SUMMARYGene 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, the first randomized, double-blind, placebo-controlled, phase II 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 statistical 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 provides the first indication that cell-delivered gene transfer is safe and biologically active in HIV patients and can be developed as a conventional therapeutic product.

The proof of principle results reported here demonstrate safety and feasibility of this type of gene transfer approach. While not specifically tested, T-lymphocytes containing an anti-HIV gene construct may impact on HIV-1 viral load and CD4+ T-lymphocyte count, potentially representing a new therapeutic modality for HIV-1 infection.

An artificial capillary culture/transduction technique has readily attainable from 5 × 10 7 CD8-depleted lymphocytes. been developed for application in a phase I gene therapyIn addition, a sensitive and reliable quantitative competitive clinical trial for HIV. The trial protocol involves isolation of PCR method was developed to assess the levels of trans-CD4 + T-lymphocytes from a genetically matched HIV negaduction before infusion into the recipient. The transduction tive twin, retroviral transduction of equal numbers of cells data suggest that the efficiency of retroviral transduction with the ribozyme therapeutic and control genes, and was affected by the presence of inhibitory factors present expansion in Cellmax artificial capillary modules. Precliniin the virus preparations or generated as a result of the cal studies showed transduction efficiencies in the range transduction process itself. It is hypothesised that the of 3-30%, with preferential expansion of CD4+ lymphomethod of transduction could significantly affect the extent cytes over a culture period of 10-14 days. Over this time of this inhibition, and thus impact on clinical efficacy of period, an average yield of 1.7 × 10 9 lymphocytes was retrovirus mediated gene therapy.

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