Between 15% and 30% of HIV‐infected subjects fail to increase their CD4⁺ T‐cell counts despite continuous viral suppression (immunological nonresponders [INRs]). These subjects have a higher morbidity and mortality rate, but there are no effective treatments to reverse this situation so far. This study used data from an interrupted phase I/II clinical trial to evaluate safety and immune recovery after INRs were given four infusions, at baseline and at weeks 4, 8, and 20, with human allogeneic mesenchymal stromal cells from adipose tissue (Ad‐MSCs). Based on the study design, the first 5 out of 15 INRs recruited received unblinded Ad‐MSC infusions. They had a median CD4⁺ nadir count of 16/μL (range, 2‐180) and CD4⁺ count of 253 cells per microliter (171‐412) at baseline after 109 (54‐237) months on antiretroviral treatment and 69 (52‐91) months of continuous undetectable plasma HIV‐RNA. After a year of follow‐up, an independent committee recommended the suspension of the study because no increase of CD4⁺ T‐cell counts or CD4⁺/CD8⁺ ratios was observed. There were also no significant changes in the phenotype of different immunological lymphocyte subsets, percentages of natural killer cells, regulatory T cells, and dendritic cells, the inflammatory parameters analyzed, and cellular associated HIV‐DNA in peripheral blood mononuclear cells. Furthermore, three subjects suffered venous thrombosis events directly related to the Ad‐MSC infusions in the arms where the infusions were performed. Although the current study is based on a small sample of participants, the findings suggest that allogeneic Ad‐MSC infusions are not effective to improve immune recovery in INR patients or to reduce immune activation or inflammation. ClinicalTrials.gov identifier: NCT0229004. EudraCT number: 2014‐000307‐26.

中文翻译：

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免疫反应不一致的人类免疫缺陷病毒感染患者的间充质基质细胞：I/II 期临床试验的早期结果

15% 至 30% 的 HIV 感染受试者尽管持续抑制病毒，但未能增加其 CD4 ⁺ T 细胞计数（免疫无反应者 [INR]）。这些受试者的发病率和死亡率较高，但迄今为止还没有有效的治疗方法来扭转这种情况。本研究使用来自中断的 I/II 期临床试验的数据来评估 INR 在基线和第 4、8 和 20 周输注四次后的安全性和免疫恢复，用来自脂肪组织的人类同种异体间充质基质细胞（Ad- MSC）。根据研究设计，招募的 15 名 INR 中的前 5 名接受了非盲注 Ad-MSC。他们的 CD4 ⁺最低点计数中位数为 16/μL（范围，2-180）和 CD4 ⁺在接受抗逆转录病毒治疗 109 (54-237) 个月和连续检测不到血浆 HIV-RNA 69 (52-91) 个月后，基线时每微升 (171-412) 个细胞计数为 253 个细胞。经过一年的随访，一个独立委员会建议暂停该研究，因为 CD4 ⁺ T 细胞计数或 CD4 ⁺ /CD8 ^{+没有增加}观察到比率。不同免疫淋巴细胞亚群的表型、自然杀伤细胞、调节性 T 细胞和树突状细胞的百分比、分析的炎症参数以及外周血单个核细胞中的细胞相关 HIV-DNA 也没有显着变化。此外，三名受试者在进行输注的手臂中遭受与 Ad-MSC 输注直接相关的静脉血栓形成事件。尽管目前的研究是基于一小部分参与者，但研究结果表明，同种异体 Ad-MSC 输注不能有效改善 INR 患者的免疫恢复或减少免疫激活或炎症。ClinicalTrials.gov 标识符：NCT0229004。EudraCT 编号：2014-000307-26。