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抗CD4抗体UB-421对治疗中断后HIV-1反弹的效应
Effect of Anti-CD4 Antibody UB-421 on HIV-1 Rebound after Treatment Interruption


Chang-Yi Wang ... 其他 • 2019.04.18
相关阅读
• 抗CD4抗体可维持对HIV的抑制作用 • 广谱中和抗体在HIV-1预防或免疫治疗中的应用

道阻且长——抗艾滋病的中和抗体之路

 

曹玮,李太生*

中国医学科学院北京协和医院感染科

*通讯作者

 

近30年来,HIV抗病毒治疗已经取得了巨大成就。长期抗病毒治疗能够有效控制感染者体内的病毒复制、延缓疾病进展、显著改善临床预后,但因受限于潜伏病毒储存库的持续存在,目前的药物治疗尚无法完全根除HIV感染。

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摘要


背景

在人类免疫缺陷病毒(HIV)感染者未接受抗逆转录病毒治疗(ART)的情况下,单独给予广泛中和HIV特异性抗体会导致耐抗体病毒的产生。在实施分析性治疗中断(analytic treatment interruption)的HIV感染者中,UB-421(阻断人CD4+ T细胞上病毒结合位点的抗体)有可能诱导持续的病毒学抑制,且不会诱导耐药。

 

方法

我们开展了一项非随机、开放标签、2期临床研究,在实施分析性治疗中断的HIV感染者中评价了UB-421单药治疗的安全性、药代动力学和抗病毒活性。筛选访视时,所有参与者的血浆病毒均不可测(<20 copies HIV RNA/mL)。停用ART后,参与者接受了8次UB-421静脉输入,剂量为每周1次,每次10 mg/kg(队列1),或者每2周1次,每次25 mg/kg(队列2)。主要结局是至病毒反弹(≥400 copies/mL)的时间。

 

结果

本研究共纳入29例参与者,队列1中14例,队列2中15例。在分析性治疗中断期间,UB-421对于所有参与者(研究访视2~9中94.5%的测定值)均维持了病毒学抑制(<20 copies/mL),在8例参与者(28%)中观察到间歇性病毒载量一过性小幅反弹(viral blip)(范围,21~142 copies/mL)。没有任何参与者的血浆病毒反弹至超过400 copies/mL。CD4+ T细胞计数在整个研究期间保持稳定。皮疹(大部分为1级)是常见的一过性不良事件;1例参与者因皮疹停用研究药物。在UB-421单药治疗期间观察到CD4+调节T细胞群减少。

 

结论

在参与者未接受ART的情况下,UB-421(在研究的8~16周)维持了病毒学抑制。1例参与者因皮疹停止治疗(由United Biomedical等资助;在ClinicalTrials.gov注册号为NCT02369146)。





作者信息

Chang-Yi Wang, Ph.D., Wing-Wai Wong, M.D., Hung-Chin Tsai, M.D., Ph.D., Yen-Hsu Chen, M.D., Ph.D., Be-Sheng Kuo, Ph.D., Shugene Lynn, Ph.D., Jana Blazkova, Ph.D., Katherine E. Clarridge, M.D., Hsiao-Wen Su, Ph.D., Chia-Ying Lin, M.S., Fan-Chen Tseng, Ph.D., Annie Lai, M.S., Fu-Hung Yang, M.S., Chen-Han Lin, M.S., William Tseng, M.S., Hsiao-Yi Lin, M.D., Connie L. Finstad, Ph.D., Flossie Wong-Staal, Ph.D., Carl V. Hanson, Ph.D., Tae-Wook Chun, Ph.D., and Mei-June Liao, Ph.D.
From United Biomedical, Hauppauge, NY (C.-Y.W., B.-S.K., C.L.F., F.W.-S.); United Biomedical Asia (C.-Y.W., S.L.) and United BioPharma (C.-Y.W., B.-S.K., H.-W.S., C.-Y.L., F.-C.T., A.L., F.-H.Y., C.-H.L., W.T., M.-J.L.), Hsinchu, Taipei Veterans General Hospital, Taipei (W.-W.W., H.-Y.L.), and Kaohsiung Veterans General Hospital (H.-C.T.) and Kaohsiung Medical University Hospital (Y.-H.C.), Kaohsiung — all in Taiwan; National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD (J.B., K.E.C., T.-W.C.); and the California Department of Public Health, Richmond (C.V.H.). Address reprint requests to Dr. Wang at United Biomedical, 25 Davids Dr., Hauppauge, NY 11788, or at cywang@unitedbiomedical.com. Wing-Wai Wong, M.D., is deceased.

 

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