Safety Study of Zinc Finger Nuclease CCR5-modified Hematopoietic Stem/Progenitor Cells in HIV-1 Infected Patients

Prior treatment

• Participants may not be receiving any other investigational agents, or concurrent biological, chemotherapy, or radiation therapy. Participation in prior investigational drug or medical device study within the previous 45 days.
• Prior therapy with HIV vaccine or gene therapy product.
• History of alcohol or substance abuse for the previous 12 months.
• Participants with active malignancies. However, participants with skin cancers, namely basal cell or squamous cell carcinoma, and malignancies treated with curative intent having no known active disease present for ≥2 years, may be eligible.

Other illness

• History of significant hematologic diseases such as leukemia, myelodysplasia, coagulopathy, and thromboembolism.
• Any AIDS-related opportunistic infection occurring within the past year such as tuberculosis, cryptococcosis and for which treatment has been unsuccessful as determined by the Principal Investigator.
• AIDS-related syndromes, infectious or otherwise, if perceived to cause excessive risk for morbidity post-HSPC infusion, as determined by the Principal Investigator.
• Patients with active HBV or HCV infection, i.e., HBV DNA and HCV RNA in blood, are excluded. Those with inactive, but past infection with HBV (positive HBV surface antigen or HBV surface antibody) or inactive HCV (positive HCV antibody), must have no cirrhosis, as determined by abdominal ultrasound with elastography.
• Any history of HIV-associated encephalopathy; dementia of any kind; seizures in the past 12 months; any perceived inability to directly provide informed consent.
• Current or history of immunomodulatory agent or steroid use.

Other

• Use of AZT or maraviroc in the cART regimen.
• Active CMV retinitis or other active CMV-related organ dysfunction.
• CXCR4-tropic virus.
• Pregnant or nursing women.

• Maximum age 75 years for cohort 1 and 65 years for cohort 2.
• HIV-1 R5 seropositive with no evidence of CXCR4-tropic virus.
• On cART with undetectable HIV-1 (\<20 gc/ml HIV-1 RNA) for at least 12 months prior to screening evaluations.
• CD4+ T-cell counts ≥200 cells/µL and ≤750 cells/µL.
• No psychosocial conditions that would hinder study compliance and follow-up.
• Absence of clinically significant cardiomyopathy, congestive heart failure.
  • Secondary Eligibility Criteria (for registration):
• Complete G-CSF/Plerixafor mobilization of HSPC.
• Collect ≥7.5 x 10\^6 CD34+ cells/kg in two aphereses.
• The SB-728mR-HSPC product passed all release testing