Different plasma markers of inflammation are influenced by immune recovery and cART composition or intensification in treated HIV infected individuals.
Different plasma markers of inflammation are influenced by immune recovery and cART composition or intensification in treated HIV infected individuals.
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DOI：
10.1371/journal.pone.0114142
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发表时间：
2014
期刊：
影响因子：
3.7
通讯作者：
Blanco J
中科院分区：
文献类型：
--
作者：
Massanella M;Ouchi D;Marfil S;Llibre JM;Puertas MC;Buzón MJ;Richman DD;Orna E;Stevenson M;Gatell JM;Domingo P;Negredo E;Martinez-Picado J;Clotet B;Blanco J
HIV-1感染会增加炎症标志物的血浆水平。联合抗逆转录病毒治疗（cART）不能将炎症标志物恢复到正常水平。由于在Discor-Ral和IntegRal研究中，雷特格韦强化cART可降低CD 8 T细胞活化，因此我们在这些研究中评估了雷特格韦强化对几种可溶性炎症标志物的影响。对来自IntegRal（n = 67，22个对照和45个强化个体）和Discor-Ral研究（44个CD 4 T细胞计数<350个细胞/μl的个体，14个对照和30个强化个体）的纵向血浆样品（0-48周）进行25种标志物的测定。 采用Mann-Whitney、Wilcoxon、斯皮尔曼检验和线性混合模型进行分析。在基线时，不同的炎症标志物与HCV合并感染、较低的CD 4计数和cART方案（PI治疗个体中较高）密切相关，但与残留病毒复制标志物的检测相关性较差。尽管雷特格韦强化治疗可降低CD 4 T细胞计数较低个体的炎症，但在全球分析中未观察到强化治疗对炎症血浆标志物的影响。然而，发现免疫活化降低与凝血标志物D-二聚体血浆水平之间存在相关性，后者仅在基于蛋白酶抑制剂（PI）的cART方案的强化患者中降低（P = 0.040）。 接受治疗的HIV感染者的炎症特征与HCV合并感染、CD 4 T细胞水平和cART方案存在复杂的相关性。雷特格韦强化治疗特异性降低PI治疗患者的D-二聚体水平，突出了cART组成与残留病毒复制之间的联系;然而，雷特格韦对其他炎症标志物几乎没有影响。
HIV-1 infection increases plasma levels of inflammatory markers. Combination antiretroviral therapy (cART) does not restore inflammatory markers to normal levels. Since intensification of cART with raltegravir reduced CD8 T-cell activation in the Discor-Ral and IntegRal studies, we have evaluated the effect of raltegravir intensification on several soluble inflammation markers in these studies. Longitudinal plasma samples (0–48 weeks) from the IntegRal (n = 67, 22 control and 45 intensified individuals) and the Discor-Ral studies (44 individuals with CD4 T-cell counts<350 cells/µl, 14 control and 30 intensified) were assayed for 25 markers. Mann-Whitney, Wilcoxon, Spearman test and linear mixed models were used for analysis. At baseline, different inflammatory markers were strongly associated with HCV co-infection, lower CD4 counts and with cART regimens (being higher in PI-treated individuals), but poorly correlated with detection of markers of residual viral replication. Although raltegravir intensification reduced inflammation in individuals with lower CD4 T-cell counts, no effect of intensification was observed on plasma markers of inflammation in a global analysis. An association was found, however, between reductions in immune activation and plasma levels of the coagulation marker D-dimer, which exclusively decreased in intensified patients on protease inhibitor (PI)-based cART regimens (P = 0.040). The inflammatory profile in treated HIV-infected individuals showed a complex association with HCV co-infection, the levels of CD4 T cells and the cART regimen. Raltegravir intensification specifically reduced D-dimer levels in PI-treated patients, highlighting the link between cART composition and residual viral replication; however, raltegravir had little effect on other inflammatory markers.
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影响因子：
3.8
作者：
Massanella, Marta;Negredo, Eugenia;Blanco, Julia
通讯作者：
Blanco, Julia
影响因子：
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作者：
Hatano, Hiroyu;Hayes, Timothy L.;Deeks, Steven G.
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Deeks, Steven G.
影响因子：
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作者：
Massanella, Marta;Curriu, Marta;Blanco, Julia
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Blanco, Julia
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通讯作者：
INSIGHT SMART Study Group
影响因子：
3.7
作者：
Cassol E;Misra V;Holman A;Kamat A;Morgello S;Gabuzda D
通讯作者：
Gabuzda D