背景:不断增加的耐药性和缺乏治愈方法,需要探索针对HIV感染者(PLWH)的新治疗策略。靶向可溶性共抑制性免疫检查点分子(sICM)代表了一种新的,艾滋病毒管理中潜在有效的策略。
方法:在本回顾性研究中,纵向,观察性研究,在抗逆转录病毒治疗(ART)之前和之后1年的68例PLWH中,5例显著共抑制性sICMs-CTLA-4,LAG-3,PD-1及其配体PD-L1以及TIM-3-的血浆水平被定量,并与15例健康对照参与者的血浆水平进行比较.
结果:相对于对照参与者,PLWH的所有五种共抑制性sICM的预处理水平均显著升高(p<0.0001-p<0.0657),which,在12个月的ART期间,保持显著高于对照组(p<0.0367-p<0.0001)。PLWH患有晚期疾病,在ART之前,CD4+T细胞计数<200个细胞/mm3,CTLA-4和LAG-3水平最低,而治疗前HIV病毒载量≥100,000拷贝/mL的参与者治疗前TIM-3水平较高,在12个月时也持续.
结论:在未治疗的PLWH中,CTLA-4、LAG-3、PD-1、PD-L1和TIM-3的血浆水平显著升高,并且在一年的病毒抑制性ART后仍然如此。可能确定LAG-3和TIM-3特别是作为辅助免疫疗法的潜在靶标。
BACKGROUND: Increasing drug resistance and the absence of a cure necessitates exploration of novel treatment strategies for people living with HIV (PLWH). Targeting of soluble co-inhibitory immune checkpoint molecules (sICMs) represents a novel, potentially effective strategy in the management of HIV.
METHODS: In this retrospective, longitudinal, observational study, the plasma levels of five prominent co-inhibitory sICMs-CTLA-4, LAG-3, PD-1 and its ligand PD-L1, as well as TIM-3-were quantified in 68 PLWH-before and one year after antiretroviral therapy (ART)-and compared with those of 15 healthy control participants.
RESULTS: Relative to control participants, PLWH had substantially elevated pre-treatment levels of all five co-inhibitory sICMs (p < 0.0001-p < 0.0657), which, over the 12-month period of ART, remained significantly higher than those of controls (p < 0.0367-p < 0.0001). PLWH with advanced disease, reflected by a CD4+ T cell count <200 cells/mm3 before ART, had the lowest levels of CTLA-4 and LAG-3, while participants with pre-treatment HIV viral loads ≥100,000 copies/mL had higher pre-treatment levels of TIM-3, which also persisted at 12 months.
CONCLUSIONS: Plasma levels of CTLA-4, LAG-3, PD-1, PD-L1 and TIM-3 were significantly elevated in treatment-naïve PLWH and remained so following one year of virally-suppressive ART, possibly identifying LAG-3 and TIM-3 in particular as potential targets for adjuvant immunotherapy.