IrsiCaixa AIDS Research Institute and Institute for Health Science Research Germans Trias i Pujol (IGTP), Badalona, Spain; Autonomous University of Barcelona, Cerdanyola del Vallés, Spain.
IrsiCaixa AIDS Research Institute and Institute for Health Science Research Germans Trias i Pujol (IGTP), Badalona, Spain.
EBioMedicine. 2020 Jul;57:102830. doi: 10.1016/j.ebiom.2020.102830. Epub 2020 Jun 21.
BACKGROUND: Small viral reservoirs are found predominantly in HIV-1 controllers and individuals treated during acute/early HIV-1 infection. However, other HIV individuals could naturally also harbour low viral reservoirs. METHODS: We screened 451 HIV-1-infected treated-individuals with suppressed plasma viremia for at least 3 years and stored cryopreserved peripheral blood mononuclear cells (PBMCs). Total HIV-DNA was analysed in PBMCs with ddPCR. Individuals with <50 HIV-DNA copies/10 PBMCs constitute the 'Low Viral Reservoir Treated' cohort (LoViReT). Longitudinal samples were obtained from 12 chronically treated LoViReT and compared to 13 controls (>50 HIV-DNA copies/10 PBMCs) to analyse total HIV-DNA, T-cell and NK-cell populations, HIV-1 specific antibodies, and plasma inflammation markers. FINDINGS: We found that 9.3% of the individuals screened had <50 HIV-DNA copies/10 PBMCs. At least 66% initiated cART during the chronic phase of HIV-1 infection (cp-LoViReT). Cp-LoViReT harboured lower levels of HIV-DNA before cART and after treatment introduction the decays were greater compared to controls. They displayed a marked decline in quantity and avidity in HIV-specific antibodies after initiation of cART. Cp-LoViReT had fewer CD8 T and T in the absence of cART, and higher CD8 T after 18 months on therapy. INTERPRETATION: Treated chronically HIV-1-infected LoViReT represent a new phenotype of individuals characterized by an intrinsically reduced viral reservoir, less impaired CD8 T-cell compartment before cART, and low circulating HIV-1 antigens despite being treated in the chronic phase of infection. The identification of this unique group of individuals is of great interest for the design of future eradication studies. FUNDING: MSD Spain.
背景:小病毒库主要存在于 HIV-1 控制器和急性/早期 HIV-1 感染期间接受治疗的个体中。然而,其他 HIV 个体也可能自然地携带低病毒库。
方法:我们筛选了 451 名接受治疗的 HIV-1 感染个体,这些个体的血浆病毒载量已被抑制至少 3 年,并储存了冷冻保存的外周血单核细胞 (PBMC)。使用 ddPCR 分析 PBMC 中的总 HIV-DNA。HIV-DNA<50 拷贝/10 PBMC 的个体构成“低病毒库治疗”队列 (LoViReT)。从 12 名慢性治疗的 LoViReT 中获得纵向样本,并与 13 名对照(HIV-DNA>50 拷贝/10 PBMC)进行比较,以分析总 HIV-DNA、T 细胞和 NK 细胞群体、HIV-1 特异性抗体和血浆炎症标志物。
发现:我们发现筛选的个体中有 9.3%的 HIV-DNA<50 拷贝/10 PBMC。至少有 66%的个体在 HIV-1 感染的慢性期(cp-LoViReT)开始接受 cART。cp-LoViReT 在接受 cART 前的 HIV-DNA 水平较低,并且在治疗开始后,其衰减幅度大于对照。与对照相比,他们在开始接受 cART 后,HIV 特异性抗体的数量和亲和力明显下降。cp-LoViReT 在没有 cART 的情况下 CD8 T 和 T 细胞较少,在接受治疗 18 个月后 CD8 T 细胞较多。
解释:慢性 HIV-1 感染的 LoViReT 代表了一种新的表型个体,其特征是内在的病毒库减少,在接受 cART 之前 CD8 T 细胞区室受损程度较小,并且尽管在感染的慢性期接受治疗,但循环 HIV-1 抗原水平较低。鉴定这群独特的个体对于未来的清除研究设计具有重要意义。
资助:MSD 西班牙。
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