Long-Term Reduction in Peripheral Blood HIV Type 1 Reservoirs Following Reduced-Intensity Conditioning Allogeneic Stem Cell Transplantation
Long-Term Reduction in Peripheral Blood HIV Type 1 Reservoirs Following Reduced-Intensity Conditioning Allogeneic Stem Cell Transplantation
复制标题
DOI：
10.1093/infdis/jit086
复制
发表时间：
2013-06-01
影响因子：
6.4
通讯作者：
Kuritzkes, Daniel R.
中科院分区：
文献类型：
--
作者：
Henrich, Timothy J.;Hu, Zixin;Kuritzkes, Daniel R.
背景。异基因造血干细胞移植 (HSCT) 对接受联合抗逆转录病毒治疗 (cART) 的患者的人类免疫缺陷病毒 1 型 (HIV-1) 储存库的长期影响在很大程度上尚不清楚。方法。我们研究了野生型 CCR5(+) 细胞供体的低强度条件同种异体 HSCT 对 2 名 ccr5 delta 32 突变杂合子患者的 HIV-1 外周血库的影响。对 HSCT 之前和之后 3.5 年内获得的样本进行了外周血中 HIV-1 储存库大小、辅助受体使用和特异性抗体反应的深入分析。结果。尽管在 HSCT 之前和之后 2-3 个月的外周血单核细胞 (PBMC) 中很容易检测到 HIV-1 DNA，但在 HSCT 后 21 和 42 个月，在 PBMC、CD4(+) T 细胞或血浆中检测不到 HIV-1 DNA 和 RNA。可检测到的 HIV-1 的缺失在时间上与完全供体嵌合、移植物抗宿主病的发生以及 HIV 特异性抗体水平的降低相关。结论。供体细胞在没有持续 HIV-1 感染证据的情况下植入的能力表明，HIV-1 复制可能在 cART 期间被完全抑制，并且无助于维持患者外周血中的病毒库。使用野生型 CCR5(+) 供体细胞进行 HSCT 可以持续减少外周 HIV-1 病毒库的大小。
Background. The long-term impact of allogeneic hematopoietic stem cell transplantation (HSCT) on human immunodeficiency virus type 1 (HIV-1) reservoirs in patients receiving combination antiretroviral therapy (cART) is largely unknown.Methods. We studied the effects of a reduced-intensity conditioning allogeneic HSCT from donors with wild-type-CCR5(+) cells on HIV-1 peripheral blood reservoirs in 2 patients heterozygous for the ccr5 delta 32 mutation. In-depth analyses of the HIV-1 reservoir size in peripheral blood, coreceptor use, and specific antibody responses were performed on samples obtained before and up to 3.5 years after HSCT receipt.Results. Although HIV-1 DNA was readily detected in peripheral blood mononuclear cells (PBMCs) before and 2-3 months after HSCT receipt, HIV-1 DNA and RNA were undetectable in PBMCs, CD4(+) T cells, or plasma up to 21 and 42 months after HSCT. The loss of detectable HIV-1 correlated temporally with full donor chimerism, development of graft-versus-host disease, and decreases in HIV-specific antibody levels.Conclusions. The ability of donor cells to engraft without evidence of ongoing HIV-1 infection suggests that HIV-1 replication may be fully suppressed during cART and does not contribute to maintenance of viral reservoirs in peripheral blood in our patients. HSCTs with wild-type-CCR5(+) donor cells can lead to a sustained reduction in the size of the peripheral reservoir of HIV-1.