infected Children to Decrease Inflammation and Immunoactivation: A Pilot Clinical Trial.Nutrients · 2022Trial
- HIV is associated with an increased risk of age-related clonal hematopoiesis among older adults.Nature medicine · 2021Trial
- Clinical and Immunologic Outcomes After Immediate or Deferred Antiretroviral Therapy Initiation During Primary Human Immunodeficiency Virus Infection: The Sabes Randomized Clinical Study.Clinical infectious diseases : an official publication of the Infectious Diseases Society of America · 2021Trial
- Incomplete ART adherence is associated with higher inflammation in individuals who achieved virologic suppression in the START study.Journal of the International AIDS Society · 2019Trial
- The Effects of Recombinant Human Lactoferrin on Immune Activation and the Intestinal Microbiome Among Persons Living with Human Immunodeficiency Virus and Receiving Antiretroviral Therapy.The Journal of infectious diseases · 2019Trial
- Safety and Impact of Low-dose Methotrexate on Endothelial Function and Inflammation in Individuals With Treated Human Immunodeficiency Virus: AIDS Clinical Trials Group Study A5314.Clinical infectious diseases : an official publication of the Infectious Diseases Society of America · 2019Trial
- Vorapaxar for HIV-associated inflammation and coagulopathy (ADVICE): a randomised, double-blind, placebo-controlled trial.The lancet. HIV · 2018Trial
- Novel mediators of statin effects on plaque in HIV: a proteomics approach.AIDS (London, England) · 2018Trial
- Inflammation-Related Morbidity and Mortality Among HIV-Positive Adults: How Extensive Is It?Journal of acquired immune deficiency syndromes (1999) · 2018Trial
- Impact of early versus deferred antiretroviral therapy on estimated glomerular filtration rate in HIV-positive individuals in the START trial.International journal of antimicrobial agents · 2017Trial
- Brief Report: Changes in Levels of Inflammation After Antiretroviral Treatment During Early HIV Infection in AIDS Clinical Trials Group Study A5217.Journal of acquired immune deficiency syndromes (1999) · 2017Trial
- Trial
67 more citing papers are in PubMed but not listed here.
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Authors and funding
11 authors.
Funding
Abstract
backgroundDespite effective antiretroviral treatment (ART), HIV-positive individuals are at increased risk of serious non-AIDS conditions (cardiovascular, liver and renal disease, and cancers), perhaps due in part to ongoing inflammation and/or coagulation. To estimate the potential risk reduction in serious non-AIDS conditions or death from any cause that might be achieved with treatments that reduce inflammation and/or coagulation, we examined associations of interleukin-6 (IL-6), D-dimer, and high-sensitivity C-reactive protein (hsCRP) levels with serious non-AIDS conditions or death in 3 large cohorts.
methodsIn HIV-positive adults on suppressive ART, associations of IL-6, D-dimer, and hsCRP levels at study entry with serious non-AIDS conditions or death were studied using Cox regression. Hazard ratios (HR) adjusted for age, gender, study, and regression dilution bias (due to within-person biomarker variability) were used to predict risk reductions in serious non-AIDS conditions or death associated with lower "usual" levels of IL-6 and D-dimer.
resultsOver 4.9 years of mean follow-up, 260 of the 3766 participants experienced serious non-AIDS conditions or death. IL-6, D-dimer and hsCRP were each individually associated with risk of serious non-AIDS conditions or death, HR = 1.45 (95% CI: 1.30 to 1.63), 1.28 (95% CI: 1.14 to 1.44), and 1.17 (95% CI: 1.09 to 1.26) per 2x higher biomarker levels, respectively. In joint models, IL-6 and D-dimer were independently associated with serious non-AIDS conditions or death, with consistent results across the 3 cohorts and across serious non-AIDS event types. The association of IL-6 and D-dimer with serious non-AIDS conditions or death was graded and persisted throughout follow-up. For 25% lower "usual" IL-6 and D-dimer levels, the joint biomarker model estimates a 37% reduction (95% CI: 28 to 46%) in the risk of serious non-AIDS conditions or death if the relationship is causal.
conclusionsBoth IL-6 and D-dimer are independently associated with serious non-AIDS conditions or death among HIV-positive adults with suppressed virus. This suggests that treatments that reduce IL-6 and D-dimer levels might substantially decrease morbidity and mortality in patients on suppressive ART. Clinical trials are needed to test this hypothesis.
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