在病毒血症个体中联合使用 HIV-1 广泛中和抗体的安全性和抗病毒活性。
Safety and antiviral activity of combination HIV-1 broadly neutralizing antibodies in viremic individuals.
机构信息
Laboratory of Molecular Immunology, The Rockefeller University, New York, NY, USA.
Laboratory of Experimental Immunology, Institute of Virology, University Hospital Cologne, Cologne, Germany.
出版信息
Nat Med. 2018 Nov;24(11):1701-1707. doi: 10.1038/s41591-018-0186-4. Epub 2018 Sep 26.
Monotherapy of HIV-1 infection with single antiretroviral agents is ineffective because error-prone HIV-1 replication leads to the production of drug-resistant viral variants. Combinations of drugs can establish long-term control, however, antiretroviral therapy (ART) requires daily dosing, can cause side effects and does not eradicate the infection. Although anti-HIV-1 antibodies constitute a potential alternative to ART, treatment of viremic individuals with a single antibody also results in emergence of resistant viral variants. Moreover, combinations of first-generation anti-HIV-1 broadly neutralizing antibodies (bNAbs) had little measurable effect on the infection. Here we report on a phase 1b clinical trial ( NCT02825797 ) in which two potent bNAbs, 3BNC117 and 10-1074, were administered in combination to seven HIV-1 viremic individuals. Infusions of 30 mg kg of each of the antibodies were well-tolerated. In the four individuals with dual antibody-sensitive viruses, immunotherapy resulted in an average reduction in HIV-1 viral load of 2.05 log copies per ml that remained significantly reduced for three months following the first of up to three infusions. In addition, none of these individuals developed resistance to both antibodies. Larger studies will be necessary to confirm the efficacy of antibody combinations in reducing HIV-1 viremia and limiting the emergence of resistant viral variants.
抗 HIV-1 单药治疗是无效的,因为 HIV-1 复制错误导致产生耐药病毒变异株。药物联合治疗可以建立长期控制,但抗逆转录病毒治疗(ART)需要每日给药,会引起副作用,并且不能消除感染。虽然抗 HIV-1 抗体是 ART 的一种潜在替代方法,但用单一抗体治疗病毒血症个体也会导致耐药病毒变异株的出现。此外,第一代抗 HIV-1 广泛中和抗体(bNAbs)的组合对感染几乎没有可衡量的效果。在这里,我们报告了一项 1b 期临床试验(NCT02825797),其中将两种有效的 bNAbs(3BNC117 和 10-1074)联合用于 7 名 HIV-1 病毒血症个体。两种抗体各 30mg/kg 的输注均耐受良好。在 4 名具有双重抗体敏感性病毒的个体中,免疫治疗导致 HIV-1 病毒载量平均降低 2.05 对数拷贝/ml,在首次输注后的三个月内仍显著降低。此外,这些个体均未对两种抗体产生耐药性。需要更大规模的研究来证实抗体组合在降低 HIV-1 病毒血症和限制耐药病毒变异株出现方面的疗效。