Mesenchymal stromal cells in human immunodeficiency virus-infected patients with discordant immune response: Early results of a phase I/II clinical trial

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.