米非司酮抗 HIV 作用的 I/II 期临床试验：HIV 感染者 ACTG 5200 研究

Phase I/II trial of the anti-HIV activity of mifepristone in HIV-infected subjects ACTG 5200.

机构信息

Ohio State University, Columbus, OH, USA.

出版信息

J Acquir Immune Defic Syndr. 2010 Apr 1;53(4):491-5. doi: 10.1097/QAI.0b013e3181d142cb.

DOI:10.1097/QAI.0b013e3181d142cb

PMID:20130470

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC3477637/

Abstract

BACKGROUND

Mifepristone is a glucocorticoid receptor inhibitor shown in vitro to have anti-HIV activity and anti-simian immunodeficiency virus activity in a macaque model. A phase I/II trial was performed to assess the drug's safety and anti-HIV activity.

METHODS

A 28-day double-blind, placebo-controlled trial of mifepristone at doses of 75 mg, 150 mg, and 225 mg given daily was conducted in HIV+ persons with CD4+ lymphocyte counts >or=350 cells per cubic millimeter who had no recent antiretroviral therapy.

RESULTS

Fifty-six male and 1 female subjects with a median entry CD4+ lymphocyte count of 555 cells per cubic millimeter and plasma HIV-1 RNA of 15,623 copies per milliliter were accrued. Forty-five subjects (78.9%) were available for endpoint analysis. In each arm, changes from baseline to day 28 in plasma HIV-1 RNA and CD4+ lymphocyte count were not significantly different from zero (no change). There was no relationship between mifepristone trough concentrations and plasma HIV-1 RNA. Day 28 morning plasma cortisol levels were significantly higher in the 150 mg and 225 mg arms compared with placebo, confirming biologic activity, and returned to baseline by day 56. Serum lipids did not change during the trial. Fasting blood sugar was 2.5 mg/dL higher on day 28 in the mifepristone arms, but the Homeostasis Model Assessment of Insulin Resistance (HOMA-IR) did not change. Three subjects (7.3%) receiving mifepristone developed a grade 2 rash.

CONCLUSIONS

Mifepristone at doses of 75-225 mg daily was safe and well-tolerated, but did not show significant anti-HIV activity.

摘要

背景

米非司酮是一种糖皮质激素受体抑制剂，在体外实验中显示具有抗 HIV 活性和抗猴免疫缺陷病毒活性，并在猕猴模型中得到验证。进行了一项 I/II 期临床试验，以评估该药物的安全性和抗 HIV 活性。

方法

对 CD4+淋巴细胞计数≥350 个/立方毫米且近期未接受抗逆转录病毒治疗的 HIV+患者进行了为期 28 天的双盲、安慰剂对照试验，每日给予米非司酮 75mg、150mg 和 225mg。

结果

共纳入 56 名男性和 1 名女性受试者，中位基线 CD4+淋巴细胞计数为 555 个/立方毫米，血浆 HIV-1 RNA 为 15623 拷贝/毫升。45 名受试者（78.9%）可进行终点分析。在每个治疗组中，从基线到第 28 天血浆 HIV-1 RNA 和 CD4+淋巴细胞计数的变化与零（无变化）无显著差异。米非司酮谷浓度与血浆 HIV-1 RNA 之间无相关性。与安慰剂组相比，150mg 和 225mg 组第 28 天早晨血浆皮质醇水平显著升高，证实了其生物学活性，并在第 56 天恢复至基线。试验期间血清脂质没有变化。米非司酮组第 28 天空腹血糖升高 2.5mg/dL，但稳态模型评估的胰岛素抵抗指数（HOMA-IR）没有变化。3 名（7.3%）接受米非司酮治疗的受试者出现 2 级皮疹。