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在急性感染期而不是早期慢性 HIV-1 感染期开始 cART 治疗 6 个月后,炎症和 T 细胞活化减少。

Reduction of inflammation and T cell activation after 6 months of cART initiation during acute, but not in early chronic HIV-1 infection.

机构信息

Laboratório de Aids e Imunologia Molecular, Instituto Oswaldo Cruz -IOC, FIOCRUZ, Av Brasil, 4365, Pavilhão Leônidas Deane, sala 401, Rio de Janeiro, 21040360, Brazil.

Laboratório de Pesquisa Clínica em DST e Aids, Instituto Nacional de Infectologia Evandro Chagas - INI, FIOCRUZ, Rio de Janeiro, 25984-220, Brazil.

出版信息

Retrovirology. 2018 Dec 12;15(1):76. doi: 10.1186/s12977-018-0458-6.

Abstract

OBJECTIVES

To investigate the impact of early combined antiretroviral therapy (cART) on inflammation biomarkers and immune activation during acute and early chronic HIV-1 infection.

METHODS

We included 12 acute (AHI), 11 early chronic (EcHI), and 18 late chronic HIV-1-infected (LcHI) individuals who were treated with cART and 18 HIV-1-uninfected (HIV-neg) individuals. Plasmatic levels of inflammation biomarkers, CD8CD38HLA-DR T cell frequencies, CD4 T cell counts, CD4/CD8 ratio, total HIV-1 DNA and plasmatic viral load were evaluated. Mann-Whitney test, Pearson and Spearman correlation, and linear regression models were used for statistical analyses.

RESULTS

IP-10, IL-18, and sCD163 were significantly elevated at pre-ART in the AHI and EcHI groups, showing a significant reduction after 6 months of cART in the AHI group, achieving similar levels to the HIV-neg group. For the EcHI group, the IP-10 and sCD163 levels were also significantly reduced on M6-ART; however, IP-10 levels remained higher than in the HIV-neg group, and no significant reduction of IL-18 levels was observed. The CD8 T cell activation levels were elevated in the AHI and EcHI groups at pre-ART and showed a significant reduction on M6-ART, but they were similar to levels seen for HIV-neg only after 12 months of cART. At pre-ART, IP-10 levels but not IL-18 levels were positively correlated with HIV-1 viral load in the AHI group.

CONCLUSIONS

Early initiation of cART in HIV infection can reduce systemic inflammation, but the earlier normalization of the inflammation markers was only observed when cART was initiated in the acute phase of infection. A slower dynamic of reduction was observed for CD8 T cell activation.

摘要

目的

研究早期联合抗逆转录病毒治疗(cART)对急性和早期慢性 HIV-1 感染期间炎症生物标志物和免疫激活的影响。

方法

我们纳入了 12 名急性 HIV-1 感染(AHI)、11 名早期慢性 HIV-1 感染(EcHI)和 18 名晚期慢性 HIV-1 感染(LcHI)患者,他们均接受了 cART 治疗,以及 18 名 HIV-1 未感染(HIV-neg)个体。评估了炎症生物标志物、CD8CD38HLA-DR T 细胞频率、CD4 T 细胞计数、CD4/CD8 比值、总 HIV-1 DNA 和血浆病毒载量的水平。使用曼-惠特尼检验、皮尔逊和斯皮尔曼相关性以及线性回归模型进行统计学分析。

结果

在 AHI 和 EcHI 组的 ART 前,IP-10、IL-18 和 sCD163 显著升高,在 AHI 组 cART 后 6 个月,这些标志物显著降低,达到与 HIV-neg 组相似的水平。对于 EcHI 组,在 M6-ART 时 IP-10 和 sCD163 水平也显著降低;然而,IP-10 水平仍高于 HIV-neg 组,且 IL-18 水平未见明显降低。在 AHI 和 EcHI 组的 ART 前,CD8 T 细胞激活水平升高,在 M6-ART 时显著降低,但仅在 cART 后 12 个月才与 HIV-neg 组相似。在 ART 前,IP-10 水平而非 IL-18 水平与 AHI 组的 HIV-1 病毒载量呈正相关。

结论

在 HIV 感染中早期启动 cART 可降低全身炎症,但仅在感染的急性期启动 cART 时才能更早地使炎症标志物正常化。CD8 T 细胞激活的降低呈现较慢的动态。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d5ca/6291985/925cdf7ae4de/12977_2018_458_Fig1_HTML.jpg

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