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

Inclusion criteria

• Documented HIV infection prior to study entry
• Must be willing to comply with study-mandated evaluations; including not changing their antiretroviral regimen (unless medically indicated) during the study period.

Cohort 1, 2 and 3 (Enrollment Completed)

Cohort 5:

• Must have received HAART therapy, and had undetectable viral loads for at least 1 year.
• HIV-1 RNA < 50 copies/mL obtained within 60 days prior to study entry performed with an ultrasensitive HIV-1 PCR assay.
• CD4+ T cell count >500 cells/mm3
• Heterozygous for the CCR5 delta-32 mutation
• On stable antiretroviral medication (no changes to treatment within 4 weeks of screening and willing to discontinue current antiretroviral therapy during the structured therapy interruption

Cohort 4

• On stable antiretroviral medication (no changes to treatment within 4 weeks of screening and willing to continue on current antiretroviral therapy through week 8 after infusion
• CD4+ T cell count >350 cells/mm3.
• HIV-1 >1,000 copies/mL at screen and not responding to current antiviral therapy (i.e. HIV-RNA plasma levels > 1000 copies/ml after at least 12 weeks of stable, unchanged ARV therapy).

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