Severely immunosuppressed
AIDS patients with recurrent
opportunistic infections (OIs) represent an unmet medical need even in the era of antiretroviral
therapy (ART). Here we report the development of a
human leukocyte antigen (HLA)-mismatched allogeneic adaptive immune
therapy (
AAIT) for severely immunosuppressed
AIDS patients. Twelve severely immunosuppressed
AIDS patients with severe OIs were enrolled in this single-arm study. Qualified donors received subcutaneous recombinant
granulocyte-colony-stimulating factor twice daily for 4-5 days to stimulate hematopoiesis. Peripheral blood mononuclear cells were collected from these donors via leukapheresis and transfused into the coupled patients. Clinical, immunological, and virological parameters were monitored during a 12-month follow-up period. We found
AAIT combined with ART was safe and well-tolerated at the examined doses and transfusion regimen in all 12 patients. Improvements in clinical symptoms were evident throughout the study period. All patients exhibited a steady increase of peripheral CD4+ T cells from a median 10.5 to 207.5 cells/μl. Rapid increase in peripheral CD8+ T-cell count from a median 416.5 to 1206.5 cells/μl was found in the first 90 days since initiation of
AAIT. In addition, their inflammatory
cytokine levels and HIV
RNA viral load decreased. A short-term microchimerism with donor cells was found. There were no adverse events associated with
graft-versus-host disease throughout the study period. Overall,
AAIT treatment was safe, and might help severely immunosuppressed
AIDS patients to achieve a better immune restoration. A further clinical trial with control is necessary to confirm the efficacy of
AAIT medication.