Immunologic Pathways That Predict Mortality in HIV-Infected Ugandans Initiating Antiretroviral Therapy.
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.
University of California, San Francisco, USA
Sulggi
S
Lee
Mbarara University of Science and Technology, Uganda.
Helen
H
Byakwaga
Mbarara University of Science and Technology, Uganda.
Yap
Y
Boum
Temple University, Philadelphia, Pennsylvania.
Tricia H
TH
Burdo
Boston College, Massachusetts, USA
Kenneth C
KC
Williams
Case Western Reserve University, Cleveland, Ohio.
Michael M
MM
Lederman
University of California, San Francisco, USA
Yong
Y
Huang
University of Vermont, Burlington, USA
Russell P
RP
Tracy
California Department of Public Health, Richmond, USA
Huyen
H
Cao
Massachusetts General Hospital, Massachusetts|Harvard Medical School, Boston, Massachusetts.
Jessica E
JE
Haberer
Mbarara University of Science and Technology, Uganda.
Annet
A
Kembabazi
Health and Sciences University, Portland State University of Public Health, Portland, Oregon
David R
DR
Bangsberg
University of California, San Francisco, USA
Jeffrey N
JN
Martin
University of California, San Francisco, USA
Peter W
PW
Hunt
D000328:Adult; D019380:Anti-HIV Agents / Q000627:therapeutic use*; D015415:Biomarkers / Q000097:blood; D015331:Cohort Studies; D005260:Female; D005338:Fibrin Fibrinogen Degradation Products / Q000032:analysis; D015658:HIV Infections / Q000188:drug therapy* / Q000401:mortality*; D006801:Humans; D015850:Interleukin-6 / Q000097:blood; D007737:Kynurenine / Q000097:blood*; D018950:Lipopolysaccharide Receptors / Q000097:blood; D008297:Male; D015999:Multivariate Analysis; D011379:Prognosis; D016016:Proportional Hazards Models; D013601:T-Lymphocytes / Q000276:immunology; D014364:Tryptophan / Q000097:blood*; D014454:Uganda / Q000453:epidemiology; D019562:Viral Load
D019380:Anti-HIV Agents; D015415:Biomarkers; D005338:Fibrin Fibrinogen Degradation Products; C508600:IL6 protein, human; D015850:Interleukin-6; D018950:Lipopolysaccharide Receptors; C036309:fibrin fragment D; D007737:Kynurenine; D014364:Tryptophan
Africa.; D-dimer; HIV; IL-6; antiretroviral therapy; kynurenine; mortality; sCD14; tryptophan