Human umbilical cord mesenchymal stem cell transfusion in immune non-responders with AIDS: a multicenter randomized controlled trial
Lifeng Wang, Zheng Zhang, Ruonan Xu, Xicheng Wang, Zhanjun Shu, Xiejie Chen, Siyu Wang, Jiaye Liu, Yuanyuan Li, Li Wang, Mi Zhang, Wei Yang, Ying Wang, Huihuang Huang, Bo Tu, Zhiwei Liang, Linghua Li, Jingxin Li, Yuying Hou, Ming Shi, Fu‐Sheng Wang
Abstract
Abstract We examined the safety and efficacy of human umbilical cord mesenchymal stem cell (hUC-MSC) infusion for immune non-responder (INR) patients with chronic HIV-1 infection, who represent an unmet medical need even in the era of efficient antiretroviral therapy (ART). Seventy-two INR patients with HIV were enrolled in this phase II randomized, double-blinded, multicenter, placebo-controlled, dose-determination trial (NCT01213186) from May 2013 to March 2016. They were assigned to receive high-dose (1.5 × 10 6 /kg body weight) or low-dose (0.5 × 10 6 /kg body weight) hUC-MSC, or placebo. Their clinical and immunological parameters were monitored during the 96-week follow-up study. We found that hUC-MSC treatment was safe and well-tolerated. Compared with baseline, there was a statistical increase in CD4+ T counts in the high-dose ( P < 0.001) and low-dose ( P < 0.001) groups after 48-week treatment, but no change was observed in the control group. Kaplan–Meier analysis revealed a higher cumulative probability of achieving an immunological response in the low-dose group compared with the control group (95.8% vs. 70.8%, P = 0.004). However, no significant changes in CD4/CD8+ T counts and CD4/CD8 ratios were observed among the three groups. In summary, hUC-MSC treatment is safe. However, the therapeutic efficacy of hUC-MSC treatment to improve the immune reconstitution in INR patients still needs to be further investigated in a large cohort study.