Disease: Human Immunodeficiency Virus Infection, HIV, (NCT03666871)
Human immunodeficiency virus (HIV) is a virus that attacks the immune system by infecting and killing white blood cells known as CD4+ T-cells. CD4+ T-cells represent a vital part of the immune system and untreated HIV infections render patients more vulnerable to dangerous infections by other pathogens, including bacteria and fungi. If the virus remains untreated it can lead to patients developing the life-threatening disease acquired immunodeficiency syndrome (AIDS). Untreated HIV can leave people vulnerable to life-threatening infections. HIV symptoms often manifest as flu-like symptoms such as fever, chills, rash, night sweats, muscle aches, sore throat, and fatigue. Today, antiviral medications can allow people living with HIV to live healthy lives.
In 2021, 36,136 people received an HIV diagnosis in the United States and dependent areas. An estimated 1.2 million people in the United States had HIV at the end of 2021.
T-Cell Reinfusion After Interfering With Lymphocyte Binding Location of AIDS Virus Through Zinc-finger-nuclease Elimination of CCR5 Receptors: The TRAILBLAZER Study
Principal Investigator: Carl J. Fichtenbaum, University of Cincinnati
A Comparative Study of Autologous CD4+ T Cells Genetically Modified at the CCR5 Gene by Zinc Finger Nucleases SB-728 versus ex vivo Expanded Unmodified Autologous CD4+ T Cells in Treated HIV-1 Infected Subjects
This is a randomized clinical trial comparing the effect of infusing expanded autologous CD4+ T cells with or without ex vivo modification of the CCR5 gene by zinc finger nucleases among HIV-infected patients with plasma HIV RNA levels <50 copies/mL for at least 48 weeks and CD4+ T cell counts greater than 350 cells/µL. The main hypothesis is that the infusion of modified CD4+ T cells will lead to a reduction in the size of the replication-competent HIV reservoir, as measured by the quantitative virus outgrowth assay (QVOA) that is greater than that resulting from infusion of unmodified CD4+ T cells. A total of 30 participants will be randomized to receive one infusion of 0.5 - 4 x 1010 ex vivo expanded autologous CD4+ T cells that have been either modified by transduction with a zinc finger nuclease designed to cleave CCR5 (arm 1, n=20) or unmodified (arm 2, n=10). All participants will be pre-treated with cyclophosphamide at a dose of 1 g/m2 before infusion. The primary outcome measure will be the change in the number of infectious units per million (IUPM) CD4+ T cells from study enrollment to 24 months after infusion of expanded CD4+ T cells.