The Effect of Chimeric Antigen Receptor (CAR)-T Cell Therapy on the Reconstitution of HIV-specific Immune Function

Phase 1

Recruiting

• Conditions: HIV/AIDS
• Interventions: Biological: CAR-T cells

• Registration Number: NCT03240328
• Lead Sponsor: Guangzhou 8th People's Hospital

Brief Summary

To study the safety and effectiveness of CAR-T Cell therapy on HIV patients whose plasma HIV has been successfully suppressed after cART, which is expected to enhance the res-constitution of HIV-specific immune function to assist the eradication of HIV reservoir.

Detailed Description

Despite the advent of combined antiretroviral therapy (cART), the persistence of viral reservoirs remains a major barrier to curing human immunodeficiency virus type 1 (HIV-1) infection. Recently, the shock and kill strategy, by which HIV-1 reservoirs could be 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.the VC-CAR-T cells effectively induced the cytolysis of LRA-reactivated HIV-1-infected CD4 T lymphocytes isolated from infected individuals receiving successful 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. In this clinical trial, we intend to study the safety and effectiveness of CAR-T Cell Therapy on HIV patients whose plasma HIV has been successfully suppressed after cART, by observing the adverse events, HIV-1 reservoir and the immune index.

Study Timeline

• Study First Submitted: 2017-05-21
• Study First Submitted QC: 2017-08-02
• Study First Posted: 2017-08-07
• Study Start: 2017-10-04
• Status Verified: 2022-09
• Last Update Submitted: 2022-09-13
• Last Update Posted: 2022-09-14
• Primary Completion: 2023-12-31
• Study Completion: 2030-12-31

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 40

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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
CAR-T therapy	CAR-T cells	Transfusing CAR-T cells at least 1 million clone every time (once or twice) 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. If the candidates reach the criteria of discontinuing cART, they will stop cART and receive close observation. Once the plasma HIV viral load rebound to over 1000 cp/ml, they will restart cART immediately.

Primary Outcome Measures

Name	Time	Method
Incidence of treatment-associated adverse events of CAR-T cell therapy	6 Months	To observe the adverse events of VC-CAR-T cell therapy on HIV-infected patients during the clinical trial

Secondary Outcome Measures

Name	Time	Method
HIV viral load rebound time	6 months	To assay the HIV viral load rebound period after discontinuing cART
HIV-1 reservoir	6 Months	To assay the HIV loads in the peripheral blood Mono-nuclear cells and plasma

Trial Locations

Locations (1)

Guangzhou 8th People's Hospital; 🇨🇳 Guangzhou, Guangdong, China