d-Dimer and CRP levels are elevated prior to antiretroviral treatment in patients who develop IRIS

Abstract

Biomarkers could be useful in evaluating immune reconstitution inflammatory syndrome (IRIS). A cohort of 45 HIV-1-infected, antiretroviral treatment (ART)-naive patients with baseline CD4 T cell counts <or=100 cells/microL who were started on ART, suppressed HIV-RNA to <50 copies/mL, and seen every 1-3 months for 1 year were retrospectively evaluated for suspected or confirmed IRIS. d-Dimer, C-reactive protein (CRP), and selected autoantibodies were analyzed at baseline, 1 and 3 months post-ART in cryopreserved plasma. Median differences between cases and controls were compared with Mann-Whitney and Fisher's exact tests. Sixteen patients (35.6%) developed IRIS (median of 35 days post-ART initiation): unmasking=8, paradoxical=7, autoimmune=1. Pre-ART d-dimer and CRP were higher in IRIS cases versus controls (d-dimer: 0.89 mg/L versus 0.66 mg /L, p=0.037; CRP: 0.74 mg/L versus 0.39 mg/L, p=0.022), while d-dimer was higher in unmasking cases at IRIS onset (2.04 mg/L versus 0.36 mg /L, p=0.05). These biomarkers may be useful in identifying patients at risk for IRIS.

Figure 1. Baseline plasma inflammatory marker levels in IRIS cases versus non-IRIS controls

Median values and interquartile ranges are shown for A) D-dimer and B) C-reactive protein in non-IRIS controls (closed circles) versus confirmed (closed squares) plus suspected (open squares) IRIS cases. Intergroup comparisons were done with the Mann-Whitney U test.

Figure 2. Longitudinal changes in plasma inflammatory markers among confirmed plus suspected IRIS cases versus non-IRIS controls

Median values are shown at baseline (BL), Month 1 (M1), and Month 3 (M3) for D-dimer (A and C) and C-reactive protein (B and D) in non-IRIS controls (closed circles and dashed line) versus confirmed plus suspected total IRIS cases (open circles and solid line) in Panels A and B or unmasking IRIS cases (open red squares and solid red line) and paradoxical IRIS cases (open blue diamonds and solid blue line) in Panels C and D. Intergroup comparisons versus non-IRIS controls were done with the Mann-Whitney U test. *p < 0.05

Figure 3. D-dimer at Month 1 among confirmed unmasking and paradoxical IRIS cases versus non-IRIS controls

Median values and interquartile ranges are shown for non-IRIS control (closed circles), unmasking IRIS (open squares), and paradoxical IRIS (open diamonds) cases at Month 1 (M1). Intergroup comparisons versus non-IRIS controls were done with the Mann-Whitney U test.