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

Top Cited Papers
Open Access
Publisher Website
Google Scholar
Abstract
The first phase 2 gene therapy trial for HIV-1 has shown some promising signs. There's a long way to go before this would be a viable approach in people with HIV—this trial did not show a statistically significant difference in viral load at the primary end point–but other analyses did reveal that the gene therapy seemed to have a modest, but statistically significant, effect at reducing viral load in the treated subjects versus the placebo arm. The study also provides some clues about what to improve in the future. 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.