Laboratory of Molecular Immunology, The Rockefeller University, New York, NY, USA.
Laboratory of Experimental Immunology, Institute of Virology, University Hospital Cologne, Cologne, Germany.
Nature. 2018 Sep;561(7724):479-484. doi: 10.1038/s41586-018-0531-2. Epub 2018 Sep 26.
Individuals infected with HIV-1 require lifelong antiretroviral therapy, because interruption of treatment leads to rapid rebound viraemia. Here we report on a phase 1b clinical trial in which a combination of 3BNC117 and 10-1074, two potent monoclonal anti-HIV-1 broadly neutralizing antibodies that target independent sites on the HIV-1 envelope spike, was administered during analytical treatment interruption. Participants received three infusions of 30 mg kg of each antibody at 0, 3 and 6 weeks. Infusions of the two antibodies were generally well-tolerated. The nine enrolled individuals with antibody-sensitive latent viral reservoirs maintained suppression for between 15 and more than 30 weeks (median of 21 weeks), and none developed viruses that were resistant to both antibodies. We conclude that the combination of the anti-HIV-1 monoclonal antibodies 3BNC117 and 10-1074 can maintain long-term suppression in the absence of antiretroviral therapy in individuals with antibody-sensitive viral reservoirs.
个体感染 HIV-1 需要终身接受抗逆转录病毒治疗,因为中断治疗会导致病毒迅速反弹。在此,我们报告了一项 1b 期临床试验的结果,该试验中,两种强效的抗 HIV-1 单克隆中和抗体 3BNC117 和 10-1074 联合使用,这两种抗体针对 HIV-1 包膜刺突上的独立位点,在分析性治疗中断期间给药。参与者在 0、3 和 6 周时接受了每公斤 30 毫克的三种抗体输注。两种抗体的输注通常耐受性良好。9 名具有抗体敏感潜伏病毒库的入组个体在 15 周到 30 多周(中位数为 21 周)内保持抑制,且无一例产生对两种抗体均耐药的病毒。我们的结论是,抗 HIV-1 单克隆抗体 3BNC117 和 10-1074 的联合使用可以在具有抗体敏感病毒库的个体中在没有抗逆转录病毒治疗的情况下维持长期抑制。