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PLWH 中基于二药度鲁特韦或三药抗逆转录病毒方案的细胞因子资产。

Cytokines assets in PLWH in two-drug dolutergravir based or three-drug antiretroviral regimen.

机构信息

Clinic of Infectious Diseases, Department of Medicine and Science of Aging, University "G. d'Annunzio", Via dei Vestini, Chieti, 66100, Italy.

Laboratory of Biostatistics, Department of Medical, Oral and Biotechnological Sciences, University "G. D'Annunzio", Via dei Vestini, Chieti, 66100, Italy.

出版信息

BMC Infect Dis. 2024 Jul 3;24(1):665. doi: 10.1186/s12879-024-09565-w.

Abstract

To minimize the toxicity and impact of combined antiretroviral therapy (cART) on the lifestyle of people living with Human Immunodeficiency Virus (PLWH), scientific community evaluated the efficacy, safety and sustained virologic response of two drugs antiretroviral regimens, in particular dolutegravir (DTG). The effects of deintensification therapy on inflammatory settings are currently unknown in PLWH. Thus, our study explored the inflammatory state in virologically suppressed HIV individuals between patients in treatment with a DTG-containing dual therapy (2DR) versus triple regimen therapies (3DR). We enrolled a total of 116 subjects in 2DRs or 3DRs regimens, and the plasma levels of pro- and anti-inflammatory cytokines (in particular IL-1β, IL-10, IL-18, IL-33, IL-36 and IFN-γ) have been evaluated. CD4 + cell's median value was 729.0 cell/µL in the 3DR group and 771.5 cell/µL in 2DR group; the viral load was negative in all patients. Significant differences were found in levels of IL-18 (648.8 cell/µL in 3DR group vs. 475.0 cell/µL in 2DR group, p = 0.034) and IL-36 (281.7 cell/µL in 3DR group vs. 247.0 cell/µL in 2DR group, p = 0.050), and a correlation between IL-18 and IL-36 was found in 3DR group (rho = 0.266, p = 0.015). This single-center retrospective pharmacological study confirms the absence of significant differences in IL-1β, IL-10, IL-33, and IFN-γ levels between patients on two-drug antiretroviral regimens compared to patients on 3DR antiretroviral regimens. Patients in 2DR show greater control over IL-18 and IL-36 serum levels, cytokines related to an increased cardiovascular risk and development of age-related chronic diseases. Based on our results, we suggest that DTG-based 2DR antiretroviral regimens could be associated with better control of the chronic inflammation that characterizes the population living with HIV in effective ART.

摘要

为了最大限度地降低联合抗逆转录病毒疗法(cART)对艾滋病毒感染者(PLWH)生活方式的毒性和影响,科学界评估了两种抗病毒药物治疗方案的疗效、安全性和持续病毒学应答,特别是多替拉韦(DTG)。目前尚不清楚减毒疗法对 PLWH 炎症状态的影响。因此,我们的研究探索了病毒学抑制的 HIV 个体中,接受包含 DTG 的二联治疗(2DR)与三联治疗方案(3DR)的患者之间的炎症状态。我们共纳入了 116 例接受 2DR 或 3DR 方案治疗的患者,并评估了促炎和抗炎细胞因子(特别是 IL-1β、IL-10、IL-18、IL-33、IL-36 和 IFN-γ)的血浆水平。3DR 组 CD4+细胞的中位数为 729.0 个/μL,2DR 组为 771.5 个/μL;所有患者的病毒载量均为阴性。3DR 组 IL-18 水平(648.8 个/μL)与 2DR 组(475.0 个/μL)相比显著升高(p=0.034),IL-36 水平(3DR 组 281.7 个/μL,2DR 组 247.0 个/μL)也有升高趋势(p=0.050),且在 3DR 组中,IL-18 和 IL-36 之间存在相关性(rho=0.266,p=0.015)。这项单中心回顾性药理学研究证实,与接受三药抗逆转录病毒方案治疗的患者相比,接受二药抗逆转录病毒方案治疗的患者在 IL-1β、IL-10、IL-33 和 IFN-γ 水平方面无显著差异。接受二药治疗的患者对血清 IL-18 和 IL-36 水平的控制更好,IL-18 和 IL-36 与心血管风险增加和与年龄相关的慢性疾病发展有关。基于我们的结果,我们建议 DTG 为基础的 2DR 抗逆转录病毒方案可能与更好地控制 HIV 感染者的慢性炎症有关,这种慢性炎症是有效 ART 人群的特征。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/877a/11223302/7126d8825792/12879_2024_9565_Fig1_HTML.jpg

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