Effect of Chidamide Combined With CAT-T or TCR-T Cell Therapy on HIV-1 Latent Reservoir

Study Overview
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Brief Summary
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To study the safety and effectiveness of the combination of Chidamide with Chimeric Antigen Receptor(CAR)-T or T cell receptor(TCR)-T cell therapy on HIV patients based on cART.

Detailed Description
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Despite the advent of combined antiretroviral therapy (cART), the persistence of viral reservoirs remains a major barrier to cure human immunodeficiency virus type 1 (HIV-1) infection. Recently, the shock and kill strategy, by which such reservoirs are eradicated following reactivation of latent HIV-1 by latency-reversing agents (LRAs), has been extensively practiced. It is important to reestablish virus-specific and reliable immune surveillance to eradicate the reactivated virus-harboring cells. Some studies have shown that Chidamide can highly activate the HIV reservoirs. The VC-CAR-T cells effectively induced the cytolysis of LRA-reactivated HIV-1-infected CD4 T lymphocytes isolated from infected individuals receiving suppressive cART. Our previous study demonstrated that the special features of genetically engineered CAR-T cells make them a particularly suitable candidate for therapeutic application in efforts to reach a functional HIV cure. The purpose of this study is to evaluate the safety and efficacy of Chidamide together with Chimeric Antigen Receptor(CAR)-T or T cell receptor(TCR)-T cell therapy based on cART in HIV-infected adults whose plasma HIV has been successfully suppressed after cART.

Official Title
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Effect of Chidamide Combined With CAT-T or TCR-T Cell Therapy on HIV-1 Latent Reservoir

Conditions
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HIV/AIDS

Intervention / Treatment
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* Biological: Chidamide with CAR-T or TCR-T cell therapy


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: HIV infection confirmed Receiving cART more than 12 months. HIV viral-load < 50 copies/ml and CD4 cell count more than 350 cells/ul. Without serious liver , heart, liver and kidney diseases. The subjects know about the study and volunteer to attend the research and sign the informed consent. Exclusion Criteria: With active HBV or HCV infection, or serious opportunistic infections. With serious chronic disease such like diabetes, the mental illness,et al History of suffering from pancreatitis during cART . Pregnant or breast-fed. With poor adherence. Unable to complete follow up.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 60 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
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: The control arm includes HIV-infected patients without receiving cellar therapy combined with Chidamide whose HIV-1 has been successfully suppressed after cART.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Chidamide combined with CAR-T or TCR-T cell therapy<br>Receiving chidamide combined with CAR-T or TCR-T cell therapy based on based on cART after attaining plasma HIV suppression (plasma HIV RNA <50 cp/ ml) and CD4+ cell count more than 350 cells/ul over 1 year by cART without active HCV or HBV infection or opportunistic infections. | Biological: Chidamide with CAR-T or TCR-T cell therapy<br>* HIV-1 specific therapy<br>|
| No Intervention: without intervention<br>Not receiving chidamide combined with CAR-T or TCR-T cell therapy but continuing cART after attaining plasma HIV suppression (plasma HIV RNA <50 cp/ml) and CD4+ cell count more than 350 cells/ul over 1 year by cART, without active HCV or HBV infection or opportunistic infections. | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of treatment-associated adverse events | To observe the adverse events of intervention n HIV-infected patients during the study. | 6 Months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| HIV reservoir | To assay the HIV loads in the peripheral blood Mono-nuclear cells and plasma | 6 Months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Chidamide,CAR cell therapy,TCR cell therapy