Infectious Diseases Clinic, Azienda Socio Sanitaria Territoriale di Monza, San Gerardo Hospital-University of Milano-Bicocca, Monza, Italy.
Department of Biomedical and Clinical Sciences, University of Milano, Milan, Italy.
J Antimicrob Chemother. 2018 Aug 1;73(8):2162-2170. doi: 10.1093/jac/dky178.
To evaluate changes in pro-atherosclerotic biomarkers and endothelial function in patients initiating two different PI-based regimens as part of ART.
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.
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.
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.
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.
评估在开始两种不同基于蛋白酶抑制剂(PI)的治疗方案(作为 ART 的一部分)的患者中,促动脉粥样硬化生物标志物和内皮功能的变化。
前瞻性随机 24 周研究。CD4+T 细胞计数>250 个/毫米 3 的初治 HIV 感染患者开始接受基于 PI 的方案,包括阿扎那韦/利托那韦(A 组)或洛匹那韦/利托那韦(B 组),并在观察性随访研究中随访至第 96 周。
在第 0、4、12、24、48、72 和 96 周时评估 CD4+和 CD8+细胞上免疫激活和黏附分子的表达以及血浆细胞因子水平。在第 0 和 24 周时测量血流介导的扩张(FMD)、脉搏波速度(PWV)和内膜中层厚度(IMT)。计算臂内(符号秩检验)和臂间(Wilcoxon 检验)的中位数变化。
共纳入 27 例患者,其中 15 例接受阿扎那韦/利托那韦治疗,12 例接受洛匹那韦/利托那韦治疗。在接受 ART96 周后,两组患者的 CD25+/CD8+T 细胞和血浆 MCP-1/CCL-2 浓度均显著升高,而 CD44+/CD8+T 细胞则显著降低。两组之间的治疗差异在于 HLA-DRII+/CD8+、CD44+/CD4+和 CD11a+/CD4+,B 组与 A 组相比,这些标志物显著增加。在基线和第 24 周时,两组之间 IMT、PWV 和 FMD 无差异。
开始接受基于 PI 的治疗方案会导致第 24 周促动脉粥样硬化生物标志物减少,然后在第 96 周时反弹。与阿扎那韦/利托那韦治疗相比,洛匹那韦/利托那韦治疗导致这些标志物的调节不利。