Immunologic pathways that predict mortality in HIV-infected Ugandans initiating antiretroviral therapy

Sulggi Lee; Helen Byakwaga; Yap Boum; Tricia H. Burdo; Kenneth C. Williams; Michael M. Lederman; Yong Huang; Russell P. Tracy; Huyen Cao; Jessica E. Haberer; Annet Kembabazi; David R. Bangsberg; Jeffrey N. Martin; Peter W. Hunt

doi:10.1093/infdis/jix113

Immunologic pathways that predict mortality in HIV-infected Ugandans initiating antiretroviral therapy

Sulggi Lee, Helen Byakwaga, Yap Boum, Tricia H. Burdo, Kenneth C. Williams, Michael M. Lederman, Yong Huang, Russell P. Tracy, Huyen Cao, Jessica E. Haberer, Annet Kembabazi, David R. Bangsberg, Jeffrey N. Martin, Peter W. Hunt

School Of Public Health

Research output: Contribution to journal › Article › peer-review

29 Scopus citations

Abstract

The plasma kynurenine/tryptophan (KT) ratio, a marker of adaptive immune defects, strongly predicts mortality during treated human immunodeficiency virus (HIV) disease in Ugandans as compared to US-based populations. Here, the KT ratio and T-cell and plasma biomarkers of immune activation were measured among 535 HIV-infected Ugandans prior to ART initiation and at month 6 of viral suppression. The month 6 KT ratio (adjusted hazard ratio [aHR], 2.74), soluble CD14 level (aHR, 2.32), interleukin 6 level (aHR, 2.34), and D-dimer level (aHR, 1.95) were associated with mortality occurring ≥6 months after ART initiation. The KT ratio remained significantly predictive of mortality even after adjustment for the additional biomarkers, suggesting an independent contribution to clinical outcomes in resource-limited settings.

Original language	English (US)
Pages (from-to)	1270-1274
Number of pages	5
Journal	Journal of Infectious Diseases
Volume	215
Issue number	8
DOIs	https://doi.org/10.1093/infdis/jix113
State	Published - Apr 15 2017

Keywords

Africa
Antiretroviral therapy
D-dimer
HIV
IL-6
Kynurenine
Mortality
Tryptophan
sCD14

ASJC Scopus subject areas

Immunology and Allergy
Infectious Diseases

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10.1093/infdis/jix113

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Lee, S., Byakwaga, H., Boum, Y., Burdo, T. H., Williams, K. C., Lederman, M. M., Huang, Y., Tracy, R. P., Cao, H., Haberer, J. E., Kembabazi, A., Bangsberg, D. R., Martin, J. N., & Hunt, P. W. (2017). Immunologic pathways that predict mortality in HIV-infected Ugandans initiating antiretroviral therapy. Journal of Infectious Diseases, 215(8), 1270-1274. https://doi.org/10.1093/infdis/jix113

Lee, S, Byakwaga, H, Boum, Y, Burdo, TH, Williams, KC, Lederman, MM, Huang, Y, Tracy, RP, Cao, H, Haberer, JE, Kembabazi, A, Bangsberg, DR, Martin, JN & Hunt, PW 2017, 'Immunologic pathways that predict mortality in HIV-infected Ugandans initiating antiretroviral therapy', Journal of Infectious Diseases, vol. 215, no. 8, pp. 1270-1274. https://doi.org/10.1093/infdis/jix113

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title = "Immunologic pathways that predict mortality in HIV-infected Ugandans initiating antiretroviral therapy",

abstract = "The plasma kynurenine/tryptophan (KT) ratio, a marker of adaptive immune defects, strongly predicts mortality during treated human immunodeficiency virus (HIV) disease in Ugandans as compared to US-based populations. Here, the KT ratio and T-cell and plasma biomarkers of immune activation were measured among 535 HIV-infected Ugandans prior to ART initiation and at month 6 of viral suppression. The month 6 KT ratio (adjusted hazard ratio [aHR], 2.74), soluble CD14 level (aHR, 2.32), interleukin 6 level (aHR, 2.34), and D-dimer level (aHR, 1.95) were associated with mortality occurring ≥6 months after ART initiation. The KT ratio remained significantly predictive of mortality even after adjustment for the additional biomarkers, suggesting an independent contribution to clinical outcomes in resource-limited settings.",

keywords = "Africa, Antiretroviral therapy, D-dimer, HIV, IL-6, Kynurenine, Mortality, Tryptophan, sCD14",

author = "Sulggi Lee and Helen Byakwaga and Yap Boum and Burdo, {Tricia H.} and Williams, {Kenneth C.} and Lederman, {Michael M.} and Yong Huang and Tracy, {Russell P.} and Huyen Cao and Haberer, {Jessica E.} and Annet Kembabazi and Bangsberg, {David R.} and Martin, {Jeffrey N.} and Hunt, {Peter W.}",

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AU - Lederman, Michael M.

AU - Huang, Yong

AU - Tracy, Russell P.

AU - Cao, Huyen

AU - Haberer, Jessica E.

AU - Kembabazi, Annet

AU - Bangsberg, David R.

AU - Martin, Jeffrey N.

AU - Hunt, Peter W.

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AB - The plasma kynurenine/tryptophan (KT) ratio, a marker of adaptive immune defects, strongly predicts mortality during treated human immunodeficiency virus (HIV) disease in Ugandans as compared to US-based populations. Here, the KT ratio and T-cell and plasma biomarkers of immune activation were measured among 535 HIV-infected Ugandans prior to ART initiation and at month 6 of viral suppression. The month 6 KT ratio (adjusted hazard ratio [aHR], 2.74), soluble CD14 level (aHR, 2.32), interleukin 6 level (aHR, 2.34), and D-dimer level (aHR, 1.95) were associated with mortality occurring ≥6 months after ART initiation. The KT ratio remained significantly predictive of mortality even after adjustment for the additional biomarkers, suggesting an independent contribution to clinical outcomes in resource-limited settings.

KW - Africa

KW - Antiretroviral therapy

KW - D-dimer

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KW - sCD14

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Immunologic pathways that predict mortality in HIV-infected Ugandans initiating antiretroviral therapy

Abstract

Keywords

ASJC Scopus subject areas

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