St. Michael's Hospital Division of Infectious Diseases, Toronto, ON, Canada.
University Health Network Division of Infectious Diseases, Toronto, ON, Canada.
PLoS One. 2019 Sep 6;14(9):e0221653. doi: 10.1371/journal.pone.0221653. eCollection 2019.
Inflammation has been associated with increased morbidity and mortality in HIV-positive patients. We compared inflammatory biomarkers with dual therapy using lopinavir/ritonavir plus lamivudine (LPV/r+3TC) versus triple therapy using LPV/r plus two nucleoside reverse transcriptase inhibitors (LPV/r+2NRTIs) in treatment-naïve HIV-positive adults.
This was a substudy among Argentinian participants in the randomized trial GARDEL. We measured hsCRP, IL-6, MCP-1, TNF, D-dimer and sCD14 from plasma collected at baseline, week 24 and week 48. Generalized estimating equations with an identity/logit link were used to model the average impact of dual versus triple therapy on each biomarker over time, controlling for baseline levels. Additional models estimated the average effect of virologic suppression on biomarker levels over time, adjusting for age, sex, and baseline CD4 count.
Of 191 trial participants enrolled in Argentina, 172 had baseline and follow-up measurements and were included. Median (IQR) age was 35.5 (28.5, 45) years and CD4 cell count was 310 (219, 414) cells/mm3. Dual therapy was not associated with significantly different biomarker levels over 48 weeks relative to triple therapy. Virologic suppression was associated with statistically significant decreases in MCP-1, TNF and D-dimer levels and an unexpected increase in sCD14 levels. No change was observed in hsCRP or the proportion of participants with undetectable IL-6 levels.
In addition to having virologic non-inferiority, LPV/r+3TC dual therapy is generally associated with similar inflammatory biomarker levels over 48 weeks compared to LPV/r+2NRTIs triple therapy in treatment-naïve adults. Further study of dual treatment regimens is warranted.
炎症与 HIV 阳性患者的发病率和死亡率增加有关。我们比较了使用洛匹那韦/利托那韦加拉米夫定（LPV/r+3TC）的双药治疗与使用 LPV/r 加两种核苷逆转录酶抑制剂（LPV/r+2NRTIs）的三药治疗在初治 HIV 阳性成人中的炎症生物标志物。
这是一项在阿根廷参与随机 GARDEL 试验的亚研究。我们从基线、第 24 周和第 48 周采集的血浆中测量了 hsCRP、IL-6、MCP-1、TNF、D-二聚体和 sCD14。使用具有恒等/对数链接的广义估计方程来模拟双药治疗与三药治疗随时间对每种生物标志物的平均影响，同时控制基线水平。额外的模型估计了病毒学抑制随时间对生物标志物水平的平均影响，同时调整了年龄、性别和基线 CD4 计数。
在阿根廷入组的 191 名试验参与者中，有 172 人有基线和随访测量值并被纳入分析。中位（IQR）年龄为 35.5（28.5，45）岁，CD4 细胞计数为 310（219，414）个细胞/mm3。与三药治疗相比，48 周内双药治疗与生物标志物水平无显著差异。病毒学抑制与 MCP-1、TNF 和 D-二聚体水平的统计学显著下降以及 sCD14 水平的意外升高相关。hsCRP 或无法检测到 IL-6 水平的参与者比例没有变化。
除了具有病毒学非劣效性外，LPV/r+3TC 双药治疗与 LPV/r+2NRTIs 三药治疗相比，在初治成人中，48 周内通常与相似的炎症生物标志物水平相关。需要进一步研究双治疗方案。
