背景:异基因造血干细胞移植(allo-HSCT)显着减少HIV储库,但是这种情况发生的机制只有部分理解。在这项研究中,我们旨在描述allo-HSCT后HIV持续的病毒学和免疫学标志物的动态。
方法:在这项前瞻性观察队列研究中,我们分析了接受allo-HSCT并接受抗逆转录病毒治疗的IciStemHIV队列参与者的病毒库和血清学动力学,其中10人接受了来自CCR5Δ32突变供体的细胞。来自比利时的与会者,加拿大,德国,意大利,荷兰,西班牙,瑞士,2014年6月1日至2019年4月30日,前瞻性和回顾性地将英国纳入队列.在allo-HSCT后的前6个月,参与者每月进行评估,此后进行年度评估,该协议是为适应每个参与者的个人健康状况而定制的。在血液和组织中测量HIV储库,并在血浆中测量HIV特异性抗体。我们使用Wilcoxon符号秩检验来比较可获得纵向数据的参与者在allo-HSCT之前和之后收集的数据。当配对测试不可能时,我们用了Mann-WhitneyU检验.我们开发了一个数学模型来研究allo-HSCT后HIV感染者中HIV储库减少的影响因素。
结果:我们纳入了30名患有血液恶性肿瘤的HIV患者,他们在2009年9月1日至2019年4月30日之间接受了移植,并纳入了IciStem队列并纳入了该分析。在实现完全供体嵌合后,外周血中的HIV储库立即减少,通常伴有骨髓中检测不到的HIV-DNA,回肠,淋巴结,和脑脊液,无论供体CCR5基因型。HIV特异性抗体水平和功能值比直接HIV储库值下降得更慢。完全供体嵌合体后仅几个月就显著衰退。数学模型表明,供体细胞介导的同种异体免疫是在allo-HSCT(潜伏感染的有复制能力的细胞的半衰期从44个月降低到1·5个月)之前的预处理化疗过程中大量储库减少后的主要病毒储库消耗机制。
结论:我们的工作提供,第一次,关于allo-HSCT在HIV感染背景下的影响的数据。此外,我们提出了一个问题,即哪个标记可以作为残留病毒血症的最后一个报告者,假设在allo-HSCT后,T细胞免疫应答的缺失可能是比抗体下降更可靠的标志物.
背景:amfAR(美国艾滋病研究基金会;ARCHE计划),美国国立卫生研究院,国家过敏和传染病研究所,和荷兰Aidsfonds。
BACKGROUND: Allogeneic haematopoietic stem-cell transplantation (allo-HSCT) markedly reduces HIV reservoirs, but the mechanisms by which this occurs are only partly understood. In this
study, we aimed to describe the dynamics of virological and immunological markers of HIV persistence after allo-HSCT.
METHODS: In this prospective observational cohort
study, we analysed the viral reservoir and serological dynamics in IciStem cohort participants with HIV who had undergone allo-HSCT and were receiving antiretroviral therapy, ten of whom had received cells from donors with the CCR5Δ32 mutation. Participants from Belgium, Canada, Germany, Italy, the Netherlands, Spain, Switzerland, and the UK were included in the cohort both prospectively and retrospectively between June 1, 2014 and April 30, 2019. In the first 6 months after allo-HSCT, participants had monthly assessments, with annual assessments thereafter, with the protocol tailored to accommodate for the individual health status of each participant. HIV reservoirs were measured in blood and tissues and HIV-specific antibodies were measured in plasma. We used the Wilcoxon signed-rank test to compare data collected before and after allo-HSCT in participants for whom longitudinal data were available. When the paired test was not possible, we used the Mann-Whitney U test. We developed a mathematical model to
study the factors influencing HIV reservoir reduction in people with HIV after allo-HSCT.
RESULTS: We included 30 people with HIV with haematological malignancies who received a transplant between Sept 1, 2009 and April 30, 2019 and were enrolled within the IciStem cohort and included in this analysis. HIV reservoirs in peripheral blood were reduced immediately after full donor chimerism was achieved, generally accompanied by undetectable HIV-DNA in bone marrow, ileum, lymph nodes, and cerebrospinal fluid, regardless of donor CCR5 genotype. HIV-specific antibody levels and functionality values declined more slowly than direct HIV reservoir values, decaying significantly only months after full donor chimerism. Mathematical modelling suggests that allogeneic immunity mediated by donor cells is the main viral reservoir depletion mechanism after massive reservoir reduction during conditioning chemotherapy before allo-HSCT (half-life of latently infected replication-competent cells decreased from 44 months to 1·5 months).
CONCLUSIONS: Our work provides, for the first time, data on the effects of allo-HSCT in the context of HIV infection. Additionally, we raise the question of which marker can serve as the last reporter of the residual viraemia, postulating that the absence of T-cell immune responses might be a more reliable marker than antibody decline after allo-HSCT.
BACKGROUND: amfAR (American Foundation for AIDS Research; ARCHE Program), National Institutes of Health, National Institute of Allergy and Infectious Diseases, and Dutch Aidsfonds.