Autologous T-Cells Genetically Modified at the CCR5 Gene by Zinc Finger Nucleases SB-728 for HIV

Inclusion Criteria

• •Cohort 1 Only:
• •Patients who have been on two more HAART regimens and have failed due to resistance or tolerance (no changes to treatment within 4 weeks of study entry), and who have no viable treatment options likely to result in complete viral suppression.
• •CD4+ T cell count of ≥200 cells/mm3
• •HIV-1 RNA ≥2000 copies/mL obtained within 60 days prior to study entry performed with an ultrasensitive HIV-1 PCR assay.
• •Two HIV-1 RNA levels \<150,000 copies/mL obtained within 60 days prior to study entry performed with an ultrasensitive HIV-1 PCR assay. These HIV-1 RNA measurements must be at least 48 hours apart and may include the HIV-1 RNA measurement done at the time of the screening visit.
• •Ongoing treatment with HIV entry inhibitors such as enfurvitide or maraviroc are excluded
• •Cohort 2 Only:
• •On a stable antiretroviral medication (no changes to treatment within 4 weeks of study entry) and be willing to continue on current antiretroviral therapy for the duration of the study until undergoing structured treatment interruption.
• •CD4+ T cell count of ≥450 cells/mm3 at screen; and a documented CD4 nadir of not lower than 300 cells/mm.
• •HIV-1 RNA undetectable by ultrasensitive HIV PCR assay obtained within 60 days prior to study entry performed with an ultrasensitive HIV-1 PCR assay.
• •Cohort 3 only:
• •On a stable antiretroviral medication (no changes to treatment within 4 weeks of study entry) and be willing to continue on current antiretroviral therapy for the duration of the study.
• •CD4+ T cell count that is persistently \<500 cells/mm3 despite at least 2 years of stable HAART and \>200 cells/mm3 at screen
• •Subjects must have received at least 2 continuous years of therapy and have had undetectable viral loads by ultrasensitive assay since 6 months of therapy. Subjects who have had a single viral load blip at any point in this time, or who experience intermittent isolated episodes of detectable low-level viremia (detectable but \<1000 copies RNA/mL; blips) will remain eligible.
• •Subjects who are currently taking maraviroc or have received maraviroc within 6 months of study entry are excluded.
• •Inclusion for Cohort 1, Cohort 2, Cohort 3:
• •HIV-1 infection, as documented by ELISA and confirmed by Western blot at any time prior to study entry. HIV-1 culture, HIV-1 antigen, plasma HIV-1 RNA, or a second antibody test by a method other than ELISA is acceptable as an alternative confirmatory test.
• •Adequate venous access and no other contraindications for leukapheresis.
• •Laboratory values obtained at screen. Hemoglobin: ≥ 10.0 (males); ≥ 9.5 (females) g/dL Absolute neutrophil count (ANC): ≥ 1000/mm3 Platelet count: ≥ 100,000/mm3 Serum creatinine: ≤ 1.5 mg/dL (133µ mol/L) Aspartate aminotransferase (AST) or alanine aminotransferase (ALT): ≤ 2.5 times the upper limit of normal (ULN).
• •Subjects must be willing to comply with study-mandated evaluations; including not changing their antiretroviral regimen (unless medically indicated) for 2 months in step 2 (Cohort 1) or until undergoing structured treatment interruption (Cohort 2).
• •Karnofsky Performance Score of 70 or higher