Gasca-Capote Carmen, Ruiz-Mateos Ezequiel
Institute of Biomedicine of Seville (IBiS), Virgen del Rocio University Hospital, Spanish National Research Council (CSIC), University of Seville, Clinical Unit of Infectious Diseases, Microbiology and Parasitology, Seville, Spain.
Curr Opin HIV AIDS. 2025 Mar 1;20(2):165-171. doi: 10.1097/COH.0000000000000907. Epub 2025 Jan 17.
To summarize the heterogeneity in the elite controllers population with the aim to identify a compatible profile with a persistent HIV remission, making distinction between persistent elite controllers, people with HIV (PWHIV) who permanently maintain virological control in the absence of antiretroviral treatment (ART), and transient elite controllers, PWHIV who eventually lose virological control. For this purpose, it is important to consider the mechanisms and biomarkers that have previously been associated with the maintenance and loss of the natural virological control.
Transient elite controllers, before losing virological control, exhibit a distinct metabolomic, proteomic, microRNAs (miRNA), immunological and virological profile compared to persistent elite controllers. In addition to a reduced and less polyfunctional HIV-specific T-cell response, transient elite controllers show a greater proportion of intact proviruses integrated into genic regions. In contrast, persistent elite controllers display a privileged HIV-1 reservoir profile with absence of detected intact proviruses or low proportion of clonal intact proviruses preferentially integrated into genomic features associated with HIV-1 transcriptional repression.
According to previous studies, the comprehensive characterization of persistent elite controllers might be crucial to identify other PWHIV with this distinct profile as spontaneously cured.
总结精英控制者群体中的异质性，旨在确定与持续性HIV缓解相匹配的特征，区分持续性精英控制者（即在无抗逆转录病毒治疗[ART]的情况下永久维持病毒学控制的HIV感染者[PWHIV]）和短暂性精英控制者（即最终失去病毒学控制的PWHIV）。为此，重要的是要考虑先前与自然病毒学控制的维持和丧失相关的机制和生物标志物。
与持续性精英控制者相比，短暂性精英控制者在失去病毒学控制之前，表现出独特的代谢组学、蛋白质组学、微小RNA（miRNA）、免疫学和病毒学特征。除了HIV特异性T细胞应答减少且多功能性降低外，短暂性精英控制者还显示出整合到基因区域的完整前病毒比例更高。相比之下，持续性精英控制者呈现出一种特殊的HIV-1储存库特征，未检测到完整前病毒或克隆性完整前病毒比例较低，这些前病毒优先整合到与HIV-1转录抑制相关的基因组特征中。
根据先前的研究，对持续性精英控制者进行全面表征对于识别其他具有这种独特特征的PWHIV是否能自发治愈可能至关重要。
