Study of Autologous T-cells Genetically Modified at the CCR5 Gene by Zinc Finger Nucleases in HIV-Infected Subjects

Laboratory studies have shown that when CD4+ T-cells are modified with Zinc Finger Nucleases SB-728, HIV is prevented from killing the CD4+ T-cells. On the basis of these laboratory results, there is the potential that this may work in humans infected with HIV and improve their immune system by allowing their CD4+ T-cells to survive longer.

The new treatment to be studied will involve removing white blood cells from the blood that contain CD4+ T-cells. The extracted CD4+ T-cells are then genetically modified by the Zinc finger Nucleases to be resistant to infection by removing the CCR5 gene from the surface of the CD4+ T-cell where HIV enters the cell. Additional genetically modified cells are manufactured and then re-infused back into the individual. Researchers hope that these genetically modified cells will be resistant to infection by HIV and will be able to reproduce additional resistant CD4+ T-cells in your body.

Inclusion criteria

• Documented HIV infection
• CD4+ T-cell count >500 cell per millimeter cubed (cells/mm3)
• CD4+ T-cell nadir of >400 cells/mm3
• HIV viral load >1,000 copies per milliliter (mL)

Exclusion criteria

• Any viral hepatitis
• Acute HIV infection
• HIV viral load >1,000,000 copies/mL
• Active or recent (prior 6 months) AIDS defining complication
• Any HIV medications within the past 12 weeks
• Cancer or malignancy that has not been in remission for at least 5 years with the exception of successfully treated basal cell carcinoma of the skin
• Current diagnosis of NYHA grade 3 or 4 congestive heart failure or uncontrolled angina or arrhythmias
• History of bleeding problems
• Use of chronic steroids in past 30 days
• Pregnant or breast feeding
• Active drug or alcohol abuse
• Serious illness in past 30 days
• Currently participating in another clinical trail or any prior gene therapy