Laboratory of Molecular Immunology, The Rockefeller University, New York, NY.
Department of Physics and Astronomy, University of California, Riverside, CA.
J Exp Med. 2018 Sep 3;215(9):2311-2324. doi: 10.1084/jem.20180936. Epub 2018 Aug 2.
A clinical trial was performed to evaluate 3BNC117, a potent anti-HIV-1 antibody, in infected individuals during suppressive antiretroviral therapy and subsequent analytical treatment interruption (ATI). The circulating reservoir was evaluated by quantitative and qualitative viral outgrowth assay (QVOA) at entry and after 6 mo. There were no significant quantitative changes in the size of the reservoir before ATI, and the composition of circulating reservoir clones varied in a manner that did not correlate with 3BNC117 sensitivity. 3BNC117 binding site amino acid variants found in rebound viruses preexisted in the latent reservoir. However, only 3 of 217 rebound viruses were identical to 868 latent viruses isolated by QVOA and near full-length sequencing. Instead, 63% of the rebound viruses appeared to be recombinants, even in individuals with 3BNC117-resistant reservoir viruses. In conclusion, viruses emerging during ATI in individuals treated with 3BNC117 are not the dominant species found in the circulating latent reservoir, but frequently appear to represent recombinants of latent viruses.
一项临床试验评估了 3BNC117，一种有效的抗 HIV-1 抗体，在接受抑制性抗逆转录病毒治疗和随后的分析性治疗中断（ATI）期间感染个体中的效果。在进入和 6 个月后，通过定量和定性病毒扩增试验（QVOA）评估循环储存库。在 ATI 之前，储存库的大小没有明显的定量变化，并且循环储存库克隆的组成以与 3BNC117 敏感性不相关的方式变化。在反弹病毒中发现的 3BNC117 结合位点氨基酸变体预先存在于潜伏储存库中。然而，在通过 QVOA 和近乎全长测序分离的 217 个潜伏病毒中，只有 3 个与 868 个潜伏病毒相同。相反，63%的反弹病毒似乎是重组病毒，即使在具有 3BNC117 耐药储存库病毒的个体中也是如此。总之，在接受 3BNC117 治疗的个体中，ATI 期间出现的病毒不是在循环潜伏储存库中发现的主要病毒，但经常似乎代表潜伏病毒的重组体。
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