Cenicriviroc, a dual CCR2 and CCR5 antagonist leads to a reduction in plasma fibrotic biomarkers in persons living with HIV on antiretroviral therapy
Cenicriviroc, a dual CCR2 and CCR5 antagonist leads to a reduction in plasma fibrotic biomarkers in persons living with HIV on antiretroviral therapy
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DOI：
10.1080/25787489.2020.1719319
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发表时间：
2019-09-03
影响因子：
1.6
通讯作者：
Shikuma, C.
中科院分区：
文献类型：
--
作者：
Bowler, S.;Siriwardhana, C.;Shikuma, C.
背景：尽管采用了抑制性抗逆转录病毒治疗（ART），慢性HIV仍与炎症和组织纤维化增加有关。单核细胞和巨噬细胞在趋化因子受体的相互作用下参与纤维化的发病机制。方法：我们在先前发表的一项为期24周的开放标签试验中评估了储存血浆中的系统性纤维化生物标志物（转化生长因子β -1 [tgf - β 1]，血小板反应蛋白-1 [TSP-1]， I型胶原蛋白c末端前肽[CICP]和IL-11）， CVC是一种CCR2/CCR5双拮抗剂，在接受稳定抗逆转录病毒治疗且血浆HIV RNA检测不到的HIV感染者（PLWH）中（0.05），而与对照组相比，PLWH中TSP-1仍升高（p = 0.009）。结论：PLWH具有较高的血浆纤维化标志物tgf - β 1、TSP-1和CICP水平。CVC 24周后，纤维化标志物通常恢复到与未感染hiv的对照组相当的水平。双重阻断CCR2和CCR5可能改善治疗后持续存在的有害纤维化事件。
Background: Chronic HIV is associated with increased inflammation and tissue fibrosis despite suppressive antiretroviral therapy (ART). Monocytes and macrophages have been implicated in the pathogenesis of fibrosis, facilitated by chemokine receptor interactions. Methods: We assessed systemic fibrotic biomarkers (transforming growth factor beta-1 [TGF-beta 1], thrombospondin-1 [TSP-1], C-terminal pro-peptide of collagen type I [CICP], and IL-11) in banked plasma from a previously published 24-week open-label trial of cenicriviroc (CVC), a dual CCR2/CCR5 antagonist, among persons living with HIV (PLWH) on stable ART with undetectable plasma HIV RNA ( 0.05), while TSP-1 remained elevated in PLWH (p = 0.009) compared to controls. Conclusions: PLWH had higher levels of the plasma fibrotic markers TGF-beta 1, TSP-1, and CICP. After 24 weeks of CVC, fibrotic markers generally returned to levels comparable to HIV-uninfected controls. Dual CCR2 and CCR5 blockade may ameliorate the detrimental fibrotic events that persist in treated HIV.