Department of Microbiology and Immunology.
J Infect Dis. 2013 Nov 15;208(10):1613-23. doi: 10.1093/infdis/jit387. Epub 2013 Aug 6.
In treatment-naive, human immunodeficiency virus (HIV)-infected persons, combination antiretroviral therapy (cART) incorporating raltegravir (RAL) is highly effective for virologic suppression, but characteristics of immunologic recovery have not been described.
We performed a 48-week substudy of 15 patients, median age 40 years, within a phase 2 randomized trial of RAL-cART in treatment-naive patients with chronic HIV infection.
Plasma viral load decreased from 5.2 ± 5.3 log10 HIV RNA copies/mL to 2.2 ± 2.4 log10 copies/mL at week 4, reaching <50 copies/mL at week 8 in 13 of 15 patients. Total CD4 T cells increased at week 4, as did central memory CD4 T cells in association with reduction of the immune activation markers HLA-DR and CD38 and immune exhaustion marker PD1 in CD4 and CD8 T cells. Naive CD4 T cells increased at week 24 with appearance of HIV gag-specific interleukin 2, interferon-γ, and CD107a responses in CD4 and CD8 T cells at week 48. Plasma lipopolysaccharide and soluble CD14 decreased, but at week 48 were elevated as compared to healthy volunteers. Altogether, the week 48 immune profile was more favorable in patients taking RAL-cART than in patients treated with non-RAL-cART.
RAL in first-line treatment regimens results in rapid immune reconstitution with residual low-level microbial translocation.
在初治的人类免疫缺陷病毒（HIV）感染者中，包含雷特格韦（RAL）的联合抗逆转录病毒治疗（cART）对于病毒学抑制非常有效，但免疫恢复的特征尚未描述。
我们对 15 名中位年龄为 40 岁的慢性 HIV 感染初治患者进行了一项为期 48 周的 2 期随机试验中 RAL-cART 的亚研究。
血浆病毒载量从 5.2 ± 5.3 log10 HIV RNA 拷贝/mL 降至第 4 周的 2.2 ± 2.4 log10 拷贝/mL，15 名患者中的 13 名在第 8 周达到 <50 拷贝/mL。总 CD4 T 细胞在第 4 周增加，同时中央记忆 CD4 T 细胞增加，与 CD4 和 CD8 T 细胞中免疫激活标志物 HLA-DR 和 CD38 以及免疫耗竭标志物 PD1 的减少相关。幼稚 CD4 T 细胞在第 24 周增加，CD4 和 CD8 T 细胞在第 48 周出现 HIV gag 特异性白细胞介素 2、干扰素-γ 和 CD107a 反应。血浆脂多糖和可溶性 CD14 降低，但在第 48 周与健康志愿者相比升高。总的来说，与接受非 RAL-cART 治疗的患者相比，接受 RAL-cART 一线治疗方案的患者第 48 周的免疫特征更为有利。
RAL 用于一线治疗方案可迅速重建免疫，同时伴有低水平的微生物易位残留。
