Interleukin-2 therapy in patients with HIV infection.
Interleukin-2 therapy in patients with HIV infection.
复制标题
DOI：
10.1056/nejmoa0903175
复制
发表时间：
2009-10-15
期刊：
影响因子：
--
通讯作者：
Wentworth D
中科院分区：
文献类型：
--
作者：
INSIGHT-ESPRIT Study Group;SILCAAT Scientific Committee;Abrams D;Lévy Y;Losso MH;Babiker A;Collins G;Cooper DA;Darbyshire J;Emery S;Fox L;Gordin F;Lane HC;Lundgren JD;Mitsuyasu R;Neaton JD;Phillips A;Routy JP;Tambussi G;Wentworth D
与抗逆转录病毒治疗联合使用时，皮下重组白细胞介素-2比单独使用抗逆转录病毒治疗更能提高CD4+细胞计数。这些增加的临床意义尚不清楚。我们进行了两项试验：皮下重组人白细胞介素-2在活性抗逆转录病毒治疗（SILCAAT）下CD4+计数低的hiv感染患者中的研究和皮下白细胞介素原在随机国际试验（ESPRIT）中的评估。在每个病例中，CD4+细胞计数为每立方毫米50 - 299 （SILCAAT）或每立方毫米300或更多（ESPRIT）的感染人类免疫缺陷病毒（HIV）的患者被随机分配接受白细胞介素-2加抗逆转录病毒治疗或单独抗逆转录病毒治疗。白细胞介素-2方案包括连续5天的周期，每8周给药一次。SILCAAT研究涉及六个周期，剂量为450万国际单位的白介素-2，每天两次；ESPRIT包括三个周期和750万国际单位的剂量，每天两次。建议增加周期以维持CD4+细胞计数高于预定的目标水平。两项研究的主要终点均为机会性疾病或任何原因导致的死亡。在SILCAAT研究中，1695名患者（849名接受白细胞介素-2 +抗逆转录病毒治疗，846名单独接受抗逆转录病毒治疗）的中位CD4+细胞计数为每立方毫米202个细胞；在ESPRIT中，纳入了CD4+细胞计数中位数为每立方毫米457个细胞的4111例患者（2071例接受白细胞介素-2 +抗逆转录病毒治疗，2040例单独接受抗逆转录病毒治疗）。在中位7 - 8年的随访期间，白细胞介素-2组的CD4+细胞计数高于单独接受抗逆转录病毒治疗的组——SILCAAT研究和ESPRIT研究中，CD4+细胞计数平均每立方毫米分别高出53和159个。在SILCAAT研究中，白介素-2联合抗逆转录病毒治疗（与单独抗逆转录病毒治疗相比）的机会性疾病或任何原因死亡的风险比为0.91(95%可信区间[CI]， 0.70至1.18;P = 0.47)，在ESPRIT研究中为0.94 （95% CI， 0.75至1.16;P = 0.55）。在SILCAAT研究中，任何原因导致的死亡和4级临床事件的风险比分别为1.06 （P = 0.73）和1.10 (P = 0.35)，在ESPRIT研究中分别为0.90 （P = 0.42）和1.23 （P = 0.003）。尽管与单独抗逆转录病毒治疗相比，CD4+细胞计数显著且持续增加，但在两项研究中，白细胞介素-2 +抗逆转录病毒治疗均未产生临床益处。（ClinicalTrials.gov编号：NCT00004978 [ESPRIT]和NCT00013611 [SILCAAT研究]）
Used in combination with antiretroviral therapy, subcutaneous recombinant interleukin-2 raises CD4+ cell counts more than does antiretroviral therapy alone. The clinical implication of these increases is not known. We conducted two trials: the Subcutaneous Recombinant, Human Interleukin-2 in HIV-Infected Patients with Low CD4+ Counts under Active Antiretroviral Therapy (SILCAAT) study and the Evaluation of Subcutaneous Proleukin in a Randomized International Trial (ESPRIT). In each, patients infected with the human immunodeficiency virus (HIV) who had CD4+ cell counts of either 50 to 299 per cubic millimeter (SILCAAT) or 300 or more per cubic millimeter (ESPRIT) were randomly assigned to receive interleukin-2 plus antiretroviral therapy or antiretroviral therapy alone. The interleukin-2 regimen consisted of cycles of 5 consecutive days each, administered at 8-week intervals. The SILCAAT study involved six cycles and a dose of 4.5 million IU of interleukin-2 twice daily; ESPRIT involved three cycles and a dose of 7.5 million IU twice daily. Additional cycles were recommended to maintain the CD4+ cell count above predefined target levels. The primary end point of both studies was opportunistic disease or death from any cause. In the SILCAAT study, 1695 patients (849 receiving interleukin-2 plus antiretroviral therapy and 846 receiving antiretroviral therapy alone) who had a median CD4+ cell count of 202 cells per cubic millimeter were enrolled; in ESPRIT, 4111 patients (2071 receiving interleukin-2 plus antiretroviral therapy and 2040 receiving antiretroviral therapy alone) who had a median CD4+ cell count of 457 cells per cubic millimeter were enrolled. Over a median follow-up period of 7 to 8 years, the CD4+ cell count was higher in the interleukin-2 group than in the group receiving antiretroviral therapy alone — by 53 and 159 cells per cubic millimeter, on average, in the SILCAAT study and ESPRIT, respectively. Hazard ratios for opportunistic disease or death from any cause with interleukin-2 plus antiretroviral therapy (vs. antiretroviral therapy alone) were 0.91 (95% confidence interval [CI], 0.70 to 1.18; P = 0.47) in the SILCAAT study and 0.94 (95% CI, 0.75 to 1.16; P = 0.55) in ESPRIT. The hazard ratios for death from any cause and for grade 4 clinical events were 1.06 (P = 0.73) and 1.10 (P = 0.35), respectively, in the SILCAAT study and 0.90 (P = 0.42) and 1.23 (P = 0.003), respectively, in ESPRIT. Despite a substantial and sustained increase in the CD4+ cell count, as compared with antiretroviral therapy alone, interleukin-2 plus antiretroviral therapy yielded no clinical benefit in either study. (ClinicalTrials.gov numbers, NCT00004978 [ESPRIT] and NCT00013611 [SILCAAT study].)