Gene transfer in humans using a conditionally replicating lentiviral vector.
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.
Levine
Bruce L
BL
Abramson Family Cancer Research Institute, University of Pennsylvania Cancer Center, Department of Pathology and Laboratory Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
Humeau
Laurent M
LM
Boyer
Jean
J
MacGregor
Rob-Roy
RR
Rebello
Tessio
T
Lu
Xiaobin
X
Binder
Gwendolyn K
GK
Slepushkin
Vladimir
V
Lemiale
Franck
F
Mascola
John R
JR
Bushman
Frederic D
FD
Dropulic
Boro
B
June
Carl H
CH
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*
D014759:Viral Envelope Proteins