Pappas Peter G, Bustamante Beatriz, Ticona Eduardo, Hamill Richard J, Johnson Philip C, Reboli Annette, Aberg Judith, Hasbun Rodrigo, Hsu Henry H
University of Alabama School of Medicine, Birmingham, Alabama 35294-0006, USA.
J Infect Dis. 2004 Jun 15;189(12):2185-91. doi: 10.1086/420829. Epub 2004 May 24.
We conducted a phase 2, double-blind, placebo-controlled study to evaluate the safety and antifungal activity of adjuvant recombinant interferon (rIFN)- gamma 1b in patients with acquired immunodeficiency syndrome and acute cryptococcal meningitis. Patients received 100 or 200 microg of rIFN- gamma 1b or placebo, thrice weekly for 10 weeks, plus standard therapy with intravenous amphotericin B, with or without flucytosine, followed by therapy with fluconazole. End points included conversion of cerebrospinal fluid fungal cultures from positive to negative at 2 weeks, resolution of symptoms, and survival. Among 75 patients, 2-week culture conversion occurred in 13% of placebo recipients, 36% of rIFN- gamma 1b (100 microg) recipients, and 32% of rIFN- gamma 1b (200 microg) recipients. There was a trend toward improved combined mycologic and clinical success in rIFN- gamma 1b recipients (26% vs. 8%; P=.078). Therapy with rIFN- gamma 1b was well tolerated, and there was no apparent influence on serial CD4 cell counts and human immunodeficiency virus load measurements. Adjunctive therapy with rIFN- gamma 1b holds promise for patients with acute cryptococcal meningitis and warrants further study.
我们开展了一项2期双盲安慰剂对照研究,以评估辅助性重组干扰素(rIFN)-γ1b在获得性免疫缺陷综合征合并急性隐球菌性脑膜炎患者中的安全性和抗真菌活性。患者接受100或200微克rIFN-γ1b或安慰剂治疗,每周3次,共10周,同时接受静脉注射两性霉素B的标准治疗,可联合或不联合氟胞嘧啶,随后接受氟康唑治疗。终点指标包括2周时脑脊液真菌培养结果由阳性转为阴性、症状缓解和生存情况。75例患者中,安慰剂组2周培养转阴率为13%,rIFN-γ1b(100微克)组为36%,rIFN-γ1b(200微克)组为32%。rIFN-γ1b治疗组在真菌学和临床综合疗效改善方面有一定趋势(26%对8%;P = 0.078)。rIFN-γ1b治疗耐受性良好,对连续CD4细胞计数和人类免疫缺陷病毒载量测量无明显影响。rIFN-γ1b辅助治疗对急性隐球菌性脑膜炎患者有前景,值得进一步研究。