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

María Trujillo-Rodríguez, Pompeyo Viciana, Inmaculada Rivas-Jeremías, Ana I Álvarez-Ríos, Antonio Ruiz-García, Olga Espinosa-Ibáñez, Salvador Arias-Santiago, Juliana Martínez-Atienza, Rosario Mata, Olga Fernández-López, Ezequiel Ruiz-Mateos, Alicia Gutiérrez-Valencia, Luis F López-Cortés, María Trujillo-Rodríguez, Pompeyo Viciana, Inmaculada Rivas-Jeremías, Ana I Álvarez-Ríos, Antonio Ruiz-García, Olga Espinosa-Ibáñez, Salvador Arias-Santiago, Juliana Martínez-Atienza, Rosario Mata, Olga Fernández-López, Ezequiel Ruiz-Mateos, Alicia Gutiérrez-Valencia, Luis F López-Cortés

Abstract

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.

Trial registration: ClinicalTrials.gov NCT02290041.

Keywords: HIV infection; clinical trial; immunological nonresponders; mesenchymal stromal cells.

Conflict of interest statement

The authors declared no potential conflicts of interest.

© 2020 The Authors. STEM CELLS TRANSLATIONAL MEDICINE published by Wiley Periodicals LLC on behalf of AlphaMed Press.

Figures

FIGURE 1
FIGURE 1
Scheme of visits, infusions of Ad‐MSCs, and sampling time points. *, safety visits, 1 week before the next Ad‐MSC infusion. Ad‐MSC, adipose tissue allogeneic adult mesenchymal stromal cells
FIGURE 2
FIGURE 2
Evolution of the CD4+ T‐cell counts, percentages, and CD4+/CD8+ ratios after 96 weeks of follow‐up. IQR, interquartile range

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