Does an Index Composed of Clinical Data Reflect Effects of Inflammation, Coagulation, and Monocyte Activation on Mortality Among Those Aging With HIV?

• Published in: Clinical infectious diseases Vol. 54; no. 7; pp. 984 - 994
• Main Authors: Justice, Amy C., Freiberg, Matthew S., Tracy, Russ, Kuller, Lew, Tate, Janet P., Goetz, Matthew Bidwell, Fiellin, David A., Vanasse, Gary J., Butt, Adeel A., Rodriguez-Barradas, Maria C., Gibert, Cynthia, Oursler, Kris Ann, Deeks, Steven G., Bryant, Kendall
• Format: Journal Article
• Language: English
• Published: Oxford Oxford University Press 01.04.2012
• Subjects: Adult; Aged; Aged, 80 and over; Aging; Antiretrovirals; Biological and medical sciences; Biological markers; Biomarkers; Biomarkers - blood; Coagulation; Cohort studies; Female; Fibrin Fibrinogen Degradation Products - analysis; Hemoglobin; Hepatitis C virus; HIV; HIV 1; HIV infections; HIV Infections - diagnosis; HIV Infections - mortality; HIV Infections - pathology; HIV-1 - immunology; HIV-1 - pathogenicity; HIV/AIDS; Human immunodeficiency virus; Human immunodeficiency virus 1; Human viral diseases; Humans; Immunodeficiencies; Immunodeficiencies. Immunoglobulinopathies; Immunopathology; Infections; Infectious diseases; Inflammation; Interleukin-6 - blood; Lipopolysaccharide Receptors - blood; Male; Medical sciences; Middle Aged; Mortality; Prognosis; Ribonucleic acid; RNA; Survival Analysis; Viral diseases; Viral diseases of the lymphoid tissue and the blood. Aids; Immunopathology; Prognosis; Monocyte; Mortality; Coagulation; Retroviridae; AIDS; Inflammation; Immune deficiency; Lentivirus; Infection; Virus; Viral disease; Human immunodeficiency virus
• ISSN: 1058-4838; 1537-6591; 1537-6591
• DOI: 10.1093/cid/cir989

Background. When added to age, CD4 count and human immunodeficiency virus type 1 (HIV-1) RNA alone (Restricted Index), hemoglobin, FIB-4 Index, hepatitis C virus (HCV), and estimated glomerular filtration rate improve prediction of mortality. Weighted and combined, these 7 routine clinical variables constitute the Veterans Aging Cohort Study (VACS) Index. Because nonroutine biomarkers of inflammation (interleukin 6 [IL-6]), coagulation (D-dimer), and monocyte activation (sCD14) also predict mortality, we test the association of these indices and biomarkers with each other and with mortality. Methods. Samples from 1302 HIV-infected veterans on antiretroviral therapy were analyzed. Indices were calculated closest to date of collection. We calculated Spearman correlations stratified by HIV-1 RNA and HCV status and measured association with mortality using C statistics and net reclassification improvement (NRI). Results. Of 1302 subjects, 915 had HIV-1 RNA <500 copies/mL and 154 died. The VACS Index was more correlated with IL-6, D-dimer, and sCD14 than the Restricted Index (P < .001). It was also more predictive of mortality (C statistic, 0.76; 95% confidence interval [CI], .72-.80) than any biomarker (C statistic, 0.66-0.70) or the Restricted Index (C statistic, 0.71; 95% CI, .67-.75). Compared to the Restricted Index alone, NRI resulted from incremental addition of VACS Index components (10%), D-dimer (7%), and sCD14 (4%), but not from IL-6 (0%). Conclusions. Among HIV-infected individuals, independent of CD4, HIV-1 RNA, and age, hemoglobin and markers of liver and renal injury are associated with inflammation. Addition of D-dimer and sCD14, but not IL-6, improves the predictive accuracy of the VACS Index for mortality.