编者按：在第20届欧洲艾滋病大会（EACS 2025）上，《感染医线》特别专访了美国哈佛医学院Janet Lo副教授。第20届欧洲艾滋病大会（EACS 2025）在法国巴黎盛大召开，本届大会以“从科学到实施”（From Science to Implementation）为主题，聚焦艾滋病防治领域的前沿议题。会议期间，《感染医线》特别专访了美国哈佛医学院Janet Lo副教授，就 HIV 感染相关的免疫机制、治疗策略等专业话题展开深入交流。此次专访将为读者呈现国际前沿的学术视角与临床经验，助力业界了解艾滋病防治的最新动态。
01
《感染医线》：CCR2趋化因子受体在动脉粥样硬化的发展中具有重要意义。您能否详细阐述其作用，以及在您的研究中选择靶向CCR2和CCR5的依据？
Janet Lo 副教授
美国哈佛医学院
CCR2趋化因子受体在动脉粥样硬化的发展过程中发挥着关键作用。具体而言，CCR2与其配体MCP1的相互作用，对单核细胞渗出至血管内膜至关重要，这一过程会导致泡沫细胞形成，而泡沫细胞的出现标志着动脉粥样硬化斑块的启动形成。此外，CCR5不仅在动脉粥样硬化发展通路中具有重要作用，还参与了人类免疫缺陷病毒（HIV）感染者的其他炎症通路。
我们的研究旨在验证一项假设，即阻断CCR2和CCR5可减轻动脉炎症，并最终缓解动脉粥样硬化性心血管疾病。该研究在美国艾滋病临床试验组（ACTG）网络下开展，覆盖美国19个研究中心。我们采用CCR2/CCR5受体拮抗剂Cenicriviroc，通过一项随机、双盲、安慰剂对照试验对上述假设进行了验证。然而，研究结果显示，与安慰剂相比，Cenicriviroc并未如最初假设的那样减轻动脉炎症。
IDF: The CCR2 chemokine receptor is very important in the development of atherosclerosis. Could you elaborate on its role and the rationale for targeting CCR2 and CCR5 in your study?
Dr. Janet Lo: The CCR2 chemokine receptor plays a crucial role in the development of atherosclerosis. Specifically, the interaction between CCR2 and its ligand MCP1 is essential for the diapedesis of monocytes into the vascular intima—this process leads to the formation of foam cells, which marks the initiation of atherosclerotic plaque. Additionally, CCR5 is not only important in the atherosclerotic development pathway but also involved in other inflammatory pathways in people living with HIV.
We aimed to test the hypothesis that blocking CCR2 and CCR5 could reduce arterial inflammation and, ultimately, mitigate atherosclerotic cardiovascular disease. Our study was conducted within the ACTG network across 19 sites in the United States. We tested our hypothesis using Cenicriviroc, a CCR2/CCR5 receptor antagonist, in a randomized, double-blind, placebo-controlled trial. However, we found that Cenicriviroc did not reduce arterial inflammation as initially hypothesized, compared to placebo.
02
《感染医线》：从内分泌学视角来看，您对HIV感染者的代谢并发症有哪些担忧？
Janet Lo 副教授
美国哈佛医学院
作为一名内分泌科医生，我对HIV感染者的胰岛素抵抗和血脂异常问题尤为关注。考虑到该人群中糖尿病、胰岛素抵抗和肥胖的患病率正不断上升，这一担忧显得更为关键。此外，高甘油三酯血症和高密度脂蛋白（HDL，即“好胆固醇”）水平偏低的情况，在HIV感染者中也极为常见。所有这些代谢异常都会导致HIV感染者的心血管疾病风险、合并症发生风险以及死亡率显著升高。
IDF: From an endocrinological perspective, what are your concerns regarding metabolic complications in people living with HIV?
Dr. Janet Lo: As an endocrinologist, I am particularly concerned about insulin resistance and dyslipidemia in patients living with HIV. This is especially relevant given the rising prevalence of diabetes, insulin resistance, and obesity in this population. Moreover, hypertriglyceridemia and low HDL levels are highly common among people living with HIV. All these metabolic abnormalities contribute to increased risk of cardiovascular disease, comorbidities, and mortality in patients with HIV.