Third-Generation CAR-T-cell Therapy in Individuals With HIV-1 Infection

Study Overview
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Brief Summary
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To evaluate the safety of autologous CAR-T-cell therapy in individuals lived with HIV-1 infection, CAR T cells are infused after ex vivo expansion and transduction with lentiviral vectors encoding a broadly neutralizing HIV-1 scFv antibody.

Detailed Description
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This study is a prospective, single-center, single-arm, open-label and phase I clinical trial. Subjects with CD4+T cell counts greater than 350/μl and viral loads of <50 copies/ml over 1 year by antiviral treatment are enrolled. T cells are stimulated with CD3 and CD28, transduced with lentiviral vectors encoding a broadly neutralizing HIV-1 scFv antibody and expanded for approximately 2 weeks. Then, patients are infused with CAR T cells at a dosage of 1×10^5 CAR-T cells/kg body weight. If this dose is well tolerated, dosing will be increased to 5×10^5 CAR T cells/kg body weight. After infusion, adverse events, and HIV-1 latent reservoir size and CAR levels in peripheral blood will be monitored to assess the safety of CAR-T-cell treatment, potential therapeutic efficacy and kinetics of CAR T cells.

Official Title
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A Phase I Trial Using Third-Generation CAR-T-cell Therapy in Individuals With HIV-1 Infection

Conditions
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HIV-1

Intervention / Treatment
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* Biological: CAR-T cells


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Aged 18 to 70 years HIV-1 infection by confirmed test; Receiving antiviral treatment ≥ 1 years; Current CD4+ T cell count > 350 cells/μl; HIV-1 RNA levels of < 50 copies/ml for at least a year; Patients who agrees to use two effective methods of contraception to avoid pregnancy during the study period. Patients who sign the informed consent form prior to inclusion in the study. Exclusion Criteria: Patients with concomitant HAV, HBV, HCV, HDV, HEV, EBV, CMV or syphilis infection; A history of AIDS-related opportunistic infections and tumors within 1 year prior to enrollment; A History of corticosteroids or immunosuppressive drugs for autoimmune diseases by physicians within the last 2 years; Participants with clinically significant laboratory abnormalities as follows: Hemoglobin ≤ 10 gm/dl (female), <11g/dl (male) Absolute neutrophil count ≤ 1×10^9/L Platelet count ≤100×10^9/L Alanine aminotransferase (ALT)≥ 2.5 x ULN Aspartate aminotransferase (AST) ≥ 2.5 x ULN Total bilirubin > 1.5 ULN Serum creatinine >110 μmol/L International normalized ratio (INR) >1.5 or activated partial thromboplastin time (APTT) >45 s Patients with severe psychiatric illness, drugs or alcohol abuse; A woman who is in pregnancy or lactation; A history of central nervous system disease, such as cerebral hemorrhage, dementia, epilepsy and autoimmune diseases; Patients with a non-AIDS-related serious underlying disease; Patients who participate in another clinical study currently which may affect the results of this study.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: CAR-T-cell therapy<br>Four patients with plasma HIV RNA <50 copies/ml and CD4+T cell count more than 350 cells/μl receiving at least one-year antiviral treatment are injected intravenously with 1×10^5 CAR-T cells/kg body weight. If the dosage of 1×10^5 CAR-T cells/kg body weight is well tolerated, 5×10^5 CAR-T cells/kg body weight will be infused for another 4 subjects who meet the inclusion and exclusion criteria. | Biological: CAR-T cells<br>* The presence of latent infected cells remains a key barrier to HIV-1 functional cure. Current approach to reducing the latent HIV reservoir is to reactivate virus-containing cells to make them be detected and eliminated by host defense. Endogenous cytotoxic T-lymphocytes (CTL) may not be adequate because of cellular exhaustion and immune escape of virus. We have designed a kind of CAR-T cell based on CTL engineered to express a scFv of a broadly neutralizing anti-HIV antibody. According to our preclinical studies, CAR-T cells strongly eradicated HIV-1-infected target cells making them a particularly suitable candidate to reach a functional HIV cure. In this clinical trial, we mainly intend to evaluate the safety of CAR-T-Cell therapy on HIV patients whose plasma HIV has been successfully suppressed after antiviral therapy.<br>* Other names: HIV-1 specific chimeric antigen receptor T cells;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Evaluation the safety of CAR-T-cell treatment | To assess the adverse events of CAR-T-cell therapy in HIV-1 infected individuals by measuring liver function, blood routine, and cytokine and so on in this clinical trial | 3 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Assessment the potential therapeutic efficacy of CAR-T cell therapy | To evaluate the change of HIV-1 latent reservoir in peripheral blood after CAR-T-cell therapy by RT-PCR | 3 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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CAR T cells, HIV-1 infection, safety, HIV latent reservoir