Association of soluble CD14 and inflammatory biomarkers with HIV-2 disease progression.
BACKGROUND
Human immunodeficiency virus type 2 (HIV-2) infection is characterized by a slower progression than HIV type 1. It is not known whether markers of inflammation such as high-sensitivity C-reactive protein (hsCRP), interleukin 6 (IL-6), and soluble CD14 (sCD14) may predict disease progression among HIV-2 patients.


METHODS
We performed longitudinal retrospective analysis using 384 samples from 71 patients included in the HIV-2 French cohort ANRS CO5 and followed for a median of 8 years. Baseline was the time of the first available measurement. Disease progression was defined by the occurrence of death, Centers for Disease Control and Prevention B/C stage HIV-related event, drop in CD4 <350 cells/µL, and HIV-2 RNA detection. Cox regression models and mixed models were used for statistical analyses.


RESULTS
At baseline, 75% of patients were asymptomatic, 34% were treated; 30% had detectable HIV-2 RNA load, and median CD4 cell count was 415/µL. The 3 biomarkers were positively related to each other. In adjusted analyses, sCD14 was the main factor explaining variation of hsCRP and IL-6 (P < .001). Lower CD4, older age, and advanced clinical stage were associated with higher sCD14. The biomarkers were correlated with HIV-2 RNA in unadjusted analyses only. Patients with baseline levels above either the median values (hsCRP = 1.38 mg/L; IL-6 = 1.97 pg/mL) or the highest quartile (sCD14 = 1.74 µg/mL) had a higher risk of disease progression (all P < .003). After adjustment for CD4 count, only sCD14 remained significantly associated with disease progression (hazard ratio, 3.59; P = .004).


CONCLUSIONS
In this cohort of HIV-2-infected patients, sCD14 represents a better predictive biomarker of disease progression than hsCRP or IL-6, independent of CD4.
Institut National de la Santé et de la Recherche Médicale (INSERM), Institut de Santé Publique, d'Epidémiologie et de Développement (ISPED), Centre INSERM U897-Epidemiologie-Biostatistique, Paris, France. rodolphe.thiebaut@isped.u-bordeaux2.fr
Rodolphe
R
Thiébaut
Charlotte
C
Charpentier
Florence
F
Damond
Audrey
A
Taieb
Romain
R
Antoine
Jacqueline
J
Capeau
Geneviève
G
Chêne
Gilles
G
Collin
Sophie
S
Matheron
Diane
D
Descamps
Françoise
F
Brun-Vézinet
D000328:Adult; D015415:Biomarkers / Q000097:blood; D002097:C-Reactive Protein / Q000378:metabolism; D015704:CD4 Antigens / Q000097:blood; D018450:Disease Progression; D005260:Female; D015658:HIV Infections / Q000097:blood / Q000276:immunology* / Q000821:virology; D015498:HIV-2 / Q000276:immunology / Q000302:isolation & purification*; D006801:Humans; D015850:Interleukin-6 / Q000097:blood; D053208:Kaplan-Meier Estimate; D018950:Lipopolysaccharide Receptors / Q000097:blood*; D008137:Longitudinal Studies; D008297:Male; D012189:Retrospective Studies; D019562:Viral Load
D015415:Biomarkers; D015704:CD4 Antigens; C508600:IL6 protein, human; D015850:Interleukin-6; D018950:Lipopolysaccharide Receptors; D002097:C-Reactive Protein