Immunological and virological study of enfuvirtide-treated HIV-positive patients
Immunological and virological study of enfuvirtide-treated HIV-positive patients
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DOI：
10.1097/01.aids.0000131350.22032.b5
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发表时间：
2004-08-20
期刊：
影响因子：
3.8
通讯作者：
Esté, JA
中科院分区：
文献类型：
--
作者：
Barretina, J;Blanco, J;Esté, JA
目的：评价恩福韦肽（ENF）加优化治疗方案对HIV进入和发病相关的免疫学和病毒学参数的预测价值和演变。方法：在22例患者中进行ENF的III期临床试验亚研究，在基线和第32周测量病毒共受体的使用和对ENF的敏感性，趋化因子，细胞因子和趋化因子受体水平，CD38和HLA-DR表达作为T细胞活化和体外细胞死亡的标志物。结果：包括ENF在内的治疗降低了HIV病毒载量（P < 0.001），并增加了对治疗有反应的患者（n = 14）的CD4细胞计数。RP组CD4细胞CXCR4和CCR5表达显著升高（P < 0.05），趋化因子和白细胞介素-7水平差异无统计学意义。在没有HLA-DR变化的情况下，CD4细胞中CD38表达降低。RP组外周血单个核细胞凋亡明显减少。在基线时分离的病毒的辅助受体使用或ENF敏感性与病毒耐药性或治疗反应无关，这似乎与基线时CD4细胞的激活状态（HLA-DR表达）有关。结论：enf治疗的结果与基线时HIV共受体的使用无关。CD4细胞活化和病毒耐药性是治疗反应的唯一标志。含enf方案诱导的HIV共受体表达发生变化，包括CCR5+CD4+细胞的增加，CD38 T细胞的减少以及T细胞凋亡的减少。(C) 2004利平科特·威廉姆斯·威尔金斯。
Objective: To evaluate the predictive value and evolution of immunological and virological parameters related to HIV entry and pathogenesis in patients receiving enfuvirtide (ENF) plus an optimized regimen.Methods: A phase III clinical trial substudy of ENF in 22 patients measured virus coreceptor use and sensitivity to ENF, levels of chemokines, cytokines and chemokine receptors, CD38 and HLA-DR expression as markers of T cell activation and ex vivo cell death at baseline and at week 32.Results: Treatment including ENF reduced HIV viral load (P < 0.001) and increased the CD4 cell count in patients that responded (RP) to treatment (n = 14). Significant (P < 0.05) increases were noted in the RP group in CXCR4 and CCR5 expression in CD4 cells without major differences in chemokine and interleukin-7 levels. A decrease in CD38 expression in the absence of HLA-DR changes was observed in CD4 cells. Apoptosis of peripheral blood mononuclear cells was significantly reduced in the RP group. Coreceptor use or ENF sensitivity of virus isolated at baseline was not associated with virus resistance or response to treatment, which appeared to be related to the activation state (HLA-DR expression) of CD4 cells at baseline.Conclusion: The outcome of ENF-containing treatment could not be associated with HIV coreceptor use at baseline. CD4 cell activation and viral drug resistance were the only markers of treatment response. Changes induced by ENF-containing regimen were seen in HIV coreceptor expression, including an increase in CCR5+CD4+ cells, a decrease in CD38 T cells and a concomitant reduction of T cell apoptosis. (C) 2004 Lippincott Williams Wilkins.