title: Gene transfer in humans using a conditionally replicating lentiviral vector.
abstract: We report findings from a clinical evaluation of lentiviral vectors in a phase I open-label nonrandomized clinical trial for HIV. This trial evaluated the safety of a conditionally replicating HIV-1-derived vector expressing an antisense gene against the HIV envelope. Five subjects with chronic HIV infection who had failed to respond to at least two antiviral regimens were enrolled. A single i.v. infusion of gene-modified autologous CD4 T cells was well tolerated in all patients. Viral loads were stable, and one subject exhibited a sustained decrease in viral load. CD4 counts remained steady or increased in four subjects, and sustained gene transfer was observed. Self-limiting mobilization of the vector was observed in four of five patients. There is no evidence for insertional mutagenesis after 21-36 months of observation. Immune function improved in four subjects. Lentiviral vectors appear promising for gene transfer to humans.
authors.affiliation: Abramson Family Cancer Research Institute, University of Pennsylvania Cancer Center, Department of Pathology and Laboratory Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
authors.forename: Bruce L
authors.initials: BL
authors.lastname: Levine
authors.forename: Laurent M
authors.initials: LM
authors.lastname: Humeau
authors.forename: Jean
authors.initials: J
authors.lastname: Boyer
authors.forename: Rob-Roy
authors.initials: RR
authors.lastname: MacGregor
authors.forename: Tessio
authors.initials: T
authors.lastname: Rebello
authors.forename: Xiaobin
authors.initials: X
authors.lastname: Lu
authors.forename: Gwendolyn K
authors.initials: GK
authors.lastname: Binder
authors.forename: Vladimir
authors.initials: V
authors.lastname: Slepushkin
authors.forename: Franck
authors.initials: F
authors.lastname: Lemiale
authors.forename: John R
authors.initials: JR
authors.lastname: Mascola
authors.forename: Frederic D
authors.initials: FD
authors.lastname: Bushman
authors.forename: Boro
authors.initials: B
authors.lastname: Dropulic
authors.forename: Carl H
authors.initials: CH
authors.lastname: June
mesh_terms: D000328:Adult; D018014:Gene Transfer Techniques; D005822:Genetic Vectors / Q000235:genetics*; D015497:HIV-1 / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D006801:Humans; D016086:Lentivirus / Q000502:physiology*; D008875:Middle Aged; D014759:Viral Envelope Proteins / Q000235:genetics / Q000378:metabolism; D014779:Virus Replication / Q000235:genetics*
chemical_list: D014759:Viral Envelope Proteins