美国国立卫生研究院的Tae-Wook Chun研究团队探明联合抗人类免疫缺陷病毒 (HIV)抗体提供持续的病毒学抑制。2022年6月1日出版的《自然》杂志发表了科学家的一项最新研究成果。
他们报告了一项涉及被动转移两种 HIV 特异性广泛中和单克隆抗体 3BNC117 和 10-1074 的双组分临床试验的结果。第一个组成部分是一项随机、双盲、安慰剂对照试验，该试验招募了在 HIV 感染的急性/早期阶段开始抗逆转录病毒治疗的参与者。第二个组成部分是一项开放标签的单臂试验，该试验招募了未接受过抗逆转录病毒治疗的病毒血症控制者。 3BNC117 和 10-1074 的多达 8 次输注，在 24 周内给药，耐受性良好，没有任何与输注相关的严重不良事件。
与安慰剂相比，广泛中和单克隆抗体的组合在分析治疗中断后可完全抑制血浆病毒血症（长达 43 周），前提是在研究参与者的基线未检测到抗体耐药性 HIV。同样，在基线时携带敏感病毒的病毒血症的未接受抗逆转录病毒治疗的研究参与者中也观察到了有效的 HIV 抑制。他们的数据表明，与广泛中和单克隆抗体的联合治疗可以在没有抗逆转录病毒治疗的情况下对 HIV 感染者提供长期的病毒学抑制，他们的经验为未来涉及具有长半衰期的下一代抗体的临床试验提供指导。
据悉，抗逆转录病毒疗法在抑制HIV方面非常有效。然而，迄今为止还无法根除 HIV 感染者体内的病毒。鉴于抑制 HIV 需要终身抗逆转录病毒治疗，主要是每天进行，因此需要开发临床有效的替代方案，使用长效抗病毒药物来抑制病毒复制。
附：英文原文
Title: Combination anti-HIV antibodies provide sustained virological suppression
Author: Sneller, Michael C., Blazkova, Jana, Justement, J. Shawn, Shi, Victoria, Kennedy, Brooke D., Gittens, Kathleen, Tolstenko, Jekaterina, McCormack, Genevieve, Whitehead, Emily J., Schneck, Rachel F., Proschan, Michael A., Benko, Erika, Kovacs, Colin, Oguz, Cihan, Seaman, Michael S., Caskey, Marina, Nussenzweig, Michel C., Fauci, Anthony S., Moir, Susan, Chun, Tae-Wook
Issue&Volume: 2022-06-01
Abstract: Antiretroviral therapy is highly effective in suppressing human immunodeficiency virus (HIV)1. However, eradication of the virus in individuals with HIV has not been possible to date2. Given that HIV suppression requires life-long antiretroviral therapy, predominantly on a daily basis, there is a need to develop clinically effective alternatives that use long-acting antiviral agents to inhibit viral replication3. Here we report the results of a two-component clinical trial involving the passive transfer of two HIV-specific broadly neutralizing monoclonal antibodies, 3BNC117 and 10-1074. The first component was a randomized, double-blind, placebo-controlled trial that enrolled participants who initiated antiretroviral therapy during the acute/early phase of HIV infection. The second component was an open-label single-arm trial that enrolled individuals with viraemic control who were naive to antiretroviral therapy. Up to 8 infusions of 3BNC117 and 10-1074, administered over a period of 24weeks, were well tolerated without any serious adverse events related to the infusions. Compared with the placebo, the combination broadly neutralizing monoclonal antibodies maintained complete suppression of plasma viraemia (for up to 43weeks) after analytical treatment interruption, provided that no antibody-resistant HIV was detected at the baseline in the study participants. Similarly, potent HIV suppression was seen in the antiretroviral-therapy-naive study participants with viraemia carrying sensitive virus at the baseline. Our data demonstrate that combination therapy with broadly neutralizing monoclonal antibodies can provide long-term virological suppression without antiretroviral therapy in individuals with HIV, and our experience offers guidance for future clinical trials involving next-generation antibodies with long half-lives.
DOI: 10.1038/s41586-022-04797-9
Source: https://www.nature.com/articles/s41586-022-04797-9
Nature：《自然》，创刊于1869年。隶属于施普林格·自然出版集团，最新IF：69.504
官方网址：http://www.nature.com/
投稿链接：http://www.nature.com/authors/submit_manuscript.html
本期文章：《自然》：Online/在线发表
