Article abstract

Nature Medicine 15, 285 - 292 (2009)
Published online: 15 February 2009 | doi:10.1038/nm.1932

Phase 2 gene therapy trial of an anti-HIV ribozyme in autologous CD34+ cells

Ronald T Mitsuyasu1, Thomas C Merigan2, Andrew Carr3, Jerome A Zack4, Mark A Winters2, Cassy Workman5, Mark Bloch6, Jacob Lalezari7, Stephen Becker8, Lorna Thornton8, Bisher Akil9, Homayoon Khanlou10, Robert Finlayson11, Robert McFarlane12, Don E Smith13, Roger Garsia14, David Ma3, Matthew Law15, John M Murray15,16, Christof von Kalle17,18, Julie A Ely19, Sharon M Patino19, Alison E Knop19, Philip Wong19, Alison V Todd19, Margaret Haughton19, Caroline Fuery19, Janet L Macpherson19, Geoff P Symonds19, Louise A Evans19, Susan M Pond19 & David A Cooper3,15

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.

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  1. Center for Clinical AIDS Research and Education, University of California–Los Angeles, 9911 West Pico Boulevard, Suite 980, Los Angeles, California 90035, USA.
  2. Division of Infectious Diseases and Geographic Medicine, Stanford University, 300 Pasteur Drive, Stanford, California 94305, USA.
  3. St. Vincent's Hospital, 406 Victoria Road, Darlinghurst, New South Wales 2010, Australia.
  4. Department of Medicine and Microbiology, University of California–Los Angeles, 405 Hilgard Avenue, Los Angeles, California 90095, USA.
  5. AIDS Research Initiative, 48 Little Oxford Street, Darlinghurst, New South Wales 2010, Australia.
  6. Holdsworth House Medical Practice, Suite 3/32a Oxford Street, Darlinghurst, New South Wales 2010, Australia.
  7. Quest Clinical Research, 2300 Sutter Street, San Francisco, California 94115, USA.
  8. Pacific Horizon Medical Group, 2351 Clay Street, San Francisco, California 94115, USA.
  9. Health Innovations Research, 9201 Sunset Bouldevard, Los Angeles, California 90069, USA.
  10. AIDS Healthcare Foundation Research Center, 6255 West Sunset Boulevard, Los Angeles, California 90028, USA.
  11. Taylor Square Private Clinic, 393 Bourke Street, Darlinghurst, New South Wales 2010, Australia.
  12. East Sydney Doctors, 102 Burton Street, Darlinghurst, New South Wales 2010, Australia.
  13. Albion Street Centre, 150 Albion Street, Darlinghurst, New South Wales 2010, Australia.
  14. Royal Prince Alfred Hospital, Missenden Road, Camperdown New South Wales 2050, Australia.
  15. National Centre in HIV Epidemiology and Clinical Research, 376 Victoria Street, Darlinghurst, University of New South Wales, New South Wales 2010, Australia.
  16. School of Mathematics and Statistics, University of New South Wales, Randwick, New South Wales 2052, Australia.
  17. Cincinnati Children's Hospital Research Foundation, 3333 Burnet Avenue, Cincinnati, Ohio 45229-3039, USA.
  18. National Center for Tumor Diseases, German Cancer Research Center, Neuenheimer Feld 350, Heidelberg 69120, Germany.
  19. Johnson & Johnson Research Proprietary Limited, 1 Central Avenue, Australian Technology Park, Eveleigh, Sydney, New South Wales 1430, Australia.

Correspondence to: Ronald T Mitsuyasu1 e-mail: rmitsuya@mednet.ucla.edu



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