Hengge U R, Goos M, Esser S, Exner V, Dötterer H, Wiehler H, Borchard C, Müller K, Beckmann A, Eppner M T, Berger A, Fiedler M
Department of Dermatology and Venerology, University of Essen, Germany.
AIDS. 1998 Dec 3;12(17):F225-34.
To determine the immunological, virological and clinical effects of subcutaneous IL-2 in 44 HIV-patients in conjunction with pre-existing tri-therapy (zidovudine, 3TC, saquinavir).
Partially randomized, controlled, prospective trial.
Single center study at tertiary care center.
Sixty four patients (CD4 count 200-500 x 10(6)/l).
Fourty four patients were randomized to receive 5-day cycles of IL-2 (9 Mio IU/d) every 6 weeks (Group A) or whenever the CD4 cell count dropped below the 1.25-fold of baseline (Group B), whereas 20 control patients received the same HAART without IL-2.
The optimal individual treatment interval and the immunological and virological effects of subcutaneously administered IL-2 were analysed. Importantly, the level of cellular in vivo immunity and the frequency of dermatological marker diseases and infectious complications were assessed.
IL-2 was well tolerated although fever, influenza-like symptoms and indurated injection sites were commonly encountered. After 1 year of IL-2, there was a median increase of more than 100 x 10(6)/l CD4 cells in both IL-2 groups in contrast to the controls (P < 0.01, 0.01 and not significant). The median HIV load did not increase either in plasma or in lymph nodes. Lymphocyte activation decreased as assessed by MHC class II (P < 0.001), CD25 (P < 0.001) and CD38 expression (P < 0.005). Although delayed type hypersensitivity against common recall antigens increased in both IL-2 groups, it did not reach statistical significance. However, it is of note, that in 7 of 11 (63.6%) patients delayed type hypersensitivity against recombinant HIV antigens improved significantly. Whereas there was no opportunistic infection in either IL-2 group, three cases of Kaposi's sarcoma occurred in the controls. Dermatological indicator diseases (thrush, condyloma, herpes simplex) were found to occur more frequently in the control group.
Subcutaneous IL-2 in addition to HAART was safe and led to sustained qualitative and quantitative immunological improvements in the majority of patients. Individualisation of therapy intervals further improved the efficacy and tolerance of IL-2.
确定皮下注射白细胞介素-2（IL-2）对44例艾滋病患者的免疫、病毒学及临床效果，这些患者同时接受已有的三联疗法（齐多夫定、拉米夫定、沙奎那韦）。
部分随机、对照、前瞻性试验。
三级医疗中心的单中心研究。
64例患者（CD4细胞计数为200 - 500×10⁶/l）。
44例患者被随机分为两组，A组每6周接受为期5天的IL-2治疗周期（900万国际单位/天），B组在CD4细胞计数降至基线的1.25倍以下时接受治疗，另外20例对照患者接受相同的高效抗逆转录病毒治疗（HAART）但不使用IL-2。
分析皮下注射IL-2的最佳个体治疗间隔以及免疫和病毒学效果。重要的是，评估体内细胞免疫水平以及皮肤标记疾病和感染并发症的发生率。
IL-2耐受性良好，尽管常见发热、流感样症状和注射部位硬结。IL-2治疗1年后，两个IL-2治疗组的CD4细胞中位数增加超过100×10⁶/l，而对照组无此变化（P < 0.01、0.01，另一组无显著差异）。血浆和淋巴结中的HIV载量中位数均未增加。通过MHC II类分子（P < 0.001）、CD25（P < 0.001）和CD38表达评估，淋巴细胞活化降低（P < 0.005）。虽然两个IL-2治疗组对常见回忆抗原的迟发型超敏反应均增加，但未达到统计学意义。然而，值得注意的是，11例患者中有7例（63.6%）对重组HIV抗原的迟发型超敏反应显著改善。两个IL-2治疗组均未发生机会性感染，而对照组发生了3例卡波西肉瘤。皮肤指示疾病（鹅口疮、尖锐湿疣、单纯疱疹）在对照组中更常见。
除HAART外，皮下注射IL-2安全，可使大多数患者在免疫方面实现持续的定性和定量改善。治疗间隔的个体化进一步提高了IL-2的疗效和耐受性。
