Cooper DA. Phase 2 gene therapy trial of an anti-HIV ribozyme in autologous CD34(+) cells.A

Cooper DA. 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 the knowledge of Mitsuyasu and colleagues 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.

Editors’ note: Gene therapy, which could prove a long-lived alternate to small molecule antiretroviral therapy, includes a variety of approaches. Ribozymes, used in this Phase II trial, are catalytic RNA molecules that can be engineered to target specific RNA sequences without ‘off target’ effects. These investigators hypothesized that a tat-vpr-specific anti-HIV ribozyme would make immune cell forbears change to produce a pool of mature bone marrow and lymph cells that would be protected from HIV replication. Although the trial did not show efficacy, viral loads were consistently lower in the treated group and there were no safety concerns. These are early days for gene therapy for HIV infection but initial results hold some promise.