Service of Immunology and Allergy, Lausanne University Hospital, University of Lausanne, Lausanne, Switzerland.
Curr Opin HIV AIDS. 2022 Sep 1;17(5):325-332. doi: 10.1097/COH.0000000000000751. Epub 2022 Jul 25.
The quest for HIV-1 cure could take advantage of the study of rare individuals that control viral replication spontaneously (elite controllers) or after an initial course of antiretroviral therapy (posttreatment controllers, PTCs). In this review, we will compare back-to-back the immunological and virological features underlying viral suppression in elite controllers and PTCs, and explore their possible contributions to the HIV-1 cure research.
HIV-1 control in elite controllers shows hallmarks of an effective antiviral response, favored by genetic background and possibly associated to residual immune activation. The immune pressure in elite controllers might select against actively transcribing intact proviruses, allowing the persistence of a small and poorly inducible reservoir. Evidence on PTCs is less abundant but preliminary data suggest that antiviral immune responses may be less pronounced. Therefore, these patients may rely on distinct mechanisms, not completely elucidated to date, suppressing HIV-1 transcription and replication.
PTCs and elite controllers may control HIV replication using distinct pathways, the elucidation of which may contribute to design future interventional strategies aiming to achieve a functional cure.
HIV-1 治愈的探索可以利用对自然控制病毒复制的个体(精英控制者)或在初始抗逆转录病毒治疗后控制病毒复制的个体(治疗后控制者,PTCs)的研究。在这篇综述中,我们将比较精英控制者和 PTCs 中病毒抑制的免疫学和病毒学特征,并探讨它们对 HIV-1 治愈研究的可能贡献。
精英控制者中的 HIV-1 控制显示出有效的抗病毒反应的特征,这得益于遗传背景,可能与残留的免疫激活有关。在精英控制者中,免疫压力可能会选择对抗转录完整前病毒,从而允许少量且不易诱导的储库持续存在。关于 PTCs 的证据较少,但初步数据表明,抗病毒免疫反应可能不太明显。因此,这些患者可能依赖于尚未完全阐明的不同机制来抑制 HIV-1 的转录和复制。
PTCs 和精英控制者可能使用不同的途径来控制 HIV 复制,阐明这些途径可能有助于设计未来旨在实现功能性治愈的干预策略。