Longitudinal comparison of inflammatory, coagulation and metabolic biomarkers in patients who start ART versus patients who remain ART‐naïve

In: Journal of the International AIDS Society, Band 15, Heft S4, S. 1-1

Abstract

There are very limited data on the impact of ART initiation on inflammatory and coagulation biomarkers compared to patients who remain ART naïve [1]. We designed a prospective comparative study to evaluate these changes. Prospective observational cohort study of HIV‐infected patients who start ART and a group of age‐matched controls who remain ART‐naïve. Blood levels of insulin, fibrinogen, D‐dimer, high‐sensitivity PCR, inflammatory (IL‐1β, IL‐6, MCP‐1 and sCD40) and anti‐inflammatory cytokines (IL‐4), were compared at baseline, 24 weeks and 48 weeks. Summary of results: 94 patients included (57 treated, 37 controls). Baseline characteristics were balanced except for (treated/controls): median [IQR], HIV duration (0.9 [0.4–2.4] / 2.7 [0.6–5.5]) years, CD4 nadir (262 [198–317] / 452 [367–553]) cells/µl, viral load (4.4 [4–5.1] / 3.8 [3.1–4.4]) log cop/ml, current CD4 count (283 [213–323] / 525 [449–669]) cells/µl, HDL cholesterol (38 [29–45] / 41 [36–50]) mg/dl and female gender (8.8%/35%). There were no differences between groups in baseline biomarkers levels except that those starting ART had lower median [IQR] IL‐1β (4.1 [3.5–4.7] vs. 4.6 [3.7–6.8] pg/ml; p= 0.019) and lower IL–6 levels (4 [3.4–4.6] vs. 5.2 [4.2–6.6] pg/ml; p< 0.001). No significant correlation was found between biomarkers and baseline viral load. 91% of treated patients achieved viral suppression (<50 c/ml). There were statistically significant differences between groups at week 48 with lower (mean [95% CI]) D‐dimer (−138.2 [−268.0, −8.4] mg/L; p=0.001), IL‐1β (−0.6 [−0.9, −0.4] pg/ml; p<0.001) and higher IL‐4 (0.6 [0.2, 0.9] pg/ml; p=0.004) in those starting ART. In the ART‐naïve group there were significant increases of IL‐1β (1.3 [0.9, 1.6] pg/ml; p<0.001), sCD40 (22.7 [0.8, 44.6] AU; p=0.043), IL‐6 (0.5 [0.0, 0.9] pg/ml; p= 0.049) and a significant decrease of IL‐4 (−0.7 [−1.1, −0.3] pg/ml; p=0.001) levels. After 48 weeks of ART there were statistically significant decreases in pro‐inflammatory and coagulation markers (Figure 1) while levels of anti‐inflammatory cytokines (e.g. IL‐4) were significantly increased. Opposite trends were found in controls.In conclusion, compared to untreated controls, 48 weeks of effective ART significantly reduces pro‐inflammatory (IL‐1β, IL‐6), coagulation (fibrinogen, D‐dimer), and metabolic (insulin) markers and increases levels of an anti‐inflammatory cytokines like IL‐4.Median percentage changes in bio markers from baseline to week 48.image