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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
medicine
The kynurenine pathway of tryptophan catabolism, CD4
+
T-cell recovery, and mortality among HIV-infected Ugandans initiating antiretroviral therapy
Journal of Infectious Diseases, Volume 210, No. 3, Year 2014
Notification
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Description
Background. Human immunodeficiency virus (HIV) infection-induced indoleamine 2,3-dioxygenase-1 (IDO) expression in activated monocytes and dendritic cells catabolizes tryptophan to kynurenine and other downstream catabolites that inhibit T-cell proliferation and interleukin 17 (IL-17) production. The prognostic significance of this pathway in treated HIV disease is unknown. Methods. We measured systemic IDO activity (calculated as the ratio of plasma levels of kynurenine to tryptophan; hereafter, the "KT ratio") in HIV-infected Ugandans before and during antiretroviral therapy (ART)-mediated viral suppression and its association with the rate of subsequent CD4+ T-cell count recovery and mortality. Results. Among 435 participants, a higher pre-ART KT ratio was associated with a higher plasma virus load (P < .001) and lipopolysaccharide level (P = .018), a lower CD4+ T-cell count (P < .001), and female sex (P = .047). Through month 12 of ART-mediated viral suppression, the plasma KT ratio decreased by approximately 50% (P < .001). After adjustment for pre-ART CD4+ T-cell count, virus load, age, and sex, a higher month 12 KT ratio predicted a slower rate of subsequent CD4+ T-cell count recovery (P = .001). Thirty-nine participants died. After adjustment for pre-ART CD4+ T-cell count, virus load, body mass index, sex, and age, a higher pre-ART and month 6 KT ratio predicted increased mortality (P ≤ .016). Conclusions. The kynurenine pathway of tryptophan catabolism independently predicts poor CD4 + T-cell count recovery and increased mortality among HIV-infected Ugandans initiating ART and may be an important target for interventions. © The Author 2014.
Authors & Co-Authors
Byakwaga, Helen
United States, San Francisco
University of California, San Francisco
Uganda, Mbarara
Mbarara University of Science and Technology
Boum, Yap I.
Uganda, Mbarara
Mbarara University of Science and Technology
France, Paris
Epicentre
Huang, Yong
United States, San Francisco
University of California, San Francisco
Muzoora, Conrad K.
Uganda, Mbarara
Mbarara University of Science and Technology
Kembabazi, Annet
Uganda, Mbarara
Mbarara University of Science and Technology
Weiser, Sheri D.
United States, San Francisco
Ucsf School of Medicine
Bennett, John E.
United States, San Francisco
University of California, San Francisco
Cao, Huyen L.
United States, Sacramento
California Department of Health Services
Haberer, Jessica Elizabeth
United States, Boston
Harvard Medical School
United States, Boston
Massachusetts General Hospital
Deeks, Steven G.
United States, San Francisco
Ucsf School of Medicine
Bangsberg, David R.
United States, Boston
Massachusetts General Hospital
United States, Boston
Harvard T.h. Chan School of Public Health
United States, Harvard
Mit and Harvard
McCune, Joseph M.
United States, San Francisco
Ucsf School of Medicine
Martin, Jeffrey N.
United States, San Francisco
University of California, San Francisco
Hunt, Peter W.
United States, San Francisco
Ucsf School of Medicine
Statistics
Citations: 107
Authors: 14
Affiliations: 9
Identifiers
Doi:
10.1093/infdis/jiu115
ISSN:
00221899
e-ISSN:
15376613
Research Areas
Infectious Diseases
Participants Gender
Female