Serum IgG1 and IgG4 could contribute to partial control of viral rebound in chronically HIV-1 infected patients

DOI for this work is: 10.1097/QAD.0000000000002944
Published in 2021 by Lucia Lopalco et al.
All the enrolled patients studied in this work were previously described in the APACHE study. The study was conducted on HIV chronically infected patients, with HIV-RNA <50 cps/mL for ≥10 years, CD4+ cell count >500 cells/μL and HIV-DNA <100 copies/106 PBMC. The ART regimen in use at the time of ATI was resumed at confirmed viral rebound (CVR, defined as two consecutive HIV-RNA >50 copies/mL). Raw data of clinical data of all described patients are reported in table I of the manuscript. Collection of sera and analysis of both binding antibodies (BAbs) and neutralizing antibodies (NAbs) was performed at three different time points: ATI, CVR and time of viral re-suppression after antiretroviral treatment (ART) resumption. IgG subclasses (IgG1, IgG2, IgG3 and IgG4) from the 4 patients with highest levels of neutralization were found to block viral infection (raw data are reported here in fig 2 Fig3 IgG HIV). All subjects had CVR after ATI at a median time of 21 days (14-56). After ART resumption, all the enrolled subjects achieved HIV-RNA<50 copies/mL in 42 days (21-98) (as shown in fig 1 of the manuscript). We observed a strong increase of either BAbs and NAbs titers from ATI to viral re-suppression in one patient, who showed the longest period of virus undetectability during ATI. In this patient, BAbs and NAbs specifically belonged to both IgG1 and IgG4 subclasses, directed to env antigen. Raw data (fig4 HIV) here reported reports the characterization of antibodies in this patients. Further details are shown in fig 4 of the manuscript.

本研究的DOI编号为：10.1097/QAD.0000000000002944。该研究由Lucia Lopalco等人于2021年发表。本研究中纳入的所有患者均已在APACHE研究中有所描述。研究针对的是慢性HIV感染者，其HIV-RNA水平低于50 cps/mL持续10年以上，CD4+细胞计数超过500个/微升，以及HIV-DNA低于100拷贝/106 PBMC。在急性免疫激增（ATI）发生时使用的抗逆转录病毒治疗（ART）方案在确认病毒反弹（CVR，定义为连续两次HIV-RNA超过50拷贝/mL）后恢复。所有描述患者的临床原始数据报告在文稿的表I中。血清的采集和结合抗体（BAbs）及中和抗体（NAbs）的分析在三个不同的时间点进行：ATI、CVR以及抗逆转录病毒治疗（ART）恢复后的病毒再抑制时间点。来自中和能力最强的4名患者的IgG亚类（IgG1、IgG2、IgG3和IgG4）被发现可以阻断病毒感染（原始数据在本处报告，如图2、图3所示的IgG HIV）。所有受试者在ATI后均出现了CVR，中位时间为21天（14-56天）。在ART恢复后，所有受试者在42天内（21-98天）均达到了HIV-RNA低于50拷贝/mL的水平（如文稿中的图1所示）。我们观察到一名患者在ATI期间的病毒不可检测期最长，其BAbs和NAbs滴度从ATI到病毒再抑制期出现了显著增加。在这名患者中，BAbs和NAbs特异地属于IgG1和IgG4亚类，针对env抗原。本处报告的原始数据（图4 HIV）描述了该患者的抗体特征。更多详细信息请参见文稿中的图4。