Research Centre of the Centre Hospitalier de l'Université de Montréal (CRCHUM), Montreal, QC, Canada.
Université de Montréal, Montreal, QC, Canada.
Nat Med. 2020 Feb;26(2):222-227. doi: 10.1038/s41591-019-0747-1. Epub 2020 Feb 3.
Combination antiretroviral therapy (ART) is highly effective in controlling human immunodeficiency virus (HIV)-1 but requires lifelong medication due to the existence of a latent viral reservoir. Potent broadly neutralizing antibodies (bNAbs) represent a potential alternative or adjuvant to ART. In addition to suppressing viremia, bNAbs may have T cell immunomodulatory effects as seen for other forms of immunotherapy. However, this has not been established in individuals who are infected with HIV-1. Here, we document increased HIV-1 Gag-specific CD8 T cell responses in the peripheral blood of all nine study participants who were infected with HIV-1 with suppressed blood viremia, while receiving bNAb therapy during ART interruption. Increased CD4 T cell responses were detected in eight individuals. The increased T cell responses were due both to newly detectable reactivity to HIV-1 Gag epitopes and the expansion of pre-existing measurable responses. These data demonstrate that bNAb therapy during ART interruption is associated with enhanced HIV-1-specific T cell responses. Whether these augmented T cell responses can contribute to bNAb-mediated viral control remains to be determined.
联合抗逆转录病毒疗法(ART)在控制人类免疫缺陷病毒(HIV-1)方面非常有效,但由于潜伏病毒库的存在,需要终身服药。强效广谱中和抗体(bNAb)代表了一种替代或辅助 ART 的潜在方法。除了抑制病毒血症外,bNAb 可能具有 T 细胞免疫调节作用,就像其他形式的免疫疗法一样。然而,这在感染 HIV-1 的个体中尚未得到证实。在这里,我们记录了在接受 ART 中断期间接受 bNAb 治疗的所有 9 名 HIV-1 感染且血液病毒载量受到抑制的研究参与者的外周血中 HIV-1 Gag 特异性 CD8 T 细胞反应增加。在 8 名个体中检测到 CD4 T 细胞反应增加。增加的 T 细胞反应既归因于新可检测到的对 HIV-1 Gag 表位的反应,也归因于先前可测量的反应的扩增。这些数据表明,ART 中断期间的 bNAb 治疗与增强的 HIV-1 特异性 T 细胞反应相关。这些增强的 T 细胞反应是否可以有助于 bNAb 介导的病毒控制还有待确定。