Objective: The Simplification of antiretroviral therapy with Tenofovir-Emtricitabine or Abacavir-Lamivudine trial (STEAL) study randomized HIV participants to switch existing nucleoside reverse transcriptase inhibitors (NRTI) to either abacavir/lamivudine (ABC/3TC; n = 179) or tenofovir/emtricitabine (TDF/FTC; n = 178). An increased risk in cardiovascular disease (CVD) was reported (hazard ratio 7.7, P = 0.048) in ABC/3TC recipients compared with TDF/FTC in the STEAL study. The impact of ABC/3TC treatment on a range of CVD and inflammatory biomarkers was explored.
Design and methods: Biomarkers were assessed at 0, 12, 24, and 48 weeks to examine: inflammation - high sensitive C-reactive protein, amyloid-P, amyloid-A, interleukin 6, interleukin 10, interferon α, and macrophage migration inhibitory factor; coagulation - D-dimer and fibrinogen; platelet function - soluble P-selectin; endothelial function - vascular cell adhesion molecule 1 and intercellular adhesion molecule 1; renal function - cystatin C. The primary endpoint was the difference between arms for mean change from baseline to week 12. Secondary analyses were differences between groups for mean change from baseline to weeks 24 and 48, time-weighted change from baseline to week 48, and changes to week 12 stratified by Framingham CVD risk score at baseline.
Results: Sera were available from 330 (92%) of 357 participants. At baseline, all biomarkers were similar between treatment arms and when stratified for baseline NRTI exposure. There were no significant differences between treatment arms in the mean change from baseline to week 12 for any biomarkers. No consistent between-group differences were seen in the secondary analyses that could suggest one pathophysiological pathway.
Conclusion: A thorough examination of selected biomarkers associated with cardiovascular morbidity and mortality did not reveal associations with the use of ABC/3TC relative to use of TDF/FTC.