Davey R T, Murphy R L, Graziano F M, Boswell S L, Pavia A T, Cancio M, Nadler J P, Chaitt D G, Dewar R L, Sahner D K, Duliege A M, Capra W B, Leong W P, Giedlin M A, Lane H C, Kahn J O
National Institutes of Health, Bethesda, MD 20892-1880, USA.
JAMA. 2000 Jul 12;284(2):183-9. doi: 10.1001/jama.284.2.183.
While interleukin 2 (IL-2) is capable of inducing a marked expansion of the CD4 T-lymphocyte pool, limited data exist on whether IL-2 treatment can add significantly to the immunologic and virologic effects of potent antiretroviral therapy (ART).
To determine the rate and magnitude of CD4 cell recovery and viral suppression when using a combination therapy of IL-2 and ART compared with ART alone.
Randomized, controlled multicenter trial conducted from April 1996 through April 1998 at 8 clinical sites in the United States.
Eighty-two adult outpatients who were infected with human immunodeficiency virus (HIV) and had baseline CD4 cell counts of 200 x 10(6)/L to 500 x 10(6)/L and baseline RNA levels of fewer than 10,000 copies/mL were randomized; 78 completed the study.
Thirty-nine patients were randomly assigned to receive a combination therapy of subcutaneous IL-2 (administered in 5-day courses every 8 weeks at a starting dosage of 7.5 mIU twice per day) and ART; 43 were to receive ART therapy alone.
Interleukin 2 safety and differential effects on CD4 cell counts, CD4 cell percentages, and plasma HIV RNA levels.
The mean (SD) percentage increase in CD4 cell counts at 1 year for patients who received IL-2 was 112% (113%) compared with 18% (35%) in recipients of ART alone (P<.001). Both groups had mean (SD) increases in CD4 cell percentage: from 20.4% (6.3%) to 32.3% (12.4%) for the combination therapy group compared with 20.4% (5.1%) to 23.0% (7.2%) for recipients of ART alone (P<.001). Using a sensitive viral RNA assay, mean viral load changes were -0.28 and 0.09 log(10) copies for IL-2 recipients and control patients, respectively (P=.03). Twenty (67%) of 30 evaluable patients receiving IL-2 achieved final viral loads of fewer than 50 copies/mL compared with 13 (36%) of 36 control patients (P=.02). Toxic effects were common among patients who received IL-2 and were managed with antipyretics, hydration, rest, and dosage reduction as needed.
Intermittent therapy with IL-2 and ART produced a substantially greater increase in CD4 cells and was associated with a larger decrease in viral load than ART alone. Clinical end-point trials will be necessary to determine whether the enhanced viral suppression and CD4 cell increases associated with IL-2 therapy will translate into improved clinical outcomes. JAMA. 2000;284:183-189
虽然白细胞介素2（IL-2）能够显著扩大CD4 T淋巴细胞库，但关于IL-2治疗能否显著增强高效抗逆转录病毒疗法（ART）的免疫和病毒学效果的数据有限。
确定与单独使用ART相比，IL-2与ART联合治疗时CD4细胞恢复的速率和幅度以及病毒抑制情况。
1996年4月至1998年4月在美国8个临床地点进行的随机对照多中心试验。
82名感染人类免疫缺陷病毒（HIV）的成年门诊患者，其基线CD4细胞计数为200×10⁶/L至500×10⁶/L，基线RNA水平低于10,000拷贝/mL，被随机分组；78名完成了研究。
39名患者被随机分配接受皮下注射IL-2（每8周进行5天疗程，起始剂量为每天2次，每次7.5 mIU）与ART的联合治疗；43名患者仅接受ART治疗。
白细胞介素2的安全性以及对CD4细胞计数、CD4细胞百分比和血浆HIV RNA水平的差异影响。
接受IL-2治疗的患者在1年时CD4细胞计数的平均（标准差）百分比增加为112%（113%），而单独接受ART治疗的患者为18%（35%）（P<0.001）。两组CD4细胞百分比均有平均（标准差）增加：联合治疗组从20.4%（6.3%）增至32.3%（12.4%），单独接受ART治疗的患者从20.4%（5.1%）增至23.0%（7.2%）（P<0.001）。使用灵敏的病毒RNA检测方法，接受IL-2治疗的患者和对照患者的平均病毒载量变化分别为-0.28和0.09 log₁₀拷贝（P = 0.03）。30名可评估的接受IL-2治疗的患者中有20名（67%）最终病毒载量低于50拷贝/mL，而36名对照患者中有13名（36%）（P = 0.02）。接受IL-2治疗的患者中不良反应常见，通过使用退烧药、补液、休息以及必要时减少剂量进行处理。
与单独使用ART相比，IL-2与ART的间歇治疗使CD4细胞有更大幅度的增加，且病毒载量有更大幅度的下降。需要进行临床终点试验来确定与IL-2治疗相关的增强的病毒抑制和CD4细胞增加是否会转化为改善的临床结局。《美国医学会杂志》。2000年；284:183 - 189
