Early changes in inflammatory and pro-thrombotic biomarkers in patients initiating antiretroviral therapy with abacavir or tenofovir

Abstract

Background: Abacavir has been associated with an increased risk of acute myocardial infarction, but the pathogenic mechanisms remain unknown. We evaluated longitudinal changes in pro-atherosclerotic biomarkers in patients initiating abacavir or tenofovir.

Methods: Consecutive patients initiating antiretroviral therapy (ART) with abacavir/lamivudine or tenofovir/emtricitabine were included. Plasma levels of high sensitivity C reactive protein (hsCRP), interleukin-6 (IL-6), intercellular adhesion molecule-1, vascular cell adhesion molecule-1 (sVCAM-1) and plasminogen activator inhibitor-1 (PAI-1) were measured at baseline and at different time points throughout 48 weeks. Comparisons were adjusted for age, sex, ART status at inclusion, viral load, lipodystrophy, Framingham score and hepatitis C virus co-infection status.

Results: 50 patients were analyzed, 28 initiating abacavir and 22 tenofovir. The endothelial biomarker sVCAM-1 declined significantly in both treatment groups. hsCRP tended to increase soon after starting therapy with abacavir, a trend that was not seen in those initiating tenofovir. IL-6 significantly increased only at week 24 from baseline in patients on abacavir (+225%, p < 0.01) although the differences were not significant between groups. The procoagulant biomarker PAI-1 plasma levels increased from baseline at week 12 (+57%; p = 0.017), week 24 (+72%; p = 0.008), and week 48 (+149%; p < 0.001) in patients on tenofovir, but differences between groups were not statistically significant.

Conclusion: Changes in biomarkers of inflammation, coagulation, and endothelial function are not different in viremic patients starting ART with abacavir/lamivudine or tenofovir/emtricitabine. These changes occur in the early phases of treatment and include anti- and pro-atherosclerotic effects with both drugs.

Figure 1

Longitudinal evaluation of the percentage of change of different biomarkers from baseline by treatment groups. Percent of change from baseline calculated as 100 · [e^{mean difference from baseline} -1] in which mean difference from baseline is calculated on the natural log scale. P-value within arms reflecting whether the percent change from baseline is significantly different from 0: *P < 0.05, †P < 0.01, ‡P < 0.001. P-value derived from the comparison in percent change from baseline between the two treatment arms (abacavir vs. tenofovir): §P = 0.032. Comparisons were adjusted for age, sex, ART status at inclusion, viral load at baseline, lipodystrophy, Framingham score and hepatitis C virus co-infection status.