Clinical trial NCT03980691: Effect of Chidamide Combined With CAT-T or TCR-T Cell Therapy on HIV-1 Latent Reservoir
Official title: Effect of Chidamide Combined With CAT-T or TCR-T Cell Therapy on HIV-1 Latent Reservoir
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: HIV/AIDS
Keywords: Chidamide,CAR cell therapy,TCR cell therapy
Lead sponsor: Guangzhou 8th People's Hospital
Sponsor class: OTHER
Collaborators: name: Sun Yat-sen University
First posted: 2019-06-10
Enrollment: 4
Sex: ALL
Minimum age (years): 18
Maximum age (years): 60
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention 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.
Primary purpose: TREATMENT

Brief summary: 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: 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.

Eligibility criteria: Inclusion Criteria:

1. HIV infection confirmed
2. Receiving cART more than 12 months.
3. HIV viral-load \< 50 copies/ml and CD4 cell count more than 350 cells/ul.
4. Without serious liver , heart, liver and kidney diseases.
5. The subjects know about the study and volunteer to attend the research and sign the informed consent.

Exclusion Criteria:

1. With active HBV or HCV infection, or serious opportunistic infections.
2. With serious chronic disease such like diabetes, the mental illness,et al
3. History of suffering from pancreatitis during cART .
4. Pregnant or breast-fed.
5. With poor adherence.
6. Unable to complete follow up.

Primary outcomes:
measure: Incidence of treatment-associated adverse events
timeFrame: 6 Months
Secondary outcomes:
measure: HIV reservoir
timeFrame: 6 Months
Other outcomes:
measure: HIV-specific immunity
timeFrame: 6 Months
Locations:
city: Guangzhou
country: China
facility: Guangzhou 8th People's Hospital
state: Guangdong
Study officials:
affiliation: Guangzhou 8th People's Hospital China, Guangdong
name: Weiping Cai, Bachelor
role: PRINCIPAL_INVESTIGATOR
References:
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citation: Kuai Q, Lu X, Qiao Z, Wang R, Wang Y, Ye S, He M, Wang Y, Zhang T, Wu H, Ren S, Yu Q. Histone deacetylase inhibitor chidamide promotes reactivation of latent human immunodeficiency virus by introducing histone acetylation. J Med Virol. 2018 Sep;90(9):1478-1485. doi: 10.1002/jmv.25207. Epub 2018 May 25.
citation: Yang W, Sun Z, Hua C, Wang Q, Xu W, Deng Q, Pan Y, Lu L, Jiang S. Chidamide, a histone deacetylase inhibitor-based anticancer drug, effectively reactivates latent HIV-1 provirus. Microbes Infect. 2018 Oct-Nov;20(9-10):626-634. doi: 10.1016/j.micinf.2017.10.003. Epub 2017 Nov 8.
citation: Kobayashi Y, Gelinas C, Dougherty JP. Histone deacetylase inhibitors containing a benzamide functional group and a pyridyl cap are preferentially effective human immunodeficiency virus-1 latency-reversing agents in primary resting CD4+ T cells. J Gen Virol. 2017 Apr;98(4):799-809. doi: 10.1099/jgv.0.000716. Epub 2017 Apr 27.
citation: Liu B, Zou F, Lu L, Chen C, He D, Zhang X, Tang X, Liu C, Li L, Zhang H. Chimeric Antigen Receptor T Cells Guided by the Single-Chain Fv of a Broadly Neutralizing Antibody Specifically and Effectively Eradicate Virus Reactivated from Latency in CD4+ T Lymphocytes Isolated from HIV-1-Infected Individuals Receiving Suppressive Combined Antiretroviral Therapy. J Virol. 2016 Oct 14;90(21):9712-9724. doi: 10.1128/JVI.00852-16. Print 2016 Nov 1.