Redirected MazF-CD4 Autologous T Cells for HIV Gene Therapy

Inclusion Criteria

• •1. HIV-1 infection, as documented by a rapid HIV test or any FDA-approved HIV-1 enzyme or chemiluminescence immunoassay (E/CIA) test kit and confirmed by Western blot at any time prior to study entry. Alternatively, if a rapid HIV test or any FDA-approved HIV-1 enzyme or chemiluminescence immunoassay (E/CIA) test kit is not available, two HIV-1 RNA values \>2000 copies/mL at least 24 hours apart performed by any laboratory that has CLIA certification, or its equivalent, may be used to document infection.
• •2. Antiretroviral medication
• •* Cohort 1: Subjects on HAART (no changes to treatment within 4 weeks of study entry) for at least 3 months.
• •* Subjects on HAART (no changes to treatment within 4 weeks of study entry) for at least 3 months.
• •3. Plasma HIV viremia
• •* Cohort 1: HIV-1-positive men and women \>18 years of age with HIV-1-RNA levels undetectable by ultrasensitive HIV PCR Abbott assay at screening. Also eligible are subjects with HIV-1 RNA \< 400 copies/mL; however, the HIV-1 RNA must be \< 50 copies/mL within 60 days prior to study entry based on the Abbott assay. Subjects with intermittent isolated episodes of detectable low level viremia (\> 50 but \<1,000 copies RNA/mL; blips) will be eligible. There should be at least 2 documented HIV-1 RNA assays, one drawn \>3 months before study entry, one drawn \<3 months before study entry.
• •* Cohort 2: HIV-1-positive men and women \>18 years of age with HIV-1-RNA levels undetectable by ultrasensitive HIV PCR assay at screening. Note: Due to sensitivity issues using the Roche Assay and the fact that we cannot control the HIV testing technique prior to enrollment, we decided to consider subjects with HIV-1 RNA \< 400 copies/mL; however, the HIV-1 RNA must be undetectable within 60 days prior to study entry based on the ultrasensitive HIV PCR assay. Subjects with intermittent isolated episodes of detectable low level viremia (\> 50 but \<1,000 copies RNA/mL; blips) will be eligible. There should be at least 2 documented HIV-1 RNA assays: one drawn \>3 months before study entry, one drawn \<3 months before study entry.
• •4. CD4 counts
• •* Cohort 1: Subjects with CD4 counts \>350 cells/mm3.
• •* Cohort 2: Subjects with CD4 counts of at least 450 cells/mm3 at screening. Note: CD4 nadir in Cohort 2 must be above 200 cells/mm3.
• •5. Adequate venous access and no other contraindications for leukapheresis.
• •6. Laboratory values obtained within 60 days prior to entry.
• •* Hemoglobin: ≥ 10.0 (males); ≥ 9.5 (females) g/dL
• •* Absolute neutrophil count (ANC): ≥ 1000/mm3
• •* Platelet count: ≥ 75,000/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).
• •7. Subjects must be willing to comply with study-mandated evaluations. Rectal biopsy procedures are optional.
• •8. Be male or female, 18 years of age and older.
• •9. Ability and willingness of subject to provide informed consent.
• •10. Have a Karnofsky Performance Score of 70 or higher.