Department of Internal Medicine/Infectious Diseases, Cannes General Hospital, 06400 Cannes, France.
Unité de Recherche Clinique Cote d'Azur (UR2CA), URRIS, Centre Hospitalier Universitaire Pasteur 2, 06300 Nice, France.
Viruses. 2022 Apr 28;14(5):927. doi: 10.3390/v14050927.
Objective: Immunadapt is a study evaluating the impact of combination antiretroviral treatment (cART) simplification on immune activation. We previously showed that switching to dual therapies could be associated six months later with macrophage activation. Followup continued up to 24 months after treatment simplification. Materials and Methods: Immunadapt is a prospective single arm study of successfully treated subjects simplifying cART from triple to dual regimens. Before cART change, at 6 months, and between 18 and 24 months following the switch, we measured IP-10, MCP-1, soluble CD14 (sCD14), soluble CD163 (sCD163), and lipopolysaccharide binding protein. Patients were stratified according to lower or greater likelihood of immune activation (CD4 nadir < 200, previous AIDS-defining event or very-low-level viremia during follow-up). Variables were compared using matched Wilcoxon tests. Results: From April 2019 to September 2021, 14 subjects were included (mean age 60 years, 12 men, 26 years since HIV infection, CD4 nadir 302 cells/mm3, 18 years on cART, 53 months on last cART). Twenty-one months following the switch, all but one subject maintained their viral load < 50 cp/mL. One subject had two viral blips. For the entire population, the sCD163 values increased significantly from baseline (+36%, p = 0.003) and from 6 months after the switch. The other markers did not change. After 6 months, the sCD163 increase was more pronounced in subjects with greater likelihood of immune activation (+53% vs. +19%, p = 0.026) Conclusions: cART simplification to dual therapy was associated with macrophage activation despite successful virological control after almost two years’ follow-up. This was more pronounced in those at risk of immune activation.
Immunadapt 是一项评估联合抗逆转录病毒治疗 (cART) 简化对免疫激活影响的研究。我们之前的研究表明,转换为双重疗法可能与六个月后巨噬细胞激活有关。随访持续到治疗简化后 24 个月。
Immunadapt 是一项前瞻性、单臂研究,对成功接受治疗的患者从三联疗法简化为双重疗法。在 cART 改变之前、6 个月时以及转换后 18 至 24 个月时,我们测量了 IP-10、MCP-1、可溶性 CD14(sCD14)、可溶性 CD163(sCD163)和脂多糖结合蛋白。根据 CD4 最低点<200、之前的 AIDS 定义事件或随访期间极低水平病毒血症的可能性,将患者分层。使用匹配的 Wilcoxon 检验比较变量。
从 2019 年 4 月至 2021 年 9 月,共纳入 14 例患者(平均年龄 60 岁,男性 12 例,HIV 感染 26 年,CD4 最低点 302 个细胞/mm3,接受 cART 治疗 18 年,最后一次 cART 治疗 53 个月)。转换后 21 个月,除 1 例患者外,所有患者均维持病毒载量<50 cp/mL。1 例患者有两次病毒突破。对于整个队列,sCD163 值从基线开始显著增加(+36%,p=0.003),并且从转换后 6 个月开始增加。其他标志物没有变化。在免疫激活可能性较高的患者中,sCD163 增加更为明显(+53%比+19%,p=0.026)。
cART 简化为双重治疗与巨噬细胞激活有关,尽管在近两年的随访后病毒学控制成功。在免疫激活风险较高的患者中更为明显。