Antiretroviral-free HIV-1 remission and viral rebound after allogeneic stem cell transplantation: report of 2 cases.
Antiretroviral-free HIV-1 remission and viral rebound after allogeneic stem cell transplantation: report of 2 cases.
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DOI：
10.7326/m14-1027
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发表时间：
2014-09-02
影响因子：
39.2
通讯作者：
Kuritzkes DR
中科院分区：
文献类型：
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作者：
Henrich TJ;Hanhauser E;Marty FM;Sirignano MN;Keating S;Lee TH;Robles YP;Davis BT;Li JZ;Heisey A;Hill AL;Busch MP;Armand P;Soiffer RJ;Altfeld M;Kuritzkes DR
同种异体造血干细胞移植（HSCT）后观察到的HIV-1储存库的减少是否足以实现持续的HIV-1缓解尚不清楚。表征血液和组织中的HIV-1储存库，并进行抗逆转录病毒治疗中断分析，以确定同种异体造血干细胞移植导致持续无抗逆转录病毒的HIV-1缓解的潜力。抗逆转录病毒中断前后HIV-1储存库和免疫的特征。三级保健中心。两名hiv感染的男性在接受同种异体造血干细胞移植治疗血液恶性肿瘤后检测不到HIV-1。HSCT后各种组织中HIV-1的定量和治疗中断后无抗逆转录病毒HIV-1缓解的持续时间。在分析性治疗中断前，外周血或直肠粘膜未检测到HIV-1。血浆HIV-1 RNA和细胞相关的HIV-1 DNA直到停止抗逆转录病毒治疗后12至32周仍无法检测到。在最近一次病毒载量检测呈阴性后的一至两周内，两名患者均出现了反跳病毒血症，并发急性逆转录病毒综合征。一名患者在重新开始抗逆转录病毒治疗后出现新的依非韦伦耐药。重新开始积极治疗导致两名患者的病毒衰减和症状缓解。该研究仅限于2例患者。同种异体造血干细胞移植可能导致血液和肠道组织中可检测到的HIV-1的丢失，以及无抗逆转录病毒的HIV-1缓解的不同时期，但病毒反弹可能发生，尽管储存库大小至少减少3-log10。长寿命的组织储存库可能有助于病毒的持久性。确定这些储存库的性质和半衰期对于实现持久的无抗逆转录病毒的HIV-1缓解至关重要。
It is unknown if the reduction in HIV-1 reservoirs observed following allogeneic hematopoietic stem cell transplantation (HSCT) with susceptible donor cells is sufficient to achieve sustained HIV-1 remission. To characterize HIV-1 reservoirs in blood and tissues, and to perform analytical antiretroviral treatment interruptions to determine the potential for allogeneic HSCT to lead to sustained antiretroviral-free HIV-1 remission. Characterization of HIV-1 reservoirs and immunity before and after antiretroviral interruption. Tertiary care center. Two HIV-infected men with undetectable HIV-1 following allogeneic HSCT for hematologic malignancies. Quantification of HIV-1 in various tissues after HSCT and the duration of antiretroviral-free HIV-1 remission after treatment interruption. No HIV-1 was detected from peripheral blood or rectal mucosa prior to analytical treatment interruption. Plasma HIV-1 RNA and cell-associated HIV-1 DNA remained undetectable until 12 to 32 weeks after antiretroviral cessation. Both patients experienced rebound viremia with the development of acute retroviral syndrome within one to two weeks of the most recent negative viral load measurement. One patient developed new efavirenz resistance after re-initiation of antiretroviral therapy. Re-initiation of active therapy led to viral decay and resolution of symptoms in both patients. The study was limited to 2 patients. Allogeneic HSCT may lead to loss of detectable HIV-1 from blood and gut tissue and variable periods of antiretroviral-free HIV-1 remission, but viral rebound can occur despite a minimum 3-log10 reduction in reservoir size. Long-lived tissue reservoirs may have contributed to viral persistence. Defining the nature and half-life of such reservoirs is essential in order to achieve durable antiretroviral-free HIV-1 remission.