This study aims to investigate the safety and preliminary efficacy of an innovative therapeutic strategy combining chidamide with NKG2D-directed chimeric antigen receptor natural killer (CAR-NK) cells in individuals living with HIV. The approach is predicated on the "shock and kill" paradigm: chidamide is employed to reactivate latent HIV reservoirs and upregulate surface target ligands (NKG2D ligands) on infected cells; subsequently, allogeneic NKG2D CAR-NK cells are infused to specifically recognize and eliminate these "marked" cells.
This is a phase I, open-label, single-arm clinical trial comprising two distinct stages: a dose-escalation phase (phase Ia, utilizing a "1+3+3" design) and a dose-expansion phase (phase Ib). A total of 20 HIV-infected individuals who are stable on antiretroviral therapy (ART) and have suppressed plasma viremia are planned for enrollment. Participants will receive oral chidamide over approximately five weeks, followed by two cycles of intravenous CAR-NK cell infusion.
The primary endpoint is the safety and tolerability of the regimen, with particular attention to immune-related adverse events including cytokine release syndrome (CRS). Secondary endpoints encompass exploratory assessments of potential virologic and immunologic effects, such as alterations in plasma HIV RNA, cell-associated viral nucleic acids, and CD4+ T-cell counts. This study is intended to provide initial human safety data and preliminary evidence regarding the potential of this combination strategy to contribute toward a functional cure for HIV infection.
Diagnosis of HIV infection, with a current history of highly active antiretroviral therapy (HAART) for a minimum duration of two years.
Age between 18 and 65 years, inclusive.
Plasma HIV RNA level < 50 copies/mL (virologic suppression).
CD4⁺ T cell count > 200 cells/μL.
Presence of severe cardiovascular, respiratory, or hematologic disease; active infectious disease (other than controlled HIV infection); or active malignancy.
Positive serology for hepatitis B surface antigen (HBsAg) or detectable hepatitis C virus RNA (HCV RNA).
Diagnosis of chronic kidney disease (CKD).
History or presence of acute or chronic pancreatitis.
Single group
Chidamide Combined with NKG2D CAR-NK Cell Therapy
DrugAll enrolled participants will receive oral chidamide (10 mg twice weekly) for approximately five weeks. During this period, participants will receive two cycles of intravenous infusion of allogeneic NKG2D CAR-NK cells (each cycle consisting of two consecutive daily infusions, separated by an interval of approximately two weeks). Throughout the treatment course, participants will continue their pre-existing antiretroviral regimen without modification.
Number of Participants with Study Drug-Related Adverse Events Grade 3 or Higher
An adverse event (AE) is defined as any untoward medical occurrence in a patient or clinical investigation participant administered a pharmaceutical product which does not necessarily have a causal relationship with this treatment. The investigator assesses the relationship of each event to the use of the study drug as either having a reasonable possibility or no reasonable possibility. AEs are given a grade from 1-5 with Grade 3 being severe but not life-threatening and requiring hospitalization, Grade 4 being life-threatening requiring immediate intervention and Grade 5 being death related to an AE.
Number of Participants with Study Drug-Related Immune-Related Adverse Events (IRAE)
Assessed using the American Society of Clinical Oncology (ASCO) IRAE management guidelines (which utilizes the NIH CTCAE grading scale) but modified, as applicable, according to the NIH Division of AIDS (DAIDS) (v2.1) AE grading scale
Number of Participants with Adverse Events (AEs) Corresponding to Cytokine Release Syndrome
Adverse Events (AEs) Corresponding to Cytokine Release Syndrome
Changes in the HIV latent reservoir
Dynamic changes in plasma HIV RNA, HIV DNA and HIV cell-associated RNA
Change in T-lymphocyte count
Change from baseline in CD4⁺ and CD8⁺ T-cell counts
Maximum Observed Concentration (Cmax)
Maximum Observed Concentration (Cmax) of CAR-NK
Area Under the Curve (AUCtau)
Area Under the Curve (AUCtau) during the dosing intervals for CAR-NK
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First Affiliated Hospital of Zhejiang University
Lead sponsor
Hangzhou Suxi Biopharmaceutical Co., Ltd.
Collaborator
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