Immunobiology of HIV, Division of Immunology, Transplantation and Infectious Diseases, San Raffaele Scientific Institute.
Infectious Diseases, San Raffaele Scientific Institute.
AIDS. 2021 Aug 1;35(10):1549-1559. doi: 10.1097/QAD.0000000000002944.
Few studies have investigated chronically infected individuals after antiretroviral therapy (ART) interruption (ATI, analytical therapy interruption); thus, we investigated the association between some HIV-specific antibodies and viral control.
All enrolled patients were previously described in the APACHE study. Briefly, the study was conducted on HIV-1 chronically infected patients, with HIV-RNA less than 50 copies/ml for at least 10 years, CD4+ cell count greater than 500 cells/μl and HIV-DNA less than 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).
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 ART resumption.
IgG subclasses (IgG1, IgG2, IgG3 and IgG4) from the four patients with highest levels of neutralization were found to block viral infection. All patients had CVR after ATI at a median time of 21 days (14-56). After ART resumption, all the enrolled patients achieved HIV-RNA less than 50 copies/ml in 42 days (21-98). 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.
env-specific NAbs and BAbs belonging to IgG1, IgG4 subclasses could be helpful to monitor long-term responses able to control virus replication and eradicate HIV infection.
抗逆转录病毒治疗（ART）中断后（分析性治疗中断，ATI），对慢性感染个体的研究甚少；因此，我们研究了一些 HIV 特异性抗体与病毒控制之间的关联。
所有入组患者均在 APACHE 研究中进行了描述。简要来说，该研究在 HIV-1 慢性感染患者中进行，这些患者的 HIV-RNA 持续 10 年以上小于 50 拷贝/ml，CD4+细胞计数大于 500 个/μl，HIV-DNA 小于 100 拷贝/106 PBMC。ATI 时使用的 ART 方案在确认病毒反弹（CVR，定义为两次连续 HIV-RNA>50 拷贝/ml）时恢复。
在三个不同时间点采集血清并分析结合抗体（BAbs）和中和抗体（NAbs）：ATI、CVR 和 ART 恢复后病毒再抑制时。
发现来自四个中和抗体水平最高的患者的 IgG 亚类（IgG1、IgG2、IgG3 和 IgG4）能够阻断病毒感染。所有患者在 ATI 后中位时间 21 天（14-56 天）发生 CVR。ART 恢复后，所有入组患者在 42 天（21-98 天）内达到 HIV-RNA 小于 50 拷贝/ml。我们观察到一位患者在 ATI 至病毒再抑制期间，其 BAbs 和 NAbs 滴度从 ATI 到病毒再抑制均有强烈增加，且在 ATI 期间病毒检测不到的时间最长。在该患者中，BAbs 和 NAbs 特异性属于 IgG1 和 IgG4 亚类，针对 env 抗原。
属于 IgG1、IgG4 亚类的 env 特异性 NAbs 和 BAbs 可能有助于监测长期反应，从而控制病毒复制并清除 HIV 感染。
