Evaluation of adhesion molecules and immune parameters in HIV-infected patients treated with an atazanavir/ritonavir- compared with a lopinavir/ritonavir-based regimen

Abstract

Objectives: To evaluate changes in pro-atherosclerotic biomarkers and endothelial function in patients initiating two different PI-based regimens as part of ART.

Design: Prospective randomized 24 week study. Treatment-naive HIV-infected patients with CD4+ T cell count >250 cells/mm3 started PI-based regimens including atazanavir/ritonavir (Group A) or lopinavir/ritonavir (Group B) and were followed up in an observational follow-up study until week 96.

Methods: The expression of immune activation and adhesion molecules on CD4+ and CD8+ cells and plasma cytokine levels were assessed at weeks 0, 4, 12, 24, 48, 72 and 96. Flow-mediated dilation (FMD), pulse-wave velocity (PWV) and intima-media thickness (IMT) were measured at weeks 0 and 24. Median changes within (signed rank test) and between (Wilcoxon test) arms were calculated.

Results: Twenty-seven patients were enrolled, of whom 15 were treated with atazanavir/ritonavir and 12 with lopinavir/ritonavir. After 96 weeks of ART, CD25+/CD8+ T cells and plasma concentration of MCP-1/CCL-2 rose whereas CD44+/CD8+ T cells decreased significantly in both groups. Differences between treatments were noted for HLA-DRII+/CD8+, CD44+/CD4+ and CD11a+/CD4+, with significant increases in Group B versus Group A. No differences between groups regarding IMT, PWV and FMD were found at baseline and week 24.

Conclusions: ART initiation with PI-based regimens led to a decrease in pro-atherosclerotic biomarkers at week 24, which then rebounded at week 96. Lopinavir/ritonavir treatment resulted in an unfavourable modulation of such markers compared with atazanavir/ritonavir treatment.