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

HIV/AIDS Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03980691
• Other study ID #: 20171126V1
• Status: Completed
• Phase: Phase 1
• Start date: December 1, 2017
• Est. completion date: May 31, 2020

Study information

• Verified date: July 2021
• Source: Guangzhou 8th People's Hospital
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 4
• Est. completion date: May 31, 2020
• Est. primary completion date: May 31, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 60 Years

Eligibility

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.

Related Conditions & MeSH terms

• Acquired Immunodeficiency Syndrome
• HIV Infections
• HIV/AIDS

Intervention

Biological:
• Chidamide with CAR-T or TCR-T cell therapy
HIV-1 specific therapy

Locations

Country	Name	City	State
China	Guangzhou 8th People's Hospital	Guangzhou	Guangdong

Sponsors (2)

Lead Sponsor	Collaborator
Guangzhou 8th People's Hospital	Sun Yat-sen University

Country where clinical trial is conducted

China, 

References & Publications (6)

Dotti G, Gottschalk S, Savoldo B, Brenner MK. Design and development of therapies using chimeric antigen receptor-expressing T cells. Immunol Rev. 2014 Jan;257(1):107-26. doi: 10.1111/imr.12131. Review. — View Citation

Kobayashi Y, Gélinas 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. — View 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. — View 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 Lym — View Citation

Liu C, Ma X, Liu B, Chen C, Zhang H. HIV-1 functional cure: will the dream come true? BMC Med. 2015 Nov 20;13:284. doi: 10.1186/s12916-015-0517-y. Review. — View 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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	HIV-specific immunity	The number of HIV-specific CD4,CD8,VC-CAR-T and TCR-T cells after receiving the therapy.	6 Months
Primary	Incidence of treatment-associated adverse events	To observe the adverse events of intervention n HIV-infected patients during the study.	6 Months
Secondary	HIV reservoir	To assay the HIV loads in the peripheral blood Mono-nuclear cells and plasma	6 Months