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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.