Immunologic Pathways That Predict Mortality in HIV-Infected Ugandans Initiating Antiretroviral Therapy. (1st March 2017)

• Record Type: Journal Article
• Authors: Lee, Sulggi; Byakwaga, Helen; Boum, Yap; Burdo, Tricia H.; Williams, Kenneth C.; Lederman, Michael M.; Huang, Yong; Tracy, Russell P.; Cao, Huyen; Haberer, Jessica E.; Kembabazi, Annet; Bangsberg, David R.; Martin, Jeffrey N.; Hunt, Peter W.
• Is Part Of: Journal of infectious diseases. Volume 215:Number 8(2017:Apr. 15)
• Page Start: 1270
• Page End: 1274
• Publication Date: 2017-03-01
• Subjects: HIV -- kynurenine -- tryptophan -- D-dimer -- IL-6 -- sCD14 -- mortality -- antiretroviral therapy -- Africa.; Communicable diseases -- Periodicals; Diseases -- Causes and theories of causation -- Periodicals; Medicine -- Periodicals; Communicable Diseases -- Periodicals; Electronic journals; 616.9
• DOI: 10.1093/infdis/jix113
• Languages: English
• ISSNs: 0022-1899

Abstract

Summary: The plasma kynurenine/tryptophan ratio, a marker of adaptive immune defects, remained significantly predictive of mortality, even after adjustment for other T-cell and plasma biomarkers, in human immunodeficiency virus (HIV)–infected Ugandans initiating antiretroviral therapy, suggesting an independent effect on mortality. 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.