Pre-ART levels of inflammation and coagulation markers are strong predictors of death in a South African cohort with advanced HIV disease.
<h4>Background</h4>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...
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Public Library of Science (PLoS)
2012-01-01
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| Series: | PLoS ONE |
| Online Access: | https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0024243&type=printable |
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| author | 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 |
| author_facet | 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 |
| author_sort | Lotty Ledwaba |
| collection | DOAJ |
| description | <h4>Background</h4>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.<h4>Methods</h4>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.<h4>Results</h4>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).<h4>Conclusions</h4>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.<h4>Trial registration</h4>Parent study: ClinicalTrials.gov NCT00342355. |
| format | Article |
| id | doaj-art-d76bfe5f54774b2fb1bbe9b0fb548079 |
| institution | DOAJ |
| issn | 1932-6203 |
| language | English |
| publishDate | 2012-01-01 |
| publisher | Public Library of Science (PLoS) |
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| spelling | doaj-art-d76bfe5f54774b2fb1bbe9b0fb5480792025-08-20T03:09:48ZengPublic Library of Science (PLoS)PLoS ONE1932-62032012-01-0173e2424310.1371/journal.pone.0024243Pre-ART levels of inflammation and coagulation markers are strong predictors of death in a South African cohort with advanced HIV disease.Lotty LedwabaJorge A TavelPaul KhaboPatrick MajaJing QinPhumele SangweniXiao LiuDean FollmannJulia A MetcalfSusan OrsegaBeth BaselerJames D NeatonH Clifford LaneProject Phidisa Biomarkers Team<h4>Background</h4>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.<h4>Methods</h4>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.<h4>Results</h4>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).<h4>Conclusions</h4>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.<h4>Trial registration</h4>Parent study: ClinicalTrials.gov NCT00342355.https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0024243&type=printable |
| spellingShingle | 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 Pre-ART levels of inflammation and coagulation markers are strong predictors of death in a South African cohort with advanced HIV disease. PLoS ONE |
| title | Pre-ART levels of inflammation and coagulation markers are strong predictors of death in a South African cohort with advanced HIV disease. |
| title_full | Pre-ART levels of inflammation and coagulation markers are strong predictors of death in a South African cohort with advanced HIV disease. |
| title_fullStr | Pre-ART levels of inflammation and coagulation markers are strong predictors of death in a South African cohort with advanced HIV disease. |
| title_full_unstemmed | Pre-ART levels of inflammation and coagulation markers are strong predictors of death in a South African cohort with advanced HIV disease. |
| title_short | Pre-ART levels of inflammation and coagulation markers are strong predictors of death in a South African cohort with advanced HIV disease. |
| title_sort | pre art levels of inflammation and coagulation markers are strong predictors of death in a south african cohort with advanced hiv disease |
| url | https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0024243&type=printable |
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