'Major Advance' in HIV Gene Therapy

Study Shows HIV Gene Therapy Is Safe, Could Make Body Resist AIDS Virus

Medically Reviewed by Louise Chang, MD on February 16, 2009
From the WebMD Archives

Feb. 16, 2009 -- A one-time gene therapy that puts an anti-HIV RNA weapon into blood cells is safe and, in higher doses and stronger form, could make the body resist the AIDS virus, a clinical trial suggests.

This "major advance in the field" is the largest clinical trial ever to test genetically altered cells in humans, say UCLA researcher Ronald T. Mitsuyasu, MD, and colleagues.

"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," the researchers report in the Feb. 15 advance online issue of Nature Medicine.

The treatment calls for patients to get shots of a growth factor that stimulates growth of white blood cells. Then the cells are taken from their blood. Blood stem cells are separated out and put in cell culture dishes.

In the culture, the patients' own blood stem cells are infected with OZ1, a genetically engineered mouse virus that gives them an anti-HIV gene. This gene encodes an RNA molecule called a ribozyme, which specifically targets and inactivates HIV genes.

Once equipped with the anti-HIV gene, the blood stem cells are transfused back into the patient. The idea is for these stem cells to home in to the bone marrow and populate it with HIV-resistant T cells. As the older T cells die off or are killed by HIV, more and more of the body's T cells should be HIV resistant.

In this phase II clinical trial, 74 patients got infusions -- 38 with OZ1-equipped stem cells and 36 with inactive placebo infusions. All of the patients had HIV infection and had their infections under control with highly active antiretroviral (HAART) drug combinations.

What happened? First and foremost, nobody got hurt. There were no harmful side effects linked to the OZ1 gene therapy in the 100-week study. And there was no sign that HIV developed resistance to the anti-HIV ribozyme encoded in the gene therapy.

And even though doses were kept low, there were anti-HIV effects:

  • Throughout the 100-week trial, patients who received the OZ1 cells had higher numbers of CD4 T cells, the kind of white blood cell that HIV attacks and kills.
  • When patients went off their anti-HIV drugs, those who received the gene therapy were able to postpone restarting treatment longer than those who received a placebo.
  • During treatment interruptions, treated patients had higher CD4 T-cell counts and lower HIV viral load than placebo patients.

Now that researchers have shown this kind of gene therapy can work, future treatments will increase the dose, improve homing to the bone marrow, and carry an even more powerful anti-HIV gene. And in the future, patients would be treated before starting anti-HIV drugs.