Phase 2 gene therapy trial of an anti-HIV ribozyme in autologous CD34+ cells.
Gene transfer has potential as a once-only treatment that reduces viral load, preserves the immune system and avoids lifetime highly active antiretroviral therapy. This study, which is to our knowledge the first randomized, double-blind, placebo-controlled, phase 2 cell-delivered gene transfer clinical trial, was conducted in 74 HIV-1-infected adults who received a tat-vpr-specific anti-HIV ribozyme (OZ1) or placebo delivered in autologous CD34+ hematopoietic progenitor cells. There were no OZ1-related adverse events. There was no statistically significant difference in viral load between the OZ1 and placebo group at the primary end point (average at weeks 47 and 48), but time-weighted areas under the curve from weeks 40-48 and 40-100 were significantly lower in the OZ1 group. Throughout the 100 weeks, CD4+ lymphocyte counts were higher in the OZ1 group. This study indicates that cell-delivered gene transfer is safe and biologically active in individuals with HIV and can be developed as a conventional therapeutic product.
Mitsuyasu
Ronald T
RT
Center for Clinical AIDS Research and Education, University of California-Los Angeles, 9911 West Pico Boulevard, Suite 980, Los Angeles, California 90035, USA. rmitsuya@mednet.ucla.edu
Merigan
Thomas C
TC
Carr
Andrew
A
Zack
Jerome A
JA
Winters
Mark A
MA
Workman
Cassy
C
Bloch
Mark
M
Lalezari
Jacob
J
Becker
Stephen
S
Thornton
Lorna
L
Akil
Bisher
B
Khanlou
Homayoon
H
Finlayson
Robert
R
McFarlane
Robert
R
Smith
Don E
DE
Garsia
Roger
R
Ma
David
D
Law
Matthew
M
Murray
John M
JM
von Kalle
Christof
C
Ely
Julie A
JA
Patino
Sharon M
SM
Knop
Alison E
AE
Wong
Philip
P
Todd
Alison V
AV
Haughton
Margaret
M
Fuery
Caroline
C
Macpherson
Janet L
JL
Symonds
Geoff P
GP
Evans
Louise A
LA
Pond
Susan M
SM
Cooper
David A
DA
D000328:Adult; D018952:Antigens, CD34 / Q000276:immunology*; D001483:Base Sequence; D004311:Double-Blind Method; D005260:Female; D015316:Genetic Therapy; D015658:HIV Infections / Q000628:therapy*; D015497:HIV-1 / Q000235:genetics* / Q000302:isolation & purification; D006801:Humans; D008297:Male; D010919:Placebos; D016337:RNA, Catalytic / Q000235:genetics* / Q000627:therapeutic use; D019562:Viral Load
D018952:Antigens, CD34; D010919:Placebos; D016337:RNA, Catalytic