Phase 1 Dose Escalation Study of Autologous T-cells Genetically Modified at the CCR5 Gene by Zinc Finger Nucleases in HIV-Infected Patients

Exclusion Criteria

• •Acute or chronic hepatitis B or hepatitis C infection
• •Active or recent (in prior 6 months) AIDS defining complication.
• •Any cancer or malignancy within the past 5 years, with the exception of successfully treated basal cell or squamous cell carcinoma of the skin or low grade (0 or 1) anal or cervical dysplasia.
• •Current diagnosis of NYHA grade 3 or 4 CHF, uncontrolled angina or uncontrolled arrhythmias.
• •History or any features on physical examination indicative of a bleeding diathesis.
• •Previous treatment with any HIV experimental vaccine within 6 months prior to screening, or any previous gene therapy using an integrating vector.
• •Use of chronic corticosteroids, hydroxyurea, or immunomodulating agents (e.g., interleukin-2, interferon-alpha or gamma, granulocyte colony stimulating factors, etc.) within 30 days prior to enrollment
• •Breast-feeding, pregnant or unwilling to use acceptable methods of birth control for 6 months following the last infusion of SB-728-T cells.
• •warfarin or any other medication that is likely to affect platelet function or other aspects of blood coagulation during the 2 week period prior to leukapheresis.
• •Active drug or alcohol use or dependence
• •Serious illness requiring systemic treatment and/or hospitalization within 30 days prior to study entry.
• •Recent vaccination or intercurrent illness (within 5 weeks prior to infusion)
• •Have an allergy or hypersensitivity to study product excipients (human serum albumin, DMSO and Dextran 40).
• •Subjects who are currently taking maraviroc or have received maraviroc within 6 months prior to screening.
• •Cohort 4 only:
• •HIV-1 RNA \>1,000 copies/mL at screen and not responding to current antiviral therapy
• •CD4+ T cell count \>350 cells/mm3