An Efficacy and Safety Study of shRNA-modified CD34+ Cells in HIV-infected Patients.
Phase 1
- Conditions
- HIV InfectionsAIDS
- Interventions
- Biological: shRNA-modified CD34+ cellsDrug: Low dose busulfan preconditioning
- Registration Number
- NCT03517631
- Lead Sponsor
- Shanghai Public Health Clinical Center
- Brief Summary
The purpose of the study is to evaluate the efficacy and safety of autologous CD34+ cells that stably express multiplexed shRNA to treat HIV infection.
- Detailed Description
CD34+ cells will be isolated from mobilized PBMC of HIV patients. The cells will be lentivirally transduced with multiplexed shRNAs in the same vector that target CCR5 and HIV genome. Such modified cells will be infused back to the patients who have received bulsufan preconditioning before infusion. The patients will then be evaluated for efficacy and safety.
Recruitment & Eligibility
- Status
- UNKNOWN
- Sex
- All
- Target Recruitment
- 6
Inclusion Criteria
- Body mass index (BMI) from 18 - 25; body weight ≥50kg.
- Diagnosis of HIV infections/AIDS based on "Diagnostic Criteria for HIV/AIDS" WS 293-2008.
- No antiretroviral therapy (ART) in the past 6 weeks and refuse to receive ART.
- CD4 T cell count ≥350/μl.
- No plan for pregnancy in the near future and agree to practice non-drug based contraception.
- Voluntary to participate in the study, comply with the study design to complete all monitory measurements, and agree to sign the study agreement.
Exclusion Criteria
- Existence of infections/opportunistic tumors.
- Mutations in the shRNA target sequences.
- White blood cell count <3x10^9/L, neutrophil count <1.5x10^9/L, hemoglobin <110g/L, platelet count <100x10^9/L.
- Liver diseases (HBV, chronic HCV infection, congenital liver metabolic disease), abnormal liver functions (test value 2x above normal).
- Kidney deficiency (Creatinine level above the upper limit of normal levels).
- Severe chronic disease, metabolic disease (e.g., diabetes), neurological and psychiatric diseases.
- History of pancreatitis.
- Women in pregnancy, lactating or at reproductive age who do not practice contraception.
- Allergy to agents or drugs used in the study.
- Verified or suspected abuse of alcohol and drugs.
- Participated in other clinical trials within 3 months.
- Based on investigator's assessment, those who are unfit for the study (e.g., general weakness, poor compliance with study design).
- Personal or family history of tumors.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Low dose busulfan preconditioning shRNA-modified CD34+ cells shRNA-modified CD34+ cells, with a single dose of 1 mg/kg busulfan administered every 6 hours for 4 times as preconditioning for transplantation. High dose busulfan preconditioning shRNA-modified CD34+ cells shRNA-modified CD34+ cells, with a single dose of 1 mg/kg busulfan administered every 6 hours for 8 times as preconditioning for transplantation. High dose busulfan preconditioning Busulfan preconditioning shRNA-modified CD34+ cells, with a single dose of 1 mg/kg busulfan administered every 6 hours for 8 times as preconditioning for transplantation. No busulfan preconditioning shRNA-modified CD34+ cells shRNA-modified CD34+ cells without busulfan preconditioning. Low dose busulfan preconditioning Low dose busulfan preconditioning shRNA-modified CD34+ cells, with a single dose of 1 mg/kg busulfan administered every 6 hours for 4 times as preconditioning for transplantation.
- Primary Outcome Measures
Name Time Method Adverse side effects 18 months Patients will be monitored for any signs of adverse effects.
- Secondary Outcome Measures
Name Time Method Efficacy of treatment 18 months Evaluate the efficacy of modified autologous CD34+ cells by monitoring CD4 counts and HIV-1 RNA level.
Trial Locations
- Locations (1)
Shanghai Public Health Clinical Center
🇨🇳Shanghai, Shanghai, China