AIDS, HIV Infections
Conditions
Keywords
HIV, AIDS, Lentivirus, shRNA, Multiplex, Gene therapy
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.
Interventions
BIOLOGICALshRNA-modified CD34+ cells
Infusion of CD34+ cells transduced with shRNAs.
DRUGLow dose busulfan preconditioning
A single dose of 1 mg/kg busulfan administered every 6 hours for 4 times as preconditioning for transplantation.
DRUGBusulfan preconditioning
A single dose of 1 mg/kg busulfan administered every 6 hours for 8 times as preconditioning for transplantation.
Sponsors
R&D Kanglin Biotech
Shanghai Public Health Clinical Center
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
Infusion of autologous CD34+ cells transduced with shRNAs targeting CCR5 and HIV genome
Eligibility
Sex/Gender
ALL
Age
18 Years to 50 Years
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Adverse side effects | 18 months | Patients will be monitored for any signs of adverse effects. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Efficacy of treatment | 18 months | Evaluate the efficacy of modified autologous CD34+ cells by monitoring CD4 counts and HIV-1 RNA level. |
Countries
China
Contacts
Primary ContactHongzhou Lu, M.D., Ph.D
Backup ContactLi Liu, M.D., Ph.D
Outcome results
None listed