Pre-ART levels of inflammation and coagulation markers are strong predictors of death in a south african cohort with advanced HIV disease

Lotty Ledwaba, Jorge A. Tavel, Paul Khabo, Patrick Maja, Jing Qin, Phumele Sangweni, Xiao Liu, Dean Follmann, Julia A. Metcalf, Susan Orsega, Beth Baseler, James D. Neaton, H. Clifford Lane, Project Phidisa Biomarkers Team The Project Phidisa Biomarkers Team

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Abstract

Background: Levels of high-sensitivity C-reactive protein (hsCRP), interleukin-6 (IL-6), and D-dimer predict mortality in HIV patients on antiretroviral therapy (ART) with relatively preserved CD4+ T cell counts. We hypothesized that elevated pre-ART levels of these markers among patients with advanced HIV would be associated with an increased risk of death following the initiation of ART. Methods: Pre-ART plasma from patients with advanced HIV in South Africa was used to measure hsCRP, IL-6 and D-dimer. Using a nested case-control study design, the biomarkers were measured for 187 deaths and two controls matched on age, sex, clinical site, follow-up time and CD4+ cell counts. Odds ratios were estimated using conditional logistic regression. In addition, for a random sample of 100 patients, biomarkers were measured at baseline and 6 months following randomization to determine whether ART altered their levels. Results: Median baseline biomarkers levels for cases and controls, respectively, were 11.25 vs. 3.6 mg/L for hsCRP, 1.41 vs. 0.98 mg/L for D-dimer, and 9.02 vs. 4.20 pg/mL for IL-6 (all p<0.0001). Adjusted odds ratios for the highest versus lowest quartile of baseline biomarker levels were 3.5 (95% CI: 1.9-6.7) for hsCRP, 2.6 (95%CI 1.4-4.9) for D-dimer, and 3.8 (95% CI: 1.8-7.8) for IL-6. These associations were stronger for deaths that occurred more proximal to the biomarker measurements. Levels of D-dimer and IL-6, but not hsCRP, were significantly lower at month 6 after commencing ART compared to baseline (p<0.0001). Conclusions: Among patients with advanced HIV disease, elevated pre-ART levels of hsCRP, IL-6 and D-dimer are strongly associated with early mortality after commencing ART. Elevated levels of inflammatory and coagulation biomarkers may identify patients who may benefit from aggressive clinical monitoring after commencing ART. Further investigation of strategies to reduce biomarkers of inflammation and coagulation in patients with advanced HIV disease is warranted.

Original languageEnglish (US)
Article numbere24243
JournalPloS one
Volume7
Issue number3
DOIs
StatePublished - Mar 20 2012

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Biomarkers
Coagulation
coagulation
C-Reactive Protein
inflammation
C-reactive protein
Interleukin-6
HIV
death
Inflammation
biomarkers
interleukin-6
therapeutics
Therapeutics
CD4 Lymphocyte Count
odds ratio
T-cells
Odds Ratio
Mortality
fibrin fragment D

All Science Journal Classification (ASJC) codes

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)

Cite this

Ledwaba, L., Tavel, J. A., Khabo, P., Maja, P., Qin, J., Sangweni, P., ... The Project Phidisa Biomarkers Team, P. P. B. T. (2012). Pre-ART levels of inflammation and coagulation markers are strong predictors of death in a south african cohort with advanced HIV disease. PloS one, 7(3), [e24243]. https://doi.org/10.1371/journal.pone.0024243
Ledwaba, Lotty ; Tavel, Jorge A. ; Khabo, Paul ; Maja, Patrick ; Qin, Jing ; Sangweni, Phumele ; Liu, Xiao ; Follmann, Dean ; Metcalf, Julia A. ; Orsega, Susan ; Baseler, Beth ; Neaton, James D. ; Lane, H. Clifford ; The Project Phidisa Biomarkers Team, Project Phidisa Biomarkers Team. / Pre-ART levels of inflammation and coagulation markers are strong predictors of death in a south african cohort with advanced HIV disease. In: PloS one. 2012 ; Vol. 7, No. 3.
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title = "Pre-ART levels of inflammation and coagulation markers are strong predictors of death in a south african cohort with advanced HIV disease",
abstract = "Background: Levels of high-sensitivity C-reactive protein (hsCRP), interleukin-6 (IL-6), and D-dimer predict mortality in HIV patients on antiretroviral therapy (ART) with relatively preserved CD4+ T cell counts. We hypothesized that elevated pre-ART levels of these markers among patients with advanced HIV would be associated with an increased risk of death following the initiation of ART. Methods: Pre-ART plasma from patients with advanced HIV in South Africa was used to measure hsCRP, IL-6 and D-dimer. Using a nested case-control study design, the biomarkers were measured for 187 deaths and two controls matched on age, sex, clinical site, follow-up time and CD4+ cell counts. Odds ratios were estimated using conditional logistic regression. In addition, for a random sample of 100 patients, biomarkers were measured at baseline and 6 months following randomization to determine whether ART altered their levels. Results: Median baseline biomarkers levels for cases and controls, respectively, were 11.25 vs. 3.6 mg/L for hsCRP, 1.41 vs. 0.98 mg/L for D-dimer, and 9.02 vs. 4.20 pg/mL for IL-6 (all p<0.0001). Adjusted odds ratios for the highest versus lowest quartile of baseline biomarker levels were 3.5 (95{\%} CI: 1.9-6.7) for hsCRP, 2.6 (95{\%}CI 1.4-4.9) for D-dimer, and 3.8 (95{\%} CI: 1.8-7.8) for IL-6. These associations were stronger for deaths that occurred more proximal to the biomarker measurements. Levels of D-dimer and IL-6, but not hsCRP, were significantly lower at month 6 after commencing ART compared to baseline (p<0.0001). Conclusions: Among patients with advanced HIV disease, elevated pre-ART levels of hsCRP, IL-6 and D-dimer are strongly associated with early mortality after commencing ART. Elevated levels of inflammatory and coagulation biomarkers may identify patients who may benefit from aggressive clinical monitoring after commencing ART. Further investigation of strategies to reduce biomarkers of inflammation and coagulation in patients with advanced HIV disease is warranted.",
author = "Lotty Ledwaba and Tavel, {Jorge A.} and Paul Khabo and Patrick Maja and Jing Qin and Phumele Sangweni and Xiao Liu and Dean Follmann and Metcalf, {Julia A.} and Susan Orsega and Beth Baseler and Neaton, {James D.} and Lane, {H. Clifford} and {The Project Phidisa Biomarkers Team}, {Project Phidisa Biomarkers Team}",
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month = "3",
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issn = "1932-6203",
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Ledwaba, L, Tavel, JA, Khabo, P, Maja, P, Qin, J, Sangweni, P, Liu, X, Follmann, D, Metcalf, JA, Orsega, S, Baseler, B, Neaton, JD, Lane, HC & The Project Phidisa Biomarkers Team, PPBT 2012, 'Pre-ART levels of inflammation and coagulation markers are strong predictors of death in a south african cohort with advanced HIV disease', PloS one, vol. 7, no. 3, e24243. https://doi.org/10.1371/journal.pone.0024243

Pre-ART levels of inflammation and coagulation markers are strong predictors of death in a south african cohort with advanced HIV disease. / Ledwaba, Lotty; Tavel, Jorge A.; Khabo, Paul; Maja, Patrick; Qin, Jing; Sangweni, Phumele; Liu, Xiao; Follmann, Dean; Metcalf, Julia A.; Orsega, Susan; Baseler, Beth; Neaton, James D.; Lane, H. Clifford; The Project Phidisa Biomarkers Team, Project Phidisa Biomarkers Team.

In: PloS one, Vol. 7, No. 3, e24243, 20.03.2012.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Pre-ART levels of inflammation and coagulation markers are strong predictors of death in a south african cohort with advanced HIV disease

AU - Ledwaba, Lotty

AU - Tavel, Jorge A.

AU - Khabo, Paul

AU - Maja, Patrick

AU - Qin, Jing

AU - Sangweni, Phumele

AU - Liu, Xiao

AU - Follmann, Dean

AU - Metcalf, Julia A.

AU - Orsega, Susan

AU - Baseler, Beth

AU - Neaton, James D.

AU - Lane, H. Clifford

AU - The Project Phidisa Biomarkers Team, Project Phidisa Biomarkers Team

PY - 2012/3/20

Y1 - 2012/3/20

N2 - Background: Levels of high-sensitivity C-reactive protein (hsCRP), interleukin-6 (IL-6), and D-dimer predict mortality in HIV patients on antiretroviral therapy (ART) with relatively preserved CD4+ T cell counts. We hypothesized that elevated pre-ART levels of these markers among patients with advanced HIV would be associated with an increased risk of death following the initiation of ART. Methods: Pre-ART plasma from patients with advanced HIV in South Africa was used to measure hsCRP, IL-6 and D-dimer. Using a nested case-control study design, the biomarkers were measured for 187 deaths and two controls matched on age, sex, clinical site, follow-up time and CD4+ cell counts. Odds ratios were estimated using conditional logistic regression. In addition, for a random sample of 100 patients, biomarkers were measured at baseline and 6 months following randomization to determine whether ART altered their levels. Results: Median baseline biomarkers levels for cases and controls, respectively, were 11.25 vs. 3.6 mg/L for hsCRP, 1.41 vs. 0.98 mg/L for D-dimer, and 9.02 vs. 4.20 pg/mL for IL-6 (all p<0.0001). Adjusted odds ratios for the highest versus lowest quartile of baseline biomarker levels were 3.5 (95% CI: 1.9-6.7) for hsCRP, 2.6 (95%CI 1.4-4.9) for D-dimer, and 3.8 (95% CI: 1.8-7.8) for IL-6. These associations were stronger for deaths that occurred more proximal to the biomarker measurements. Levels of D-dimer and IL-6, but not hsCRP, were significantly lower at month 6 after commencing ART compared to baseline (p<0.0001). Conclusions: Among patients with advanced HIV disease, elevated pre-ART levels of hsCRP, IL-6 and D-dimer are strongly associated with early mortality after commencing ART. Elevated levels of inflammatory and coagulation biomarkers may identify patients who may benefit from aggressive clinical monitoring after commencing ART. Further investigation of strategies to reduce biomarkers of inflammation and coagulation in patients with advanced HIV disease is warranted.

AB - Background: Levels of high-sensitivity C-reactive protein (hsCRP), interleukin-6 (IL-6), and D-dimer predict mortality in HIV patients on antiretroviral therapy (ART) with relatively preserved CD4+ T cell counts. We hypothesized that elevated pre-ART levels of these markers among patients with advanced HIV would be associated with an increased risk of death following the initiation of ART. Methods: Pre-ART plasma from patients with advanced HIV in South Africa was used to measure hsCRP, IL-6 and D-dimer. Using a nested case-control study design, the biomarkers were measured for 187 deaths and two controls matched on age, sex, clinical site, follow-up time and CD4+ cell counts. Odds ratios were estimated using conditional logistic regression. In addition, for a random sample of 100 patients, biomarkers were measured at baseline and 6 months following randomization to determine whether ART altered their levels. Results: Median baseline biomarkers levels for cases and controls, respectively, were 11.25 vs. 3.6 mg/L for hsCRP, 1.41 vs. 0.98 mg/L for D-dimer, and 9.02 vs. 4.20 pg/mL for IL-6 (all p<0.0001). Adjusted odds ratios for the highest versus lowest quartile of baseline biomarker levels were 3.5 (95% CI: 1.9-6.7) for hsCRP, 2.6 (95%CI 1.4-4.9) for D-dimer, and 3.8 (95% CI: 1.8-7.8) for IL-6. These associations were stronger for deaths that occurred more proximal to the biomarker measurements. Levels of D-dimer and IL-6, but not hsCRP, were significantly lower at month 6 after commencing ART compared to baseline (p<0.0001). Conclusions: Among patients with advanced HIV disease, elevated pre-ART levels of hsCRP, IL-6 and D-dimer are strongly associated with early mortality after commencing ART. Elevated levels of inflammatory and coagulation biomarkers may identify patients who may benefit from aggressive clinical monitoring after commencing ART. Further investigation of strategies to reduce biomarkers of inflammation and coagulation in patients with advanced HIV disease is warranted.

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U2 - 10.1371/journal.pone.0024243

DO - 10.1371/journal.pone.0024243

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JO - PLoS One

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ER -