Relevance of Interleukin-6 and D-Dimer for Serious Non-AIDS Morbidity and Death among HIV-Positive Adults on Suppressive Antiretroviral Therapy.
<h4>Background</h4>Despite 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 poten...
| Main Authors: | , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2016-01-01
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| Series: | PLoS ONE |
| Online Access: | https://doi.org/10.1371/journal.pone.0155100 |
| _version_ | 1819145169296949248 |
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| author | Birgit Grund Jason V Baker Steven G Deeks Julian Wolfson Deborah Wentworth Alessandro Cozzi-Lepri Calvin J Cohen Andrew Phillips Jens D Lundgren James D Neaton INSIGHT SMART/ESPRIT/SILCAAT Study Group |
| author_facet | Birgit Grund Jason V Baker Steven G Deeks Julian Wolfson Deborah Wentworth Alessandro Cozzi-Lepri Calvin J Cohen Andrew Phillips Jens D Lundgren James D Neaton INSIGHT SMART/ESPRIT/SILCAAT Study Group |
| author_sort | Birgit Grund |
| collection | DOAJ |
| description | <h4>Background</h4>Despite 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.<h4>Methods</h4>In 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.<h4>Results</h4>Over 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.<h4>Conclusions</h4>Both 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. |
| first_indexed | 2024-12-22T12:53:45Z |
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| id | doaj.art-08c3eb873d4a481a87adb13d00e87518 |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-22T12:53:45Z |
| publishDate | 2016-01-01 |
| publisher | Public Library of Science (PLoS) |
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| spelling | doaj.art-08c3eb873d4a481a87adb13d00e875182022-12-21T18:25:10ZengPublic Library of Science (PLoS)PLoS ONE1932-62032016-01-01115e015510010.1371/journal.pone.0155100Relevance of Interleukin-6 and D-Dimer for Serious Non-AIDS Morbidity and Death among HIV-Positive Adults on Suppressive Antiretroviral Therapy.Birgit GrundJason V BakerSteven G DeeksJulian WolfsonDeborah WentworthAlessandro Cozzi-LepriCalvin J CohenAndrew PhillipsJens D LundgrenJames D NeatonINSIGHT SMART/ESPRIT/SILCAAT Study Group<h4>Background</h4>Despite 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.<h4>Methods</h4>In 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.<h4>Results</h4>Over 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.<h4>Conclusions</h4>Both 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.https://doi.org/10.1371/journal.pone.0155100 |
| spellingShingle | Birgit Grund Jason V Baker Steven G Deeks Julian Wolfson Deborah Wentworth Alessandro Cozzi-Lepri Calvin J Cohen Andrew Phillips Jens D Lundgren James D Neaton INSIGHT SMART/ESPRIT/SILCAAT Study Group Relevance of Interleukin-6 and D-Dimer for Serious Non-AIDS Morbidity and Death among HIV-Positive Adults on Suppressive Antiretroviral Therapy. PLoS ONE |
| title | Relevance of Interleukin-6 and D-Dimer for Serious Non-AIDS Morbidity and Death among HIV-Positive Adults on Suppressive Antiretroviral Therapy. |
| title_full | Relevance of Interleukin-6 and D-Dimer for Serious Non-AIDS Morbidity and Death among HIV-Positive Adults on Suppressive Antiretroviral Therapy. |
| title_fullStr | Relevance of Interleukin-6 and D-Dimer for Serious Non-AIDS Morbidity and Death among HIV-Positive Adults on Suppressive Antiretroviral Therapy. |
| title_full_unstemmed | Relevance of Interleukin-6 and D-Dimer for Serious Non-AIDS Morbidity and Death among HIV-Positive Adults on Suppressive Antiretroviral Therapy. |
| title_short | Relevance of Interleukin-6 and D-Dimer for Serious Non-AIDS Morbidity and Death among HIV-Positive Adults on Suppressive Antiretroviral Therapy. |
| title_sort | relevance of interleukin 6 and d dimer for serious non aids morbidity and death among hiv positive adults on suppressive antiretroviral therapy |
| url | https://doi.org/10.1371/journal.pone.0155100 |
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