Reconstitution of HIV-1 reservoir following high-dose chemotherapy/autologous stem cell transplantation for lymphoma.
Reconstitution of HIV-1 reservoir following high-dose chemotherapy/autologous stem cell transplantation for lymphoma.
复制标题
高剂量化疗/淋巴瘤自体干细胞移植后 HIV-1 储存库的重建。
DOI：
10.1097/qad.0000000000002051
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发表时间：
2019
期刊：
影响因子：
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通讯作者：
Delaugerre,Constance
中科院分区：
文献类型：
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作者：
Delagreverie,HéloïseM;Gerard,Laurence;Chaillon,Antoine;Roelens,Marie;Djerroudi,Lounes;Salmona,Maud;Larghero,Jérôme;Galicier,Lionel;Simon,François;Oksenhendler,Eric;Moins-Teisserenc,Hélène;Delaugerre,Constance
目的：大剂量化疗后自体干细胞移植(HDC/ASCT)是研究HDC对HIV-1感染者影响的主要模型。我们分析了HDC/ASCT对复发的贮存库组成和来源的影响。设计：我们纳入了在一个参考中心接受HDC/ASCT治疗的高危淋巴瘤患者的同质性组，采用相似的化疗方案。方法：纳入2012-2015年接受HDC/ASCT治疗的13名参与者。每名参与者的平均纵向血样为7份。用定量聚合酶链式反应检测外周血单个核细胞(PBMC)中HIV-1DNA含量。在六名持续病毒抑制的参与者中，对高度可变的C2V3病毒区域进行了下一代测序。根据重构的病毒单倍型构建最大似然系统发育树。结果：外周血单核细胞相关的HIV-1 DNA水平随时间变化不大。病毒多样性在淋巴瘤治疗过程中下降，但在HDC/ASCT后迅速增加到化疗前的数量。来自所有时间点的血液病毒种群混合在系统发育树中：复活的储存库类似于HDC前循环前病毒。结论：HDC/ASCT后人类免疫缺陷病毒(HIV-1)贮备库的特征揭示了HDC/ASCT后记忆CD4+T细胞快速而稳定的补充。随着HDC/ASCT越来越多地参与基因修饰的造血干细胞治疗HIV的试验，对HIV阳性自体移植中感染的T细胞的管理将是至关重要的。
Objectives:Autologous stem cell transplantation following high-dose chemotherapy (HDC/ASCT) is the prime model to study the impact of HDC in HIV-1-infected participants. We analyzed the impact of HDC/ASCT on the resurgent reservoir composition and origin.Design:We included retrospectively a homogenous group of HIV-1-infected patients treated for high-risk lymphoma in a reference center with similar chemotherapy regimens.Methods:Thirteen participants treated with HDC/ASCT from 2012 to 2015 were included. A median seven longitudinal blood samples per participant were available. Total HIV-1 DNA levels in peripheral blood mononuclear cells (PBMCs) were quantified by quantitative PCR. In six participants with sustained viral suppression, the highly variable C2V3 viral region was subjected to next-generation sequencing. Maximum-likelihood phylogeny trees were generated from the reconstructed viral haplotypes. Lymphocyte subsets were studied by flow cytometry.Results:PBMC-associated HIV-1 DNA levels were stable over time. Viral diversity decreased along lymphoma treatment, but increased promptly back to prechemotherapy numbers after HDC/ASCT. Blood viral populations from all time-points were intermingled in phylogeny trees: the resurgent reservoir was similar to pre-HDC circulating proviruses. Memory subsets were the main contributor to the early restoration of the CD4+ T-cell pool, with a delayed increase in naïve cell counts.Conclusions:The characterization of HIV-1 reservoir in blood revealed a fast and consistent replenishment from memory CD4+ T cells after HDC/ASCT. As HDC/ASCT is increasingly involved in HIV cure trials with gene-modified hematopoietic stem cells, the management of infected T cells in HIV-positive autologous transplants will be critical.