Association of Soluble CD14 and Inflammatory Biomarkers With HIV-2 Disease Progression

Abstract

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. 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. 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). 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.