Cell-Delivered Gene Therapy Shows Promise as Treatment for AIDS

Results of a phase II clinical trial indicated that cell-delivered gene therapy has potential as a treatment method for AIDS.

Investigators from the University of California, Los Angeles (USA) reported in the February 15, 2009, online edition of the journal Nature Medicine that they had conducted a randomized, double-blind, placebo-controlled, phase II cell-delivered gene transfer clinical trial, on 74 HIV-1-infected adults. The subjects were treated with a tat-vpr–specific anti-HIV ribozyme (OZ1) or a placebo delivered in autologous CD34+ hematopoietic progenitor cells. In other words, each patient received a treated version of his own immune cells, either carrying a molecule called OZ1 or a placebo. OZ1 prevents viral replication by targeting a key HIV gene.

Results showed that although there was not a significant difference in viral load between the two groups, other viral parameters did demonstrate better HIV suppression and improvement in the counts of CD4+ lymphocytes in the OZ1-treated group. Over the 100 weeks of the study, no toxic effects of OZ1 were found.

"It is the first randomized controlled study done with gene therapy in HIV,” said first author Dr. Ronald Mitsuyasu, professor of medicine at the University of California, Los Angeles. "What we were able to demonstrate was that the patients who received the gene-modified cells had a somewhat better suppression of their HIV viral replication after discontinuing their highly active antiretroviral therapy [HAART] treatment, compared with the controls. Part of the reason that we did not see a larger effect is that the persistence of the anti-HIV gene in the patient's blood was not as long as we would have liked. We need to find better ways to get the genes into the patients and maintain them, which could include using different vectors to get the gene into the cells or conditioning the patients prior to gene transfer.”

The investigators believe that the bottom line is that cell-delivered gene transfer is safe and biologically active in individuals with HIV and can be developed as conventional therapeutic product.

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