title: Phase 2 gene therapy trial of an anti-HIV ribozyme in autologous CD34+ cells.
abstract: 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.
authors.affiliation: 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
authors.forename: Ronald T
authors.initials: RT
authors.lastname: Mitsuyasu
authors.forename: Thomas C
authors.initials: TC
authors.lastname: Merigan
authors.forename: Andrew
authors.initials: A
authors.lastname: Carr
authors.forename: Jerome A
authors.initials: JA
authors.lastname: Zack
authors.forename: Mark A
authors.initials: MA
authors.lastname: Winters
authors.forename: Cassy
authors.initials: C
authors.lastname: Workman
authors.forename: Mark
authors.initials: M
authors.lastname: Bloch
authors.forename: Jacob
authors.initials: J
authors.lastname: Lalezari
authors.forename: Stephen
authors.initials: S
authors.lastname: Becker
authors.forename: Lorna
authors.initials: L
authors.lastname: Thornton
authors.forename: Bisher
authors.initials: B
authors.lastname: Akil
authors.forename: Homayoon
authors.initials: H
authors.lastname: Khanlou
authors.forename: Robert
authors.initials: R
authors.lastname: Finlayson
authors.forename: Robert
authors.initials: R
authors.lastname: McFarlane
authors.forename: Don E
authors.initials: DE
authors.lastname: Smith
authors.forename: Roger
authors.initials: R
authors.lastname: Garsia
authors.forename: David
authors.initials: D
authors.lastname: Ma
authors.forename: Matthew
authors.initials: M
authors.lastname: Law
authors.forename: John M
authors.initials: JM
authors.lastname: Murray
authors.forename: Christof
authors.initials: C
authors.lastname: von Kalle
authors.forename: Julie A
authors.initials: JA
authors.lastname: Ely
authors.forename: Sharon M
authors.initials: SM
authors.lastname: Patino
authors.forename: Alison E
authors.initials: AE
authors.lastname: Knop
authors.forename: Philip
authors.initials: P
authors.lastname: Wong
authors.forename: Alison V
authors.initials: AV
authors.lastname: Todd
authors.forename: Margaret
authors.initials: M
authors.lastname: Haughton
authors.forename: Caroline
authors.initials: C
authors.lastname: Fuery
authors.forename: Janet L
authors.initials: JL
authors.lastname: Macpherson
authors.forename: Geoff P
authors.initials: GP
authors.lastname: Symonds
authors.forename: Louise A
authors.initials: LA
authors.lastname: Evans
authors.forename: Susan M
authors.initials: SM
authors.lastname: Pond
authors.forename: David A
authors.initials: DA
authors.lastname: Cooper
mesh_terms: 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
chemical_list: D018952:Antigens, CD34; D010919:Placebos; D016337:RNA, Catalytic